The proneural wave in the Drosophila optic lobe is driven by an excitable reaction-diffusion mechanism.

In living organisms, self-organised waves of signalling activity propagate spatiotemporal information within tissues. During the development of the largest component of the visual processing centre of the Drosophila brain, a travelling wave of proneural gene expression initiates neurogenesis in the larval optic lobe primordium and drives the sequential transition of neuroepithelial cells into neuroblasts. Here, we propose that this 'proneural wave' is driven by an excitable reaction-diffusion system involving epidermal growth factor receptor (EGFR) signalling interacting with the proneural gene l'sc. Within this framework, a propagating transition zone emerges from molecular feedback and diffusion. Ectopic activation of EGFR signalling in clones within the neuroepithelium demonstrates that a transition wave can be excited anywhere in the tissue by inducing signalling activity, consistent with a key prediction of the model. Our model illuminates the physical and molecular underpinnings of proneural wave progression and suggests a generic mechanism for regulating the sequential differentiation of tissues.Wellcome Trust Royal Societ

Where Nothing Happened: The Experience of War Captivity and Levinas’s Concept of the ‘There Is’

This article takes as its subject matter the juridico-political space of the prisoner of war (POW) camp. It sets out to determine the nature of this space by looking at the experience of war captivity by Jewish members of the Western forces in World War II, focusing on the experience of Emmanuel Levinas, who spent 5 years in German war captivity. On the basis of a historical analysis of the conditions in which Levinas spent his time in captivity, it argues that the POW camp was a space of indifference that was determined by the legal exclusion of prisoners from both war and persecution. Held behind the stage of world events, prisoners were neither able to exercise their legal agency nor released from law into a realm of extra-legal violence. Through a close reading of Levinas’s early concept of the ‘there is’ [il y a], the article seeks to establish the impact on prisoners of prolonged confinement in such a space. It sets out how prisoners’ subjectivity dissolved in the absence of meaningful relations with others and identifies the POW camp as a space in which existence was reduced to indeterminate, impersonal being

The development and optimisation of Nanobody based electrochemical immunosensors for IgG

Biosensors are increasingly heralded for their potential to create inexpensive diagnostic devices which are sensitive, selective and easy to use. One of the key categories of biosensor are immunosensors, which have historically used antibodies as bioreceptors. Though widely used, antibodies bring inherent limitations such as variability, limited stability and their reliance on animal sources. This has led to the development of alternative immuno-reagents such as non-antibody binding proteins (NABPs). These are low molecular weight proteins which largely avoid the aforementioned advantages of antibodies. They are commonly produced by bacteria enabling the use of DNA technology to manipulate bioreceptors at the molecular level. Single chain VHHs (commonly known as nanobodies) are an antibody derived NABP adapted from camelid heavy chain antibodies which are the isolated binding domain. Whilst nanobodies have been used for diagnostic and therapeutic applications, they have limited demonstration in biosensors. In this study, both antibodies and nanobodies were used to construct a biosensor. In addition nanobody performance was optimised by introducing a novel peptide spacer. The role of nanobody orientation and spacing was thus investigated and spacer length was optimised, leading to an increase in the sensitivity of the biosensor

Impact of gastro-oesophageal reflux on microRNA expression, location and function

We have shown that miRNA expression is altered in the oesophageal squamous mucosa from individuals with gastro-oesophageal reflux and ulcerative oesophagitis. These changes in miR-143, miR-145 and miR-205 expression appear to be most pronounced in the basal layer of the oesophageal epithelium. In the context of gastro-oesophageal reflux these expression changes might influence proliferation and apoptosis and thereby regulate epithelial restoration. It is reasonable to hypothesise that they could represent early molecular events preceding the development of Barrett’s oesophagus, although proving this will require further studies as described above. Future detailed analyses of the role of these miRNAs in progression from gastro-oesophageal reflux to Barrett’s oesophagus, and then to oesophageal adenocarcinoma will be valuable, and may help in efforts to control and treat these diseases.This study was funded by a Competing Project Grant from the National Health and Medical Research Council of Australia. Cameron Smith was supported by a PROBE-NET PhD scholarship funded by a Strategic research Partnerships Grant from the Cancer Council of New South Wales

Adorno?s Grey, Taussig?s Blue: Colour, Organization and Critical Affect

In this article we seek to open up the study of affect and organization to colour. Often simply taken for granted in organizational life and usually neglected in organizational thought, colour is an affective force by default. Deploying and interweaving the languages of affect theory, critical theory, and organization studies, we discuss colour as a primary phenomenon for the study of ?critical affect?. We then trace colour?s affect in conditioning the unfolding of organization in two particular ?colour/spaces? ? Adorno?s grey and Taussig?s blue of our title ? and discuss both its ambiguity and critical potential. Finally, we ponder what colour might do to the style of an organizational scholarship attuned to affect, where sentences blur with things and forces more than they seek to represent them

Identification and Differential Expression of MicroRNAs during Metamorphosis of the Japanese Flounder (Paralichthys olivaceus)

BACKGROUND: MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs of 20-25 nucleotides that play a key role in diverse biological processes. Japanese flounder undergo dramatic metamorphosis in their early development. The metamorphosis is characterized by morphological transformation from a bilaterally symmetrical to an asymmetrical body shape concomitant with extensive morphological and physiological remodeling of organs. So far, only a few miRNAs have been identified in fish and there are very few reports about the Japanese flounder miRNA. METHODOLOGY/PRINCIPAL FINDINGS: Solexa sequencing technology was used to perform high throughput sequencing of the small RNA library from the metamorphic period of Japanese flounder. Subsequently, aligning these sequencing data with metazoan known miRNAs, we characterized 140 conserved miRNAs and 57 miRNA: miRNA* pairs from the small RNA library. Among these 57 miRNA: miRNA* pairs, twenty flounder miRNA precursors were amplified from genomic DNA. We also demonstrated evolutionary conservation of Japanese flounder miRNAs and miRNA* in the animal evolution process. Using miRNA microarrays, we identified 66 differentially expressed miRNAs at two metamorphic stages (17 and 29 days post hatching) of Japanese flounder. The results show that miRNAs might play a key role in regulating gene expression during Japanese flounder metamorphosis. CONCLUSIONS/SIGNIFICANCE: We identified a large number of miRNAs during flounder metamorphosis, some of which are differentially expressed at two different metamorphic stages. The study provides an opportunity for further understanding of miRNA function in the regulation of flounder metamorphosis and gives us clues for further studies of the mechanisms of metamorphosis in Japanese flounder

Alteration of EGFR Spatiotemporal Dynamics Suppresses Signal Transduction

The epidermal growth factor receptor (EGFR), which regulates cell growth and survival, is integral to colon tumorigenesis. Lipid rafts play a role in regulating EGFR signaling, and docosahexaenoic acid (DHA) is known to perturb membrane domain organization through changes in lipid rafts. Therefore, we investigated the mechanistic link between EGFR function and DHA. Membrane incorporation of DHA into immortalized colonocytes altered the lateral organization of EGFR. DHA additionally increased EGFR phosphorylation but paradoxically suppressed downstream signaling. Assessment of the EGFR-Ras-ERK1/2 signaling cascade identified Ras GTP binding as the locus of the DHA-induced disruption of signal transduction. DHA also antagonized EGFR signaling capacity by increasing receptor internalization and degradation. DHA suppressed cell proliferation in an EGFR-dependent manner, but cell proliferation could be partially rescued by expression of constitutively active Ras. Feeding chronically-inflamed, carcinogen-injected C57BL/6 mice a fish oil containing diet enriched in DHA recapitulated the effects on the EGFR signaling axis observed in cell culture and additionally suppressed tumor formation. We conclude that DHA-induced alteration in both the lateral and subcellular localization of EGFR culminates in the suppression of EGFR downstream signal transduction, which has implications for the molecular basis of colon cancer prevention by DHA