Background

Metastatic melanoma is a devastating disease with limited therapeutic options. MicroRNAs (miRNAs) are small non coding RNA molecules with important roles in post-transcriptional gene expression regulation, whose aberrant expression has been implicated in cancer.

Results

We show that the expression of miRNAs from a large cluster on human chromosome 14q32 is significantly down-regulated in melanoma cell lines, benign nevi and melanoma samples relative to normal melanocytes. This miRNA cluster resides within a parentally imprinted chromosomal region known to be important in development and differentiation. In some melanoma cell lines, a chromosomal deletion or loss-of-heterozygosity was observed in the cis-acting regulatory region of this cluster. In several cell lines we were able to re-express two maternally-induced genes and several miRNAs from the cluster with a combination of de-methylating agents and histone de-acetylase inhibitors, suggesting that epigenetic modifications take part in their silencing. Stable over-expression of mir-376a and mir-376c, two miRNAs from this cluster that could be re-expressed following epigenetic manipulation, led to modest growth retardation and to a significant decrease in migration in-vitro. Bioinformatic analysis predicted that both miRNAs could potentially target the 3'UTR of IGF1R. Indeed, stable expression of mir-376a and mir-376c in melanoma cells led to a decrease in IGF1R mRNA and protein, and a luciferase reporter assay indicated that the 3'UTR of IGF1R is a target of both mir-376a and mir-376c.

Conclusions

Our work is the first to show that the large miRNA cluster on chromosome 14q32 is silenced in melanoma. Our results suggest that down-regulation of mir-376a and mir-376c may contribute to IGF1R over-expression and to aberrant negative regulation of this signaling pathway in melanoma, thus promoting tumorigenesis and metastasis.

The research blog has become a popular mechanism for the quick discussion of scholarly information. However, unlike peer-reviewed journals, the characteristics of this form of scientific discourse are not well understood, for example in terms of the spread of blogger levels of education, gender and institutional affiliations. In this paper we fill this gap by analyzing a sample of blog posts discussing science via an aggregator called ResearchBlogging.org (RB). ResearchBlogging.org aggregates posts based on peer-reviewed research and allows bloggers to cite their sources in a scholarly manner. We studied the bloggers, blog posts and referenced journals of bloggers who posted at least 20 items. We found that RB bloggers show a preference for papers from high-impact journals and blog mostly about research in the life and behavioral sciences. The most frequently referenced journal sources in the sample were: Science, Nature, PNAS and PLoS One. Most of the bloggers in our sample had active Twitter accounts connected with their blogs, and at least 90% of these accounts connect to at least one other RB-related Twitter account. The average RB blogger in our sample is male, either a graduate student or has been awarded a PhD and blogs under his own name.

Many viruses escape the cellular immune response by downregulating cell surface expression of major histocompatibility complex (MHC) class I molecules. However, infection of cells with flaviviruses can upregulate the expression of these molecules. In this study we analyzed the expression of MHC class I in K562 and THP-1 human cell lines that were stably transfected with self-replicating subgenomic dengue virus RNA (replicons) and express all the dengue virus nonstructural proteins together. We show that MHC class I expression is upregulated in the dengue virus replicon-expressing cells and that the binding of natural killer (NK) inhibitory receptors to these cells is augmented. This upregulation results in reduced susceptibility of the dengue virus replicon-expressing cells to NK lysis, indicating a possible mechanism for evasion of the dengue virus from NK cell recognition. Visualizing MHC class I expression in replicon-containing K562 and THP-1 cells by confocal microscopy demonstrated aggregation of MHC class I molecules on the cell surface. Finally, replicon-expressing K562 cells manifested increased TAP (transporter associated with antigen processing) and LMP (low-molecular-mass protein) gene transcription, while replicon-expressing THP-1 cells manifested increased NF-κB activity and MHC class I transcription. We suggest that expression of dengue virus nonstructural proteins is sufficient to induce MHC class I upregulation through both TAP-dependent and -independent mechanisms. Additionally, aggregation of MHC class I molecules on the cell membrane also contributes to significantly higher binding of low-affinity NK inhibitory receptors, resulting in lower sensitivity to lysis by NK cells.

Background

Lung cancer is the commonest cause of cancer death in developed countries. Adenocarcinoma is becoming the most common form of lung cancer. Cigarette smoking is the main risk factor for lung cancer. Long-term cigarettes smoking may be characterized by genetic alteration and diffuse injury of the airways surface, named field cancerization, while cancer in non-smokers is usually clonally derived. Detecting specific genes expression changes in non-cancerous lung in smokers with adenocarcinoma may give us instrument for predicting smokers who are going to develop this malignancy.

Objectives

We described the gene expression in non-cancerous lungs from 21 smoker patients with lung adenocarcinoma and compare it to gene expression in non-cancerous lung tissue from 10 non-smokers with primary lung adenocarcinoma.

Methods

Total RNA was isolated from peripheral non-cancerous lung tissue. The cDNA was hybridized to the U133A GeneChip array. Hierarchical clustering analysis on genes obtained from smokers and non-smokers, after subtracting were exported to the Ingenuity Pathway Analysis software for further analysis.

Results

The genes subtraction resulted in disclosure of 36 genes with high score. They were subsequently mapped and sorted based on location, cellular components, and biochemical activity. The gene functional analysis disclosed 20 genes, which are involved in cancer process (P = 7.05E-5 to 2.92E-2).

Conclusion

Detected genes may serve as a predictor for smokers who may be at high risk of developing lung cancer. In addition, since these genes originating from non-cancerous lung, which is the major area of the lungs, a sample from an induced sputum may represent it.

Antiviral immune defenses involve natural killer (NK) cells. We previously showed that the NK-activating receptor NKp44 is involved in the functional recognition of H1-type influenza virus strains by NK cells. In the present study, we investigated the interaction of NKp44 and the hemagglutinin of a primary influenza virus H5N1 isolate. Here we show that recombinant NKp44 recognizes H5-expressing cells and specifically interacts with soluble H5 hemagglutinin. H5-pseudotyped lentiviral particles bind to NK cells expressing NKp44. Following interaction with target cells expressing H5, pseudotyped lentiviral particles, or membrane-associated H5, NK cells show NKp44-mediated induced activity. These findings indicate that NKp44-H5 interactions induce functional NK activation.

The natural cytotoxic receptors (NCRs) are a unique set of activating proteins expressed mainly on the surface of natural killer (NK) cells. The NCRs, which include three members; NKp46, NKp44 and NKp30, are critically involved in NK cytotoxicity against different targets, including a wide range of tumor cells derived from various origins. Even though the tumor ligands of the NCRs have not been identified yet, the selective manner by which these receptors target tumor cells may provide an excellent basis for the development of novel anti-tumor therapies. To test the potential use of the NCRs as anti-tumor agents, we generated soluble NCR-Ig fusion proteins in which the constant region of human IgG1 was fused to the extracellular portion of the receptor. We demonstrate, using two different human prostate cancer cell lines, that treatment with NKp30-Ig, dramatically inhibits tumor growth in vivo. Activated macrophages were shown to mediate an ADCC response against the NKp30-Ig coated prostate cell lines. Finally, the Ig fusion proteins were also demonstrated to discriminate between benign prostate hyperplasia and prostate cancer. This may provide a novel diagnostic modality in the difficult task of differentiating between these highly common pathological conditions.

The wide dissemination and expanding applications of functional MRI have not escaped the attention of the media or discussion in the wider public arena. From the bench to the bedside, this technology has introduced substantial ethical challenges. Are the boundaries of what it can and cannot achieve being communicated to the public? Are its limitations understood? And given the complexities that are inherent to neuroscience, are current avenues for communication adequate?

Advances in neuroscience are increasingly intersecting with issues of ethical, legal, and social interest. This study is an analysis of press coverage of an advanced technology for brain imaging, functional magnetic resonance imaging, that has gained significant public visibility over the past ten years. Discussion of issues of scientific validity and interpretation dominated over ethical content in both the popular and specialized press. Coverage of research on higher order cognitive phenomena specifically attributed broad personal and societal meaning to neuroimages. The authors conclude that neuroscience provides an ideal model for exploring science communication and ethics in a multicultural context.

Background

While it is known that the majority of pages on the World Wide Web are in English, little is known about the preferred language of users searching for health information online.

Objectives

(1) To help global and domestic publishers, for example health and food agencies, to determine the need for translation of online information from English into local languages. (2) To help these agencies determine which language(s) they should select when publishing information online in target nations and for target subpopulations within nations.

Methods

To estimate the percentage of Web publishers that translate their health and food websites, we measured the frequency at which domain names retrieved by Google overlap for language translations of the same health-related search term. To quantify language choice of searchers from different countries, Google provided estimates of the rate at which its search engine was queried in six languages relative to English for the terms “avian flu,” “tuberculosis,” “schizophrenia,” and “maize” (corn) from January 2004 to April 2006. The estimate was based on a 20% sample of all Google queries from 227 nations.

Results

We estimate that 80%-90% of health- and food-related institutions do not translate their websites into multiple languages, even when the information concerns pandemic disease such as avian influenza. Although Internet users are often well-educated, there was a strong preference for searching for health and food information in the local language, rather than English. For “avian flu,” we found that only 1% of searches in non-English-speaking nations were in English, whereas for “tuberculosis” or “schizophrenia,” about 4%-40% of searches in non-English countries employed English. A subset of searches for health information presumably originating from immigrants occurred in their native tongue, not the language of the adopted country. However, Spanish-language online searches for “avian flu,” “schizophrenia,” and “maize/corn” in the United States occurred at only <1% of the English search rate, although the US online Hispanic population constitutes 12% of the total US online population. Sub-Saharan Africa and Bangladesh searches for health information occurred in unexpected languages, perhaps reflecting the presence of aid workers and the global migration of Internet users, respectively. In Latin America, indigenous-language search terms were often used rather than Spanish.

Conclusions

(1) Based on the strong preference for searching the Internet for health information in the local language, indigenous language, or immigrant language of origin, global and domestic health and food agencies should continue their efforts to translate their institutional websites into more languages. (2) We have provided linguistic online search pattern data to help health and food agencies better select languages for targeted website publishing.