Innate and adaptive immunity at mucosal surfaces of the female reproductive tract : stratification and integration of immune protection against the transmission of sexually transmitted infections

This review examines the multiple levels of pre-existing immunity in the upper and lower female reproductive tract. In addition, we highlight the need for further research of innate and adaptive immune protection of mucosal surfaces in the female reproductive tract. Innate mechanisms include the mucus lining, a tight epithelial barrier and the secretion of antimicrobial peptides and cytokines by epithelial and innate immune cells. Stimulation of the innate immune system also serves to bridge the adaptive arm resulting in the generation of pathogen-specific humoral and cell-mediated immunity. Less understood are the multiple components that act in a coordinated way to provide a network of ongoing protection. Innate and adaptive immunity in the human female reproductive tract are influenced by the stage of menstrual cycle and are directly regulated by the sex steroid hormones, progesterone and estradiol. Furthermore, the effect of hormones on immunity is mediated both directly on immune and epithelial cells and indirectly by stimulating growth factor secretion from stromal cells. The goal of this review is to focus on the diverse aspects of the innate and adaptive immune systems that contribute to a unique network of protection throughout the female reproductive tract.

Sex hormone regulation of innate immunity in the female reproductive tract : the role of epithelial cells in balancing reproductive potential with protection against sexually transmitted pathogens

The immune system in the female reproductive tract (FRT) does not mount an attack against HIV or other sexually transmitted infections (STI) with a single endogenously produced microbicide or with a single arm of the immune system. Instead, the body deploys dozens of innate antimicrobials to the secretions of the female reproductive tract. Working together, these antimicrobials along with mucosal antibodies attack many different viral, bacterial and fungal targets. Within the FRT, the unique challenges of protection against sexually transmitted pathogens coupled with the need to sustain the development of an allogeneic fetus have evolved in such a way that sex hormones precisely regulate immune function to accomplish both tasks. The studies presented in this review demonstrate that estradiol and progesterone secreted during the menstrual cycle act both directly and indirectly on epithelial cells and other immune cells in the reproductive tract to modify immune function in a way that is unique to specific sites throughout the FRT. As presented in this review, studies from our laboratory and others demonstrate that the innate immune response is under hormonal control, varies with the stage of the menstrual cycle, and as such is suppressed at mid-cycle to optimize conditions for successful fertilization and pregnancy. In doing so, a window of STI vulnerability is created during which potential pathogens including HIV enter the reproductive tract to infect host targets.

The IL-6 response to Chlamydia from primary reproductive epithelial cells is highly variable and may be involved in differential susceptibility to the immunopathological consequences of chlamydial infection

Background Chlamydia trachomatis infection results in reproductive damage in some women. The process and factors involved in this immunopathology are not well understood. This study aimed to investigate the role of primary human cellular responses to chlamydial stress response proteases and chlamydial infection to further identify the immune processes involved in serious disease sequelae. Results Laboratory cell cultures and primary human reproductive epithelial cultures produced IL-6 in response to chlamydial stress response proteases (CtHtrA and CtTsp), UV inactivated Chlamydia, and live Chlamydia. The magnitude of the IL-6 response varied considerably (up to 1000 pg ml-1) across different primary human reproductive cultures. Thus different levels of IL-6 production by reproductive epithelia may be a determinant in disease outcome. Interestingly, co-culture models with either THP-1 cells or autologous primary human PBMC generally resulted in increased levels of IL-6, except in the case of live Chlamydia where the level of IL-6 was decreased compared to the epithelial cell culture only, suggesting this pathway may be able to be modulated by live Chlamydia. PBMC responses to the stress response proteases (CtTsp and CtHtrA) did not significantly vary for the different participant cohorts. Therefore, these proteases may possess conserved innate PAMPs. MAP kinases appeared to be involved in this IL-6 induction from human cells. Finally, we also demonstrated that IL-6 was induced by these proteins and Chlamydia from mouse primary reproductive cell cultures (BALB/C mice) and mouse laboratory cell models. Conclusions We have demonstrated that IL-6 may be a key factor for the chlamydial disease outcome in humans, given that primary human reproductive epithelial cell culture showed considerable variation in IL-6 response to Chlamydia or chlamydial proteins, and that the presence of live Chlamydia (but not UV killed) during co-culture resulted in a reduced IL-6 response suggesting this response may be moderated by the presence of the organism.

Pattern-based topics for document modelling in information filtering

Many mature term-based or pattern-based approaches have been used in the field of information filtering to generate users’ information needs from a collection of documents. A fundamental assumption for these approaches is that the documents in the collection are all about one topic. However, in reality users’ interests can be diverse and the documents in the collection often involve multiple topics. Topic modelling, such as Latent Dirichlet Allocation (LDA), was proposed to generate statistical models to represent multiple topics in a collection of documents, and this has been widely utilized in the fields of machine learning and information retrieval, etc. But its effectiveness in information filtering has not been so well explored. Patterns are always thought to be more discriminative than single terms for describing documents. However, the enormous amount of discovered patterns hinder them from being effectively and efficiently used in real applications, therefore, selection of the most discriminative and representative patterns from the huge amount of discovered patterns becomes crucial. To deal with the above mentioned limitations and problems, in this paper, a novel information filtering model, Maximum matched Pattern-based Topic Model (MPBTM), is proposed. The main distinctive features of the proposed model include: (1) user information needs are generated in terms of multiple topics; (2) each topic is represented by patterns; (3) patterns are generated from topic models and are organized in terms of their statistical and taxonomic features, and; (4) the most discriminative and representative patterns, called Maximum Matched Patterns, are proposed to estimate the document relevance to the user’s information needs in order to filter out irrelevant documents. Extensive experiments are conducted to evaluate the effectiveness of the proposed model by using the TREC data collection Reuters Corpus Volume 1. The results show that the proposed model significantly outperforms both state-of-the-art term-based models and pattern-based models

Science of winning soccer : emergent pattern-forming dynamics in association football

Quantitative analysis is increasingly being used in team sports to better understand performance in these stylized, delineated, complex social systems. Here we provide a first step toward understanding the pattern-forming dynamics that emerge from collective offensive and defensive behavior in team sports. We propose a novel method of analysis that captures how teams occupy sub-areas of the field as the ball changes location. We used the method to analyze a game of association football (soccer) based upon a hypothesis that local player numerical dominance is key to defensive stability and offensive opportunity. We found that the teams consistently allocated more players than their opponents in sub-areas of play closer to their own goal. This is consistent with a predominantly defensive strategy intended to prevent yielding even a single goal. We also find differences between the two teams' strategies: while both adopted the same distribution of defensive, midfield, and attacking players (a 4:3:3 system of play), one team was significantly more effective both in maintaining defensive and offensive numerical dominance for defensive stability and offensive opportunity. That team indeed won the match with an advantage of one goal (2 to 1) but the analysis shows the advantage in play was more pervasive than the single goal victory would indicate. Our focus on the local dynamics of team collective behavior is distinct from the traditional focus on individual player capability. It supports a broader view in which specific player abilities contribute within the context of the dynamics of multiplayer team coordination and coaching strategy. By applying this complex system analysis to association football, we can understand how players' and teams' strategies result in successful and unsuccessful relationships between teammates and opponents in the area of play.

Detecting news topics from microblogs using sequential pattern mining

This thesis presents a sequential pattern based model (PMM) to detect news topics from a popular microblogging platform, Twitter. PMM captures key topics and measures their importance using pattern properties and Twitter characteristics. This study shows that PMM outperforms traditional term-based models, and can potentially be implemented as a decision support system. The research contributes to news detection and addresses the challenging issue of extracting information from short and noisy text.

School-based youth health nurses and adolescent decision-making concerning reproductive and sexual health advice : how can the law guide healthcare practitioners in this context?

This paper outlines some of the issues faced by School-Based Youth Health Nurses working in Queensland, in relation to the legal principles surrounding the provision of reproductive and sexual health advice. The paper outlines a number of specific issues faced by nurses working within this setting and considers the legal principles underpinning the issues concerning consent and confidentiality. The discussion in this paper demonstrates how the legal principles – which are often viewed as complex and uncertain by nurses working within this field – may be used as a guide to underpin good practice and compliance with the law. Although this paper is considered in the context of nurses working within Queensland, the principles and factors outlined are relevant to healthcare practitioners working within all Australian jurisdictions.

RNA interference silencing of CHS greatly alters the growth pattern of apple (Malus x domestica)

Plants produce a vast array of phenolic compounds which are essential for their survival on land. One major class of polyphenols are the flavonoids and their formation is dependent on the enzyme chalcone synthase (CHS). In a recent study we silenced the CHS genes of apple (Malus × domestica Borkh.) and observed a loss of pigmentation in the fruit skin, flowers and stems. More surprisingly, highly silenced lines were significantly reduced in size, with small leaves and shortened internode lengths. Chemical analysis also revealed that the transgenic shoots contained greatly reduced concentrations of flavonoids which are known to modulate auxin flow. An auxin transport study verified this, with an increased auxin transport in the CHS-silenced lines. Overall, these findings suggest that auxin transport in apple has adapted to take place in the presence of high endogenous concentrations of flavonoids. Removal of these compounds therefore results in abnormal auxin movement and a highly disrupted growth pattern. © 2013 Landes Bioscience.

Freedom to choose? Embryo selection, reproductive decision-making and the role of the state

Involving the biopsy of an eight-cell embryo, PGD has been hailed as a means of making reproductive decisions without having to face the heart-wrenching decision to abort an affected foetus. However, controversy around the kinds of traits for which testing can be done, and who has access to the technology, has led to questions about the way in which the technology is developing. Women who are allowed to access in vitro fertilisation (IVF) services can currently also access PGD in limited circumstances.

Reproductive technology, public policy and single motherhood

In mid 2000, the Australian community engaged in a national debate over access to infertility treatment services. The debate was sparked by a Federal Court decision in late July. That decision, by Justice Sundberg in the case of McBain v State of Victoria 1 held that the provisions of the Infertility Treatment Act 1995 (Vic) which limited eligibility for infertility treatment to women who were married or in heterosexual de facto relationships, were inconsistent with section 22 of the Commonwealth Sex Discrimination Act 1984 (Cth) which prohibits discrimination on the basis of marital status. Justice Sundberg held that, by virtue of section 109 of the Constitution, 2 the provisions of the Victorian Act were inoperative to the extent of the inconsistency between the State and Commonwealth legislation.

Genetic technologies and the regulation of reproductive decision-making in Australia

This article provides a critical analysis of the current Australian regulatory landscape at the interface between genetics and reproductive decision- making. The authors argue that a comparative analysis with other countries and international law and a contextual examination of the way law regulates concepts such as disease and health, abnormality and normality is necessary before we can develop appropriate policy and legislative responses in this area. Specific genetic testing technologies are considered including prenatal genetic testing, preimplantation genetic diagnosis and inheritable genetic modification. An increasing number of members of the Australian community are using genetic testing technologies when they decide to have a baby. The authors argue that as concepts of disease and health vary among members of the community and the potential to test for traits other than illness increases, a new tension arises between an ethic of individual choice and a role for government in regulating reproductive decision-making.