Functional Dicer Is Necessary for Appropriate Specification of Radial Glia during Early Development of Mouse Telencephalon

Early telencephalic development involves transformation of neuroepithelial stem cells into radial glia, which are themselves neuronal progenitors, around the time when the tissue begins to generate postmitotic neurons. To achieve this transformation, radial precursors express a specific combination of proteins. We investigate the hypothesis that micro RNAs regulate the ability of the early telencephalic progenitors to establish radial glia. We ablate functional Dicer, which is required for the generation of mature micro RNAs, by conditionally mutating the Dicer1 gene in the early embryonic telencephalon and analyse the molecular specification of radial glia as well as their progeny, namely postmitotic neurons and basal progenitors. Conditional mutation of Dicer1 from the telencephalon at around embryonic day 8 does not prevent morphological development of radial glia, but their expression of Nestin, Sox9, and ErbB2 is abnormally low. The population of basal progenitors, which are generated by the radial glia, is disorganised and expanded in Dicer1-/- dorsal telencephalon. While the proportion of cells expressing markers of postmitotic neurons is unchanged, their laminar organisation in the telencephalic wall is disrupted suggesting a defect in radial glial guided migration. We found that the laminar disruption could not be accounted for by a reduction of the population of Cajal Retzius neurons. Together, our data suggest novel roles for micro RNAs during early development of progenitor cells in the embryonic telencephalon

Early evolution of the LIM homeobox gene family

Background: LIM homeobox (Lhx) transcription factors are unique to the animal lineage and have patterning roles during embryonic development in flies, nematodes and vertebrates, with a conserved role in specifying neuronal identity. Though genes of this family have been reported in a sponge and a cnidarian, the expression patterns and functions of the Lhx family during development in non-bilaterian phyla are not known

Side-chain crystallinity and thermal transitions in thermotropic liquid crystalline poly(γ-alkyl-α,L-glutamate)s

Linear poly(γ-alkyl substituted-α,L-glutamate)s, PALG-n (where n represents the number of carbon atoms of the paraffinic side chain segment) are unusual in the ranks of synthetic polymers in having the ability to exist in well defined chain conformation of extensive order such as the helix and retain such structures even in solution. The presence of two types of units - units which participate in the formation of backbone of the main chain and units from which the side chains are constructed - is the most important property of these polymers. This duality of structure of the PALG-n macromolecule results in the dual character of the ordering and properties of the system as a whole. The objective of this paper is to analyze the melting/crystallization behavior of paraffinic segments of side chains from poly(γ-hexadecyl-α,L-glutamate), PALG-16, and poly(γ-stearyl-α,L-glutamate), PALG-18, as well as the onset of the LC state in these polymers

Structural changes in PMMA under hard X-ray irradiation

We describe here initial studies of several commercially available poly(methylmethacrylate)s, PMMAs, both before and after exposure to hard X-rays. In order to gain knowledge about the chemical changes that occur during resist preparation (gluing to substrate, etc.) and exposure, several analytical spectroscopic, chromatographic, and thermal methods have been applied. Gas Chromatography-Mass Spectrometry (GC-MS) has been used to observe in the PMMA (before and after exposure) trapped volatiles, such as MMA monomer. Thermal analysis methods were employed to gain knowledge about the effects of pre-exposure annealing of PMMA on radiation-induced swelling. In addition, gel permeation chromatography (GPC) and matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOFMS) were used to obtain information concerning polymer/oligomer characteristics

Metformin Inhibits Migration and Invasion by Suppressing ROS Production and COX2 Expression in MDA-MB-231 Breast Cancer Cells.

Background: Several mechanisms of action have been proposed to explain the apparent antineoplastic functions of metformin, many of which are observed at high concentrations that may not be reflective of achievable tissue concentrations. We propose that metformin at low concentrations functions to inhibit ROS production and inflammatory signaling in breast cancer, thereby reducing metastasis. Methods: Using the highly invasive MDA-MB-231 breast carcinoma model, we ascertained the impact of metformin on cell viability by DNA content analysis and fluorescent dye exclusion. Migration and invasion assays were performed using a modified Boyden chamber assay and metastasis was ascertained using the chorioallantoic membrane (CAM) assay. PGE2 production was measured by Enzyme-Linked Immunosorbent Assay (ELISA). COX2 and ICAM1 levels were determined by flow cytometry immunoassay. Results: Metformin acutely decreased cell viability and caused G2 cell cycle arrest only at high concentrations (10 mM). At 100 µM, however, metformin reduced ICAM1 and COX2 expression, as well as reduced PGE2 production and endogenous mitochondrial ROS production while failing to significantly impact cell viability. Consequently, metformin inhibited migration, invasion in vitro and PGE2-dependent metastasis in CAM assays. Conclusion: At pharmacologically achievable concentrations, metformin does not drastically impact cell viability, but inhibits inflammatory signaling and metastatic progression in breast cancer cells