miR-9 Acts as an OncomiR in Prostate Cancer through Multiple Pathways That Drive Tumour Progression and Metastasis

Identification of dysregulated microRNAs (miRNAs) in prostate cancer is critical not only for diagnosis, but also differentiation between the aggressive and indolent forms of the disease. miR-9 was identified as an oncomiR through both miRNA panel RT-qPCR as well as high-throughput sequencing analysis of the human P69 prostate cell line as compared to its highly tumorigenic and metastatic subline M12, and found to be consistently upregulated in other prostate cell lines including DU-145 and PC3. While miR-9 has been characterized as dysregulated either as an oncomiR or tumour suppressor in a variety of other cancers including breast, ovarian, and nasopharyngeal carcinomas, it has not been previously evaluated and proven as an oncomiR in prostate cancer. miR-9 was confirmed an oncomiR when found to be overexpressed in tumour tissue as compared to adjacent benign glandular epithelium through laser-capture microdissection of radical prostatectomy biopsies. Inhibition of miR-9 resulted in reduced migratory and invasive potential of the M12 cell line, and reduced tumour growth and metastases in male athymic nude mice. Analysis showed that miR-9 targets e-cadherin and suppressor of cytokine signalling 5 (SOCS5), but not NF-ĸB mRNA. Expression of these proteins was shown to be affected by modulation in expression of miR-9

The secreted neurotrophin Spatzle 3 promotes glial morphogenesis and supports neuronal survival and function

Most glial functions depend on establishing intimate morphological relationships with neurons. Significant progress has been made in understanding neuron-glia signaling at synaptic and axonal contacts, but how glia support neuronal cell bodies is unclear. Here we explored the growth and functions of Drosophila cortex glia (which associate almost exclusively with neuronal cell bodies) to understand glia-soma interactions. We show that cortex glia tile with one another and with astrocytes to establish unique central nervous system (CNS) spatial domains that actively restrict glial growth, and selective ablation of cortex glia causes animal lethality. In an RNAi-based screen, we identified alphaSNAP (soluble NSF [N-ethylmalemeide-sensitive factor] attachment protein alpha) and several components of vesicle fusion and recycling machinery as essential for the maintenance of cortex glial morphology and continued contact with neurons. Interestingly, loss of the secreted neurotrophin Spatzle 3 (Spz3) phenocopied alphaSNAP phenotypes, which included loss of glial ensheathment of neuron cell bodies, increased neuronal cell death, and defects in animal behavior. Rescue experiments suggest that Spz3 can exert these effects only over very short distances. This work identifies essential roles for glial ensheathment of neuronal cell bodies in CNS homeostasis as well as Spz3 as a novel signaling factor required for maintenance of cortex glial morphology and neuron-glia contact

Singular and regular solutions of a non-linear parabolic system

We study a dissipative nonlinear equation modelling certain features of the Navier-Stokes equations. We prove that the evolution of radially symmetric compactly supported initial data does not lead to singularities in dimensions $n\leq 4$. For dimensions $n>4$ we present strong numerical evidence supporting existence of blow-up solutions. Moreover, using the same techniques we numerically confirm a conjecture of Lepin regarding existence of self-similar singular solutions to a semi-linear heat equation.Comment: 16 page

Floating stones off El Hierro, Canary Islands: xenoliths of pre-island sedimentary origin in the early products of the October 2011 eruption

The eruption that started off the south coast of El Hierro, Canary Islands, in October 2011 has emitted intriguing eruption products found floating in the sea. These specimens appeared as floating volcanic "bombs" that have in the meantime been termed "restingolites" (after the close-by village of La Restinga) and exhibit cores of white and porous pumice-like material. Currently the nature and origin of these "floating stones" is vigorously debated among researchers, with important implications for the interpretation of the hazard potential of the ongoing eruption. The "restingolites" have been proposed to be either (i) juvenile high-silica magma (e.g. rhyolite), (ii) remelted magmatic material (trachyte), (iii) altered volcanic rock, or (iv) reheated hyaloclastites or zeolite from the submarine slopes of El Hierro. Here, we provide evidence that supports yet a different conclusion. We have collected and analysed the structure and composition of samples and compared the results to previous work on similar rocks found in the archipelago. Based on their high silica content, the lack of igneous trace element signatures, and the presence of remnant quartz crystals, jasper fragments and carbonate relicts, we conclude that "restingolites" are in fact xenoliths from pre-island sedimentary rocks that were picked up and heated by the ascending magma causing them to partially melt and vesiculate. They hence represent messengers from depth that help us to understand the interaction between ascending magma and crustal lithologies in the Canary Islands as well as in similar Atlantic islands that rest on sediment/covered ocean crust (e.g. Cape Verdes, Azores). The occurrence of these "restingolites" does therefore not indicate the presence of an explosive high-silica magma that is involved in the ongoing eruption

Absence of erythrocyte sequestration in a case of babesiosis in a splenectomized human patient

BACKGROUND: The importance of vascular occlusion in the pathogenesis of human haemoprotozoal disease is unresolved. METHODS: Giemsa-stained tissue sections from a human case of Babesia microti infection in a splenectomized patient with chronic lymphocytic leukaemia and colon cancer were examined to ascertain the distribution of parasitized erythrocytes within the vascular lumen. RESULTS: No evidence of sequestration was observed. CONCLUSION: This first report on the vascular location of B. microti in human tissue suggests that severe multi-organ failure due to babesiosis is independent of sequestration of parasitized erythrocytes. A similar pathogenesis may also cause multi-organ failure in other intraerythrocytic protozoal infections, including falciparum malaria

A High Statistics Search for Electron-Neutrino --> Tau-Neutrino Oscillations

We present new limits on nu_e to nu_tau and nu_e to nu_sterile oscillations by searching for electron neutrino dissappearance in the high-energy wide-band CCFR neutrino beam. Sensitivity to nu_tau appearance comes from tau decay modes in which a large fraction of the energy deposited is electromagnetic. The beam is composed primarily of muon neutrinos but this analysis uses the 2.3% electron neutrino component of the beam. Electron neutrino energies range from 30 to 600 GeV and flight lengths vary from 0.9 to 1.4 km. This limit improves the sensitivity of existing limits and obtains a lowest 90% confidence upper limit in sin**2(2*alpha) of 9.9 x 10**(-2) at delta-m**2 of 125 eV**2.Comment: submitted to Phys. Rev. D. Rapid Com