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Background: MicroRNAs are a population of short non-coding RNAs with widespread negative regulatory impact on mRNA translation. Unrestricted somatic stem cells (USSC) are a rare population in human cord blood that can be induced into cells representative of all three germinal layers. Here we analyzed the functional impact of miRNAs on the osteogenic differentiation in USSC. Results: Gene expression profiling identified 20 microRNAs that were consistently upregulated during osteogenic differentiation of two different USSC cell lines (SA5/73 and SA8/25). Bioinformatic target gene prediction indicated that among these microRNAs, miR-10a, -22, -26a, -26b, and -29b recognize transcripts that encode a set of proteins inhibiting osteogenesis. We subsequently verified osteo-inhibitory CDK6, CTNNBIP1, HDAC4, and TOB1 and osteopromoting SMAD1 as targets of these microRNAs. In Western blot analyses demonstrated that endogenous levels of CDK6 and HDAC4 were downregulated during osteogenic differentiation of USSC and reduced following ectopic expression of miR-26a/b and miR-29b. In contrast, endogenous expression of SMAD1, targeted by miR-26a/b, was unaltered during osteogenic differentiation of USSC or following ectopic expression of miR-26a/b. Functional overexpression analyses using microRNA mimics revealed that miR-26a/b, as well as miR-29b strongly accelerated osteogenic differentiation of USSC as assessed by Alizarin-Red staining and calcium-release assays. Conclusions: miR-26a/b and miR-29b are upregulated during osteogenic differentiation of USSC and share target genes inhibiting osteogenesis. Furthermore, these microRNAs accelerate osteogenic differentiation, likely mediated by osteo-inhibitory proteins such as CDK6 and HDAC4. [ABSTRACT FROM AUTHOR]

Sexual and nonsexual modes of transmission of human herpesvirus 8 (HHV8) have been suggested, but specific routes remian unclear. Therefore, the objective of this study was to assess risk factors for HHV8 seropositivty and determine specific sexual practice associated with HHV8 seroconversion. Sera from 1, 458 homosexual men (Amsterdam Cohort Study, 1984–1996) were tested for antibodies to HHV8 with a modified version of an enzyme immunoassay, using recombinant HHV8 lytic phase capsid (ORF65) and latent phase nuclear (ORF73) proteins. HHV8 seroprevalence at study entry was 20.9% (305/1, 458); was highest among those with positive human immunodeficiency virus (HIV) status, no steady partner, and southern European or Latin American nationality; and increased with older age and higher number of sexual partners. During followup, 215 men seroconverted for HHV8 (incidence: 3.6/100 person-years). Both prevalence and incidence rates remained more or less table during the study period. Orogenital insertive sex (odds ration (OR) = 5.95; 95% confidence interval (CI): 2.88, 12.29) or orogential receptive sex (OR = 4.29; 95% CI: 2.11, 8.71) with more than five partners in the past 6 months, older age (OR = 2.89; 95% CI: 1.13, 7.34, when oldern than 45 years), and preceding HIV infection (OR = 2.47; 95% CI: 1.53, 3.99) were independent predictors for HHVB seroconversion. The authors found strong evidence for orogenital transmission of HHV8 among homosexual men. Am J Epidemiol 2000; 151: 21324. [ABSTRACT FROM PUBLISHER]

There has been a recent rise in optimism about Africa's prospects: increased economic growth; renewed regional and national political commitments to good governance; and fewer conflicts. Yet, given current trends and with less than eight years until 2015, Africa is likely to fail to meet every single one of the Millennium Development Goals (MDGs). Home to almost one-third of the world's poor, Africa's challenges remain as daunting as ever. Despite highly publicized increased growth in some economies, the combined economies of Africa have, on average, actually shrunk and are far from meeting the required 7 per cent growth needed to tackle extreme poverty. A similar picture emerges from the analysis of Africa's performance on the other MDGs. In a world where security and development are inextricably connected in complex and multifaceted ways, Africans are, as a result, among the most insecure. By reviewing a select number of political, security and socio-economic indicators for the continent, this analysis evaluates the reasons underlying Africa's continuing predicament. It identifies four critical issues: ensuring peace and security; fostering good governance; fighting HIV/ AIDS; and managing the debt crisis. In assessing these developmental security challenges, the article recalls that the MDGs are more than time bound, quantified targets for poverty alleviation–they also represent a commitment by all members of the international community, underwritten by principles of co-responsibility and partnership, to an enlarged notion of development based on the recognition that human development is key to sustaining social and economic progress. In recent years, and often following failures, especially in Africa, to protect civilian populations from the violence and predation of civil wars, a series of high-level commissions and expert groups have conducted strategic reviews of the UN system and its function in global politics. The debate has also developed at the theoretical level involving both a recon-ceptualization of security, from state centred norms to what is referred to as the globalization of security around the human security norm. There has also been a reconceptualization of peacekeeping, where the peacekeeping force has enough robustness to use force not only to protect populations under the emergent responsibility to protect norm, but also enough conflict resolution capacity to facilitate operations across the conflict–development–peacebuilding continuum. This article opens up a discussion of how these ideas might be relevant to security regime building and conflict resolution in African contexts, and suggests how initiatives in Africa might begin to make a contribution to the theory and practice of cosmopolitan peacekeeping. [ABSTRACT FROM AUTHOR]

HIV/AIDS is fundamentally an issue of human rights. To the right to medical provision must be added rights to the provisions of social justice necessary to the prevention and alleviation of HIV/AIDS. China has become the focus of international concern over HIV/AIDS. Applying the concepts of 'capabilities poverty', 'discursive democracy', gender construction, 'structural violence' and the 'hypermasculine state', the study identifies the threat to China's women from HIV/AIDS; evaluates the factors contributing to this threat with reference to issues of human rights; and assesses the quality of the national and international response to the HIV/AIDS threat. It is argued that there is a growing threat to women from HIV infection in China; that there are gender-specific factors that render women in China especially vulnerable; that the belated epidemiological response is weak and its capability to meet the threat seriously weakened by social patriarchy; and that, ultimately, the HIV/AIDS threat to China's women is an issue that can only be resolved through political reform leading to discursive democracy and social justice. [ABSTRACT FROM AUTHOR]

Presents information on a study which investigated the relationship between seroconversion to lytic-phase capside and latent-phase nuclear antigens and human herpesvirus 8 (HHV8) infection. HHV8 antibody profiles in the seroconverter population; Materials and methods of the study; Results and discussion.

Lung neuroendocrine tumours (NETs) are a heterogeneous group of neoplasms that includes typical carcinoids (TC), atypical carcinoids (AC), small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinomas (LCNEC) (WHO 2004 Classification). The histopathlogical differentiation between these entities is sometimes challenging. To help provide a better molecular diagnostic and prognostic tool we identified in this study miRNA biomarkers that are differentially expressed in these four pathological types. RNA samples were extracted and validated from formalinfixed paraffin-embedded (FFPE) tissue blocks. Using our newly developed approach; barcoded small RNA sequencing we generated miRNA expression profiles for a test set of three TCs, nine ACs, four LCNECs, and five SCLCs through. Our results were further confirmed by realtime PCR. Unsupervised hierarchical clustering indicated a clear separation of all NET groups from each other. Through feature selection, we identified candidate miRNA and cistronic miRNA clusters that separate TC vs. AC; LCNEC vs. SCLC, and carcinoid vs. neuroendocrine carcinomas. Our preliminary data revealed that a large miRNA cluster on chromosome 14q32 was downregulated in carcinomas (SCLC, LCNEC) vs. carcinoids (TC, AC). In this study we report different miRNA biomarkers with potential diagnostic and prognostic value for lung NETs. [ABSTRACT FROM AUTHOR]

A response by Thomas Briese et al to a letter to the editor about their article on the prior evidence of putative novel rhinovirus species in Australia is presented.

Background: Accurate cancer classification is essential for correct treatment selection and better prognostication. microRNAs (miRNAs) are small RNA molecules that negatively regulate gene expression, and their dyresgulation is a common disease mechanism in many cancers. Through a clearer understanding of miRNA dysregulation in cancer, improved mechanistic knowledge and better treatments can be sought. Results: We present a topology-preserving deep learning framework to study miRNA dysregulation in cancer. Our study comprises miRNA expression profiles from 3685 cancer and non-cancer tissue samples and hierarchical annotations on organ and neoplasticity status. Using unsupervised learning, a two-dimensional topological map is trained to cluster similar tissue samples. Labelled samples are used after training to identify clustering accuracy in terms of tissue-of-origin and neoplasticity status. In addition, an approach using activation gradients is developed to determine the attention of the networks to miRNAs that drive the clustering. Using this deep learning framework, we classify the neoplasticity status of held-out test samples with an accuracy of 91.07%, the tissue-of-origin with 86.36%, and combined neoplasticity status and tissue-of-origin with an accuracy of 84.28%. The topological maps display the ability of miRNAs to recognize tissue types and neoplasticity status. Importantly, when our approach identifies samples that do not cluster well with their respective classes, activation gradients provide further insight in cancer subtypes or grades. Conclusions: An unsupervised deep learning approach is developed for cancer classification and interpretation. This work provides an intuitive approach for understanding molecular properties of cancer and has significant potential for cancer classification and treatment selection. [ABSTRACT FROM AUTHOR]