Editorial: The Mammary Stroma in Normal Development and Function

The mammary gland can no longer be simply viewed as an organ composed of epithelial cells within a passive stromal microenvironment. Many lines of evidence have evolved to reinforce the notion that mammary epithelial cell growth, differentiation, lactation and progression to cancer involves bidirectional interactions between the epithelial population and its surrounding stroma. Within this stroma are numerous systems that are all capable of modulating epithelial function. In this context, the mammary stroma is not simply a depot of adipose tissue in which mammary epithelial cells undertake a unique growth and differentiation process, although adipocytes can impart numerous modulatory signals to epithelial cells, and vice versa. Rather, the stromal environment constitutes and supports a critical vasculature that supplies nutrients and endocrine cues, a lymphatic system that not only removes metabolites but also provides an intimate interface with the immune system, and an extracellular matrix scaffold in which epithelial cells grow, differentiate and regress. Ultimately all of these components play a critical role in directing the epithelial phenotype during normal mammary gland growth and function. An increasing appreciation for these different systems demands a view of mammary epithelial cells in a much different light, and further necessitates the development of model systems that incorporate and integrate increasing complexity

Uterine selection of human embryos at implantation

Human embryos frequently harbor large-scale complex chromosomal errors that impede normal development. Affected embryos may fail to implant although many first breach the endometrial epithelium and embed in the decidualizing stroma before being rejected via mechanisms that are poorly understood. Here we show that developmentally impaired human embryos elicit an endoplasmic stress response in human decidual cells. A stress response was also evident upon in vivo exposure of mouse uteri to culture medium conditioned by low-quality human embryos. By contrast, signals emanating from developmentally competent embryos activated a focused gene network enriched in metabolic enzymes and implantation factors. We further show that trypsin, a serine protease released by pre-implantation embryos, elicits Ca2+ signaling in endometrial epithelial cells. Competent human embryos triggered short-lived oscillatory Ca2+ fluxes whereas low-quality embryos caused a heightened and prolonged Ca2+ response. Thus, distinct positive and negative mechanisms contribute to active selection of human embryos at implantation

Predictors of HIV and Syphilis among Men Who Have Sex with Men in a Chinese Metropolitan City: Comparison of Risks among Students and Non-Students

Men who have sex with men (MSM) are at a substantial risk of HIV, given rising HIV prevalence in urban China. Adolescent and adult students often take HIV-related risk as part of sexual exploration. We compared the risks of HIV and syphilis infections and risky sexual behaviors between student and non-student among urban MSM.Respondent driven sampling approach was used to recruit men who were self-identified as MSM in Chongqing Metropolitan City in southwestern China in 2009. Each participant completed a computer-assisted self-interview which collected demographic and behavioral data, and provided blood specimens for HIV and syphilis testing. Multivariable logistic regression analyses identified predictors for HIV and syphilis infections while comparing student and non-student MSM.Among 503 MSM participants, 36.4% were students, of whom 84.2% were in college. The adjusted prevalence of HIV infection was 5.5% (95% confidence interval [CI]: 2.1%-10.2%) in students and 20.9% (95% CI: 13.7%-27.5%) in non-students; the adjusted prevalence of syphilis was 4.4% (95% CI: 0.7%-9.0%) in students and 7.9% (95% CI: 3.6%-12.9%) in non-students (P = 0.12). Two groups had similar risky sexual behaviors such as number of sexual partners and exchanging sex for money. Multivariate analysis showed that students had lower HIV prevalence than non-students (adjusted odds ratio [AOR]: 0.3; 95% CI: 0.1-0.8) adjusting for age, ethnicity and other variables.Student MSM have lower HIV and similar syphilis prevalence compared with non-student MSM. However, due to a shorter duration of sexual experience and high prevalence of at-risk sexual behaviors among student MSM, HIV risk might be quite high in students as in non-students

A novel class of microRNA-recognition elements that function only within open reading frames.

MicroRNAs (miRNAs) are well known to target 3' untranslated regions (3' UTRs) in mRNAs, thereby silencing gene expression at the post-transcriptional level. Multiple reports have also indicated the ability of miRNAs to target protein-coding sequences (CDS); however, miRNAs have been generally believed to function through similar mechanisms regardless of the locations of their sites of action. Here, we report a class of miRNA-recognition elements (MREs) that function exclusively in CDS regions. Through functional and mechanistic characterization of these 'unusual' MREs, we demonstrate that CDS-targeted miRNAs require extensive base-pairing at the 3' side rather than the 5' seed; cause gene silencing in an Argonaute-dependent but GW182-independent manner; and repress translation by inducing transient ribosome stalling instead of mRNA destabilization. These findings reveal distinct mechanisms and functional consequences of miRNAs that target CDS versus the 3' UTR and suggest that CDS-targeted miRNAs may use a translational quality-control-related mechanism to regulate translation in mammalian cells

Genomic analysis of Pseudomonas putida: genes in a genome island are crucial for nicotine degradation

Nicotine is an important chemical compound in nature that has been regarded as an environmental toxicant causing various preventable diseases. Several bacterial species are adapted to decompose this heterocyclic compound, including Pseudomonas and Arthrobacter. Pseudomonas putida S16 is a bacterium that degrades nicotine through the pyrrolidine pathway, similar to that present in animals. The corresponding late steps of the nicotine degradation pathway in P. putida S16 was first proposed and demonstrated to be from 2,5-dihydroxy-pyridine through the intermediates N-formylmaleamic acid, maleamic acid, maleic acid, and fumaric acid. Genomics of strain S16 revealed that genes located in the largest genome island play a major role in nicotine degradation and may originate from other strains, as suggested by the constructed phylogenetic tree and the results of comparative genomic analysis. The deletion of gene hpo showed that this gene is essential for nicotine degradation. This study defines the mechanism of nicotine degradation

Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes.

A considerable body of research indicates that mammary gland branching morphogenesis is dependent, in part, on the extracellular matrix (ECM), ECM-receptors, such as integrins and other ECM receptors, and ECM-degrading enzymes, including matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). There is some evidence that these ECM cues affect one or more of the following processes: cell survival, polarity, proliferation, differentiation, adhesion, and migration. Both three-dimensional culture models and genetic manipulations of the mouse mammary gland have been used to study the signaling pathways that affect these processes. However, the precise mechanisms of ECM-directed mammary morphogenesis are not well understood. Mammary morphogenesis involves epithelial 'invasion' of adipose tissue, a process akin to invasion by breast cancer cells, although the former is a highly regulated developmental process. How these morphogenic pathways are integrated in the normal gland and how they become dysregulated and subverted in the progression of breast cancer also remain largely unanswered questions

Factors Influencing Chinese Male's Willingness to Undergo Circumcision: A Cross-Sectional Study in Western China

BACKGROUND: Male circumcision (MC) has been shown to reduce the risk of female to male transmission of HIV. The goal of this survey was to explore the acceptability of MC among the Chinese and to identify factors associated with circumcision preference. METHODS: A cross-sectional survey was conducted between September 2009 and December 2010. We interviewed 2,219 male community participants, from three high HIV prevalence provinces in western China. A structured questionnaire was used to collect data on MC knowledge, willingness to accept MC, reasons to accept or refuse MC, and sexual behaviors and health. For those who refused MC, a health education intervention providing information on the benefits of circumcision was conducted. We used multiple logistic regression models to identify factors associated with the acceptability of MC. RESULTS: Of the respondents (n = 2,219), 44.6% (989/2,219) reported they would accept MC for the following reasons: promotion of female partners' hygiene (60.3%), redundant foreskin (59.4%), prevention of penile cancer (50.2%), enhanced sexual pleasure (41.4%), and protection against HIV and STDs (34.2%). The multivariable logistic regression showed that five factors were associated with MC willingness: long foreskin (OR = 15.98), residing in Xinjiang province (OR = 3.69), being younger than 25 (OR = 1.60), knowing hazards of redundant foreskin (OR = 1.78), and having a friend who underwent circumcision (OR = 1.36). CONCLUSION: The acceptability of male circumcision was high among the general population in China. Our study elucidates the factors associated with circumcision preference and suggests that more health education campaigns about positive health effects are necessary to increase the MC rate in China

Systematic identification of functional modules and cis-regulatory elements in Arabidopsis thaliana

<p>Abstract</p> <p>Background</p> <p>Several large-scale gene co-expression networks have been constructed successfully for predicting gene functional modules and cis-regulatory elements in Arabidopsis (<it>Arabidopsis thaliana</it>)<it>.</it> However, these networks are usually constructed and analyzed in an <it>ad hoc</it> manner. In this study, we propose a completely parameter-free and systematic method for constructing gene co-expression networks and predicting functional modules as well as cis-regulatory elements.</p> <p>Results</p> <p>Our novel method consists of an automated network construction algorithm, a parameter-free procedure to predict functional modules, and a strategy for finding known cis-regulatory elements that is suitable for consensus scanning without prior knowledge of the allowed extent of degeneracy of the motif. We apply the method to study a large collection of gene expression microarray data in Arabidopsis. We estimate that our co-expression network has ~94% of accuracy, and has topological properties similar to other biological networks, such as being scale-free and having a high clustering coefficient. Remarkably, among the ~300 predicted modules whose sizes are at least 20, 88% have at least one significantly enriched functions, including a few extremely significant ones (ribosome, <it>p</it> < 1E-300, photosynthetic membrane, <it>p</it> < 1.3E-137, proteasome complex, <it>p</it> < 5.9E-126). In addition, we are able to predict cis-regulatory elements for 66.7% of the modules, and the association between the enriched cis-regulatory elements and the enriched functional terms can often be confirmed by the literature. Overall, our results are much more significant than those reported by several previous studies on similar data sets. Finally, we utilize the co-expression network to dissect the promoters of 19 Arabidopsis genes involved in the metabolism and signaling of the important plant hormone gibberellin, and achieved promising results that reveal interesting insight into the biosynthesis and signaling of gibberellin.</p> <p>Conclusions</p> <p>The results show that our method is highly effective in finding functional modules from real microarray data. Our application on Arabidopsis leads to the discovery of the largest number of annotated Arabidopsis functional modules in the literature. Given the high statistical significance of functional enrichment and the agreement between cis-regulatory and functional annotations, we believe our Arabidopsis gene modules can be used to predict the functions of unknown genes in Arabidopsis, and to understand the regulatory mechanisms of many genes.</p