Oestrogen-modulated gene expression in the human endometrium

To identify key regulatory mechanisms in the growth and development of the human endometrium, microarray analysis was performed on uncultured human endometrium collected during menstruation (M) and the late-proliferative (LATE-P)-phase of the menstrual cycle, as well as after 24 h incubation in the presence of oestradiol (17beta-E2). We demonstrate the expression of novel gene transcripts in the human endometrium. i.e. mucin-9, novel oestrogen-responsive gene transcripts, i.e. gelsolin and flotillin-1, and genes known to be expressed in human endometrium but not yet shown to be oestrogen responsive, i.e. connexin-37 and TFF1/pS2. Genes reported to be expressed during the implantation window and implicated in progesterone action, i.e. secretoglobin family 2A, member 2 (mammaglobin) and homeobox-containing proteins, were up-regulated in uncultured LATE-P-phase endometrium compared to M-phase endometrium. Some gene transcripts are regulated directly by 17beta-E2 alone, others are influenced by the in vivo environment as well. These observations emphasise that the regulation of endometrium maturation by oestrogen entails more then just stimulation of cell proliferation.

Estrogen and the endometrium: lessons learned from gene expression profiling in rodents and human

To date, research into the biological processes and molecular mechanisms associated with endometrial receptivity and embryo implantation has been a focus of attention, whereas the complex events that occur in the human endometrium during the menstrual and proliferative phase under the influence of estrogen have received little attention. The objective of this review is to provide an update of our current understanding of the actions of estrogen on both human and rodent endometrium, with special emphasis on the regulation of uterine growth and cell proliferation, and the value of global gene expression analysis, in increasing understanding of these processes.

Observing the mother-infant feeding interaction

Early parenting is critical to effective attachment and a range of positive developmental outcomes for children. Feeding is a key task of early parenting and increasing evidence indicates that early feeding practices are important for the development of self-regulation of intake and food preferences which in turn are predictors of later obesity risk. However, relatively little is known about the mother-infant interaction at the transition to solids among typically developing children. This study aimed to describe parenting strategies used by mothers at the transition from milk feeding to solid food. Twenty mother-infant dyads were video-taped during a feeding interaction and data was analysed to describe maternal use of parenting strategies. It was predicted that positive feeding strategies would be correlated with lower levels of Infant Food Refusal (IFR), higher maternal sensitivity, and better overall parenting scores. The opposite was predicted for negative feeding strategies. It was found that positive strategy use and general parenting scores were significantly correlated in the predicted direction, however maternal instruction, aversive contact and ineffective strategy use were significantly correlated with and predictive of IFR. Additionally, it was hypothesised that maternal strategy use would deteriorate towards the end of the interaction, and this hypothesis was partially supported: significantly more negative strategy use was observed in the last third of the interaction, whilst positive strategy use remained consistent through the feeding interaction. The findings have important implications for early feeding parent education and intervention programs.

Tumor-suppressor gene promoter hypermethylation in saliva of head and neck cancer patients

Head and neck squamous cell carcinoma (HNSCC) accounts for a bulk of the oral and laryngeal cancers, the majority (70%) of which are associated with smoking and excessive drinking, major known risk factors for the development of HNSCC. In contrast to reports that suggest an inverse relationship between smoking and global DNA CpG methylation, hypermethylation of promoters of a number of genes was detected in saliva collected from patients with HNSCC. Using a sensitive methylation-specific polymerase chain reaction (MSP) assay to determine specific methylation events in the promoters of RASSF1A, DAPK1, and p16 genes, we demonstrate that we can detect tumor presence with an overall accuracy of 81% in the DNA isolated from saliva of patients with HNSCC (n = 143) when compared with the DNA isolated from the saliva of healthy nonsmoker controls (n = 31). The specificity for this MSP panel was 87% and the sensitivity was 80%(with a Fisher exact test P < .0001). In addition, the test panel performed extremely well in the detection of the early stages of HNSCCs, with a sensitivity of 94% and a specificity of 87%, and a high. concordance value of 0.8, indicating an excellent overall agreement between the presence of HNSCC and a positive MSP panel result. In conclusion, we demonstrate that the promoter methylation of RASSF1A, DAPK1, and p16 MSP panel is useful in detecting hypermethylation events in a noninvasive manner in patients with HNSCC.

DNA methylation at the novel CpG sites in the promoter of MED15/PCQAP gene as a biomarker for head and neck cancers

Head and neck cancers (HNCs) represent a significant and ever-growing burden to the modern society, mainly due to the lack of early diagnostic methods. A significant number of HNCs is often associated with drinking, smoking, chewing beetle nut, and human papilloma virus (HPV) infections. We have analyzed DNA methylation patterns in tumor and normal tissue samples collected from head and neck squamous cell carcinoma (HNSCC) patients who were smokers. We have identified novel methylation sites in the promoter of the mediator complex subunit 15 (MED15/PCQAP) gene (encoing a co-factor important for regulation of transcription initiation for promoters of many genes), hypermethylated specifically in tumor cells. Two clusters of CpG dinucleotides methylated in tumors, but not in normal tissue from the same patients, were identified. These CpG methylation events in saliva samples were further validated in a separate cohort of HNSCC patients (who developed cancer due to smoking or HPV infections) and healthy controls using methylation-specific PCR (MSP). We used saliva as a biological medium because of its non-invasive nature, close proximity to the tumors, easiness and it is an economically viable option for large-scale screening studies. The methylation levels for the two identified CpG clusters were significantly different between the saliva samples collected from healthy controls and HNSCC individuals (Welch's t-test returning P, 0.05 and Mann-Whitney test P, 0.01 for both). The developed MSP assays also provided a good discriminative ability with AUC values of 0.70 (P, 0.01) and 0.63 (P, 0.05). The identified novel CpG methylation sites may serve as potential non-invasive biomarkers for detecting HNSCC. © the authors.

Spatially varying ground motion effects on seismic response of adjacent structures considering soil-structure interaction

Spatial variation of seismic ground motions is caused by incoherence effect, wave passage, and local site conditions. This study focuses on the effects of spatial variation of earthquake ground motion on the responses of adjacent reinforced concrete (RC) frame structures. The adjacent buildings are modeled considering soil-structure interaction (SSI) so that the buildings can be interacted with each other under uniform and non-uniform ground motions. Three different site classes are used to model the soil layers of SSI system. Based on fast Fourier transformation (FFT), spatially correlated non-uniform ground motions are generated compatible with known power spectrum density function (PSDF) at different locations. Numerical analyses are carried out to investigate the displacement responses and the absolute maximum base shear forces of adjacent structures subjected to spatially varying ground motions. The results are presented in terms of related parameters affecting the structural response using three different types of soil site classes. The responses of adjacent structures have changed remarkably due to spatial variation of ground motions. The effect can be significant on rock site rather than clay site.

Transcriptome analyses of amoebic gill disease-affected atlantic salmon (Salmo salar) tissues reveal localized host gene suppression

The transcriptome response of Atlantic salmon (Salmo salar) displaying advanced stages of amoebic gill disease (AGD) was investigated. Naïve smolt were challenged with AGD for 19 days, at which time all fish were euthanized and their severity of infection quantified through histopathological scoring. Gene expression profiles were compared between heavily infected and naïve individuals using a 17 K Atlantic salmon cDNA microarray with real-time quantitative RT-PCR (qPCR) verification. Expression profiles were examined in the gill, anterior kidney, and liver. Twenty-seven transcripts were significantly differentially expressed within the gill; 20 of these transcripts were down-regulated in the AGD-affected individuals compared with naïve individuals. In contrast, only nine transcripts were significantly differentially expressed within the anterior kidney and five within the liver. Again the majority of these transcripts were down-regulated within the diseased individuals. A down-regulation of transcripts involved in apoptosis (procathepsin L, cathepsin H precursor, and cystatin B) was observed in AGD-affected Atlantic salmon. Four transcripts encoding genes with antioxidant properties also were down-regulated in AGD-affected gill tissue according to qPCR analysis. The most up-regulated transcript within the gill was an unknown expressed sequence tag (EST) whose expression was 218-fold (± SE 66) higher within the AGD affected gill tissue. Our results suggest that Atlantic salmon experiencing advanced stages of AGD demonstrate general down-regulation of gene expression, which is most pronounced within the gill. We propose that this general gene suppression is parasite-mediated, thus allowing the parasite to withstand or ameliorate the host response. © 2008 Springer Science+Business Media, LLC.

Soil–pile interaction of pile embedded in deep-layered marine sediment under seismic excitation

This paper investigates the soil–pile interaction of a pile embedded in a deep multi-layered soil under seismic excitation considering both kinematic and inertial interaction effects. A comprehensive three-dimensional finite element model is developed and validated using existing results in the literature. The response of the pile in the deep multi-layered soil profile is investigated with respect to pile head response, deflection modes and maximum deflections along the pile. Results show that the pile exhibits complex deflection patterns and that the pile response is influenced by the properties of both the soil profile and the seismic excitation. It is also evident that kinematic interaction effects have a greater influence on the pile response than the inertial interaction effects.

A Likelihood-Maximizing Framework for Enhanced In-Car Speech Recognition Based on Speech Dialog System Interaction

Speech recognition in car environments has been identified as a valuable means for reducing driver distraction when operating noncritical in-car systems. Under such conditions, however, speech recognition accuracy degrades significantly, and techniques such as speech enhancement are required to improve these accuracies. Likelihood-maximizing (LIMA) frameworks optimize speech enhancement algorithms based on recognized state sequences rather than traditional signal-level criteria such as maximizing signal-to-noise ratio. LIMA frameworks typically require calibration utterances to generate optimized enhancement parameters that are used for all subsequent utterances. Under such a scheme, suboptimal recognition performance occurs in noise conditions that are significantly different from that present during the calibration session – a serious problem in rapidly changing noise environments out on the open road. In this chapter, we propose a dialog-based design that allows regular optimization iterations in order to track the ever-changing noise conditions. Experiments using Mel-filterbank noise subtraction (MFNS) are performed to determine the optimization requirements for vehicular environments and show that minimal optimization is required to improve speech recognition, avoid over-optimization, and ultimately assist with semireal-time operation. It is also shown that the proposed design is able to provide improved recognition performance over frameworks incorporating a calibration session only.

Interaction of erythrocyte eicosapentaenoic acid and physical activity predicts reduced risk of mild cognitive impairment

Objectives To evaluate relationships between self-reported physical activity, proportions of long-chain omega-3 polyunsaturated fatty acids (LCn3) in erythrocyte content (percentage of total fatty acids) and risk of mild cognitive impairment (MCI) in older adults. Method A cross-sectional study was conducted. Community-dwelling male and female (n = 84) participants over the age of 65 years with and without MCI were tested for erythrocyte proportions of the LCn3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Physical activity was measured using a validated questionnaire. Results The interaction between erythrocyte EPA, but not DHA, and increased physical activity was associated with increased odds of a non-MCI classification. Conclusion An interaction between physical activity and erythrocyte EPA content (percentage of fatty acids) significantly predicted MCI status in older adults. Randomised control trials are needed to examine the potential for supplementation with EPA in combination with increased physical activity to mitigate the risk of MCI in ageing adults.

Natural mapping and intuitive interaction in videogames

Videogame control interfaces continue to evolve beyond their traditional roots, with devices encouraging more natural forms of interaction growing in number and pervasiveness. Yet little is known about their true potential for intuitive use. This paper proposes methods to leverage existing intuitive interaction theory for games research, specifically by examining different types of naturally mapped control interfaces for videogames using new measures for previous player experience. Three commercial control devices for a racing game were categorised using an existing typology, according to how the interface maps physical control inputs with the virtual gameplay actions. The devices were then used in a within-groups (n=64) experimental design aimed at measuring differences in intuitive use outcomes. Results from mixed design ANOVA are discussed, along with implications for the field.