Extensive Copy-Number Variation of Young Genes across Stickleback Populations

MM received funding from the Max Planck innovation funds for this project. PGDF was supported by a Marie Curie European Reintegration Grant (proposal nr 270891). CE was supported by German Science Foundation grants (DFG, EI 841/4-1 and EI 841/6-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The Methyl-CpG Binding Proteins Mecp2, Mbd2 and Kaiso Are Dispensable for Mouse Embryogenesis, but Play a Redundant Function in Neural Differentiation

The precise molecular changes that occur when a neural stem (NS) cell switches from a programme of self-renewal to commit towards a specific lineage are not currently well understood. However it is clear that control of gene expression plays an important role in this process. DNA methylation, a mark of transcriptionally silent chromatin, has similarly been shown to play important roles in neural cell fate commitment in vivo. While DNA methylation is known to play important roles in neural specification during embryonic development, no such role has been shown for any of the methyl-CpG binding proteins (Mecps) in mice.. No evidence for functional redundancy between these genes in embryonic development or in the derivation or maintenance of neural stem cells in culture was detectable. However evidence for a defect in neuronal commitment of triple knockout NS cells was found.Although DNA methylation is indispensable for mammalian embryonic development, we show that simultaneous deficiency of three methyl-CpG binding proteins genes is compatible with apparently normal mouse embryogenesis. Nevertheless, we provide genetic evidence for redundancy of function between methyl-CpG binding proteins in postnatal mice

Neurodevelopment Genes in Lampreys Reveal Trends for Forebrain Evolution in Craniates

The forebrain is the brain region which has undergone the most dramatic changes through vertebrate evolution. Analyses conducted in lampreys are essential to gain insight into the broad ancestral characteristics of the forebrain at the dawn of vertebrates, and to understand the molecular basis for the diversifications that have taken place in cyclostomes and gnathostomes following their splitting. Here, we report the embryonic expression patterns of 43 lamprey genes, coding for transcription factors or signaling molecules known to be involved in cell proliferation, stemcellness, neurogenesis, patterning and regionalization in the developing forebrain. Systematic expression patterns comparisons with model organisms highlight conservations likely to reflect shared features present in the vertebrate ancestors. They also point to changes in signaling systems –pathways which control the growth and patterning of the neuroepithelium-, which may have been crucial in the evolution of forebrain anatomy at the origin of vertebrates

Direct Recognition of Fusobacterium nucleatum by the NK Cell Natural Cytotoxicity Receptor NKp46 Aggravates Periodontal Disease

Periodontitis is a common human chronic inflammatory disease that results in the destruction of the tooth attachment apparatus and tooth loss. Although infections with periopathogenic bacteria such as Porphyromonas gingivalis (P. gingivalis) and Fusobacterium nucleatum (F. nucleatum) are essential for inducing periodontitis, the nature and magnitude of the disease is determined by the host's immune response. Here, we investigate the role played by the NK killer receptor NKp46 (NCR1 in mice), in the pathogenesis of periodontitis. Using an oral infection periodontitis model we demonstrate that following F. nucleatum infection no alveolar bone loss is observed in mice deficient for NCR1 expression, whereas around 20% bone loss is observed in wild type mice and in mice infected with P. gingivalis. By using subcutaneous chambers inoculated with F. nucleatum we demonstrate that immune cells, including NK cells, rapidly accumulate in the chambers and that this leads to a fast and transient, NCR1-dependant TNF-α secretion. We further show that both the mouse NCR1 and the human NKp46 bind directly to F. nucleatum and we demonstrate that this binding is sensitive to heat, to proteinase K and to pronase treatments. Finally, we show in vitro that the interaction of NK cells with F. nucleatum leads to an NCR1-dependent secretion of TNF-α. Thus, the present study provides the first evidence that NCR1 and NKp46 directly recognize a periodontal pathogen and that this interaction influences the outcome of F. nucleatum-mediated periodontitis

Social machines:A philosophical engineering

In Weaving the Web (2000), Berners-Lee defines Social Machines as biotechnologically hybrid Web-processes on the basis of which, “high-level activities, which have occurred just within one human’s brain, will occur among even larger more interconnected groups of people acting as if the shared a larger intuitive brain” (201–202). The analysis and design of Social Machines has already started attracting considerable attention both within the industry and academia. Web science, however, is still missing a clear definition of what a Social Machine is, which has in turn resulted in several calls for a “philosophical engineering” (Halpin 2013; Hendler & Berners-Lee 2010); Halpin et al. 2010). This paper is a first attempt to respond to this call, by combining contemporary philosophy of mind and cognitive science with epistemology. The idea of philosophical engineering implies that a sufficiently good conception of Social Machines should be of both theoretical and practical advantage. To demonstrate how the present approach can satisfy both objectives it will be used in order to address one of Wikipedia’s (the most famous Social Machine to date) most worrying concerns—i.e., the current and ongoing decline in the number of its active contributors (Halfacker et al. 2012)

Pseudoneoplastic lesions of the testis and paratesticular structures

Pseudotumors or tumor-like proliferations (non-neoplastic masses) and benign mimickers (non-neoplastic cellular proliferations) are rare in the testis and paratesticular structures. Clinically, these lesions (cysts, ectopic tissues, and vascular, inflammatory, or hyperplastic lesions) are of great interest for the reason that, because of the topography, they may be relevant as differential diagnoses. The purpose of this paper is to present an overview of the pseudoneoplasic entities arising in the testis and paratesticular structures; emphasis is placed on how the practicing pathologist may distinguish benign mimickers and pseudotumors from true neoplasia. These lesions can be classified as macroscopic or microscopic mimickers of neoplasia