Connectivity of Phases and Growth Mechanisms in Peritectic Alloys Solidified at Low Speed: an X-Ray Tomography Study of Cu-Sn

The variety of microstructures that form at low solidification speed in peritectic alloys, bands, and islands, or even coupled (or cooperative) growth of the primary α and peritectic β phases, have been previously explained by nucleation-growth mechanisms. In a recent investigation on Cu-Sn, a new growth mechanism was conjectured on the basis of two-dimensional (2-D) optical microscopy and electron backscattered diffraction (EBSD) observations made in longitudinal sections. In the present contribution, synchrotron-based tomographic microscopy has been used to confirm this mechanism: α and β phases totally interconnected in three dimensions and bands (or islands) can result from an overlay mechanism, rather than from a nucleation events sequence. When the lateral growth of a new layer is too fast, an instability can lead to the formation of a lamellar structure as for eutectic alloy

Conserved microRNA editing in mammalian evolution, development and disease.

BACKGROUND: Mammalian microRNAs (miRNAs) are sometimes subject to adenosine-to-inosine RNA editing, which can lead to dramatic changes in miRNA target specificity or expression levels. However, although a few miRNAs are known to be edited at identical positions in human and mouse, the evolution of miRNA editing has not been investigated in detail. In this study, we identify conserved miRNA editing events in a range of mammalian and non-mammalian species. RESULTS: We demonstrate deep conservation of several site-specific miRNA editing events, including two that date back to the common ancestor of mammals and bony fishes some 450 million years ago. We also find evidence of a recent expansion of an edited miRNA family in placental mammals and show that editing of these miRNAs is associated with changes in target mRNA expression during primate development and aging. While global patterns of miRNA editing tend to be conserved across species, we observe substantial variation in editing frequencies depending on tissue, age and disease state: editing is more frequent in neural tissues compared to heart, kidney and testis; in older compared to younger individuals; and in samples from healthy tissues compared to tumors, which together suggests that miRNA editing might be associated with a reduced rate of cell proliferation. CONCLUSIONS: Our results show that site-specific miRNA editing is an evolutionarily conserved mechanism, which increases the functional diversity of mammalian miRNA transcriptomes. Furthermore, we find that although miRNA editing is rare compared to editing of long RNAs, miRNAs are greatly overrepresented among conserved editing targets

Nkx2.1 regulates the proliferation and cell fate of telencephalic astrocytes during embryonic development

AbstractThe homeodomain transcription factor Nkx2.1 controls cell differentiation of telencephalic GABAergic interneurons and oligodendrocytes. Here, we show that Nkx2.1 additionally regulates astrogliogenesis of the telencephalon from embryonic day (E) 14.5 to E16.5. Our work aims to identify the different mechanisms by which Nkx2.1 controls telencephalic astrogliogenesis. InNkx2.1-/-, a drastic loss of astrocytes is observed which is not related to cell death.In vivoanalysis using BrdU incorporation reveals that Nkx2.1 affects the proliferation of ventral neural stem cells that generate early astrocytes.In vitroneurosphere assays show that Nkx2.1 additionally affects the differentiation step of Nkx2.1-derived astrocytes. Chromatin immunoprecipitation andin vitroco-transfection studies of a Nkx2.1-expressing plasmid indicate that Nkx2.1 binds to the promoter of astroglial differentiation gene GFAP, and regulates its expression. Hence, Nkx2.1 controls astroglial production spatiotemporally in embryos by regulating stem cell division and specification of the contributing Nkx2.1+precursors.</jats:p

Modeling of peritectic coupled growth in Cu-Sn alloys

In directional solidification experiments on hypoperitectic Cu-Sn alloys at low velocity and high thermal gradient, both lamellar and fibrous coupled peritectic growth patterns have been observed. Two phenomena that had not been observed in previous experiments on other alloy systems are investigated here with the help of different modeling approaches. The mean volume fraction of primary phase alpha,(g) over bar (alpha), as determined by X-ray microtomography, decreases with solidification distance over the entire length of the coupled zone, but is always much larger than that expected from the equilibrium phase diagram. Moreover, oscillations in (g) over bar (alpha), with a spatial periodicity approximately equal to the lamellar spacing are also observed. The first observation is explained semi-quantitatively by a simple ID diffusion model, which reveals that the onset of coupled growth occurs during the initial transient of the primary phase planar front growth. A two-dimensional phase-field model is used to monitor the subsequent microstructure evolution, and shows that the lamellar structure exhibits collective 1-lambda oscillations. In agreement with previous studies, it was found that these oscillations lead to stable coupled growth only for a limited range of the control parameters. (C) 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved

Study of twinned dendrite growth stability

Under certain thermal conditions (G approximate to 1 x 10(4) K/m, v(s) approximate to 1 x 10(-3) m/s), twinned dendrites appear in aluminum alloys and can overgrow regular columnar dendrites, provided that some convection is also present in the melt. In order to check the stability of such morphologies, directionally solidified twinned samples of Al-Zn were partially remelted in a Bridgman furnace and then resolidified under controlled conditions, with minimal convection. It was found that, although twin planes remain stable during partial remelting, non-twinned dendrites regrow during solidification. They have a crystallographic orientation given by those of the twinned and untwinned "seed" regions, and grow along preferred directions that tend to be those of normal specimens. (C) 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved

Dendrite growth in undercooled Al-rich Al-Ni melts measured on Earth and in Space

The dendrite growth velocity in Al₇₅Ni₂₅ melts has been measured in a containerless procedure as a function of undercooling using an electromagnetic levitation technique both in the Earth laboratory and in Space on board the International Space Station. The growth shows an anomalous behavior inasmuch as the growth velocity decreases with increasing undercooling, confirming previous experiments on Earth. Within the scatter of experimental data, results obtained on Earth and in Space do not show significant differences. Thus, convection effects as the origin of the anomalous growth characteristics can be excluded. However, high-speed video recording exhibits multiple nucleation events in front of the growing solid-liquid interface. This effect is identified as the origin of the anomalous dendrite growth characteristics in undercooled melts of Al-rich Al-Ni melts

The Ciliogenic Transcription Factor RFX3 Regulates Early Midline Distribution of Guidepost Neurons Required for Corpus Callosum Development

The corpus callosum (CC) is the major commissure that bridges the cerebral hemispheres. Agenesis of the CC is associated with human ciliopathies, but the origin of this default is unclear. Regulatory Factor X3 (RFX3) is a transcription factor involved in the control of ciliogenesis, and Rfx3–deficient mice show several hallmarks of ciliopathies including left–right asymmetry defects and hydrocephalus. Here we show that Rfx3–deficient mice suffer from CC agenesis associated with a marked disorganisation of guidepost neurons required for axon pathfinding across the midline. Using transplantation assays, we demonstrate that abnormalities of the mutant midline region are primarily responsible for the CC malformation. Conditional genetic inactivation shows that RFX3 is not required in guidepost cells for proper CC formation, but is required before E12.5 for proper patterning of the cortical septal boundary and hence accurate distribution of guidepost neurons at later stages. We observe focused but consistent ectopic expression of Fibroblast growth factor 8 (Fgf8) at the rostro commissural plate associated with a reduced ratio of GLIoma-associated oncogene family zinc finger 3 (GLI3) repressor to activator forms. We demonstrate on brain explant cultures that ectopic FGF8 reproduces the guidepost neuronal defects observed in Rfx3 mutants. This study unravels a crucial role of RFX3 during early brain development by indirectly regulating GLI3 activity, which leads to FGF8 upregulation and ultimately to disturbed distribution of guidepost neurons required for CC morphogenesis. Hence, the RFX3 mutant mouse model brings novel understandings of the mechanisms that underlie CC agenesis in ciliopathies

Colonoscopy is the preferred colorectal cancer screening method in a population-based program.

BACKGROUND AND STUDY AIMS: Various screening methods for colorectal cancer (CRC) are promoted by professional societies; however, few data are available about the factors that determine patient participation in screening, which is crucial to the success of population-based programs. This study aimed (i) to identify factors that determine acceptance of screening and preference of screening method, and (ii) to evaluate procedure success, detection of colorectal neoplasia, and patient satisfaction with screening colonoscopy. PATIENTS AND METHODS: Following a public awareness campaign, the population aged 50 - 80 years was offered CRC screening in the form of annual fecal occult blood tests, flexible sigmoidoscopy, a combination of both, or colonoscopy. RESULTS: 2731 asymptomatic persons (12.0 % of the target population) registered with and were eligible to take part in the screening program. Access to information and a positive attitude to screening were major determinants of participation. Colonoscopy was the method preferred by 74.8 % of participants. Advanced colorectal neoplasia was present in 8.5 %; its prevalence was higher in males and increased with age. Significant complications occurred in 0.5 % of those undergoing colonoscopy and were associated with polypectomy or sedation. Most patients were satisfied with colonoscopy and over 90 % would choose it again for CRC screening. CONCLUSIONS: In this population-based study, only a small proportion of the target population underwent CRC screening despite an extensive information campaign. Colonoscopy was the preferred method and was safe. The determinants of participation in screening and preference of screening method, together with the distribution of colorectal neoplasia in different demographic categories, provide a rationale for improving screening procedures