Optical gain in 1.3-μm electrically driven dilute nitride VCSOAs

We report the observation of room-temperature optical gain at 1.3 μm in electrically driven dilute nitride vertical cavity semiconductor optical amplifiers. The gain is calculated with respect to injected power for samples with and without a confinement aperture. At lower injected powers, a gain of almost 10 dB is observed in both samples. At injection powers over 5 nW, the gain is observed to decrease. For nearly all investigated power levels, the sample with confinement aperture gives slightly higher gain

Eutherian-specific homeobox genes in the preimplantation embryo; function, evolution, and applications.

This thesis explores the evolution, function, and possible applications of a group of lineage-specific genes known as the Eutherian Totipotent Cell Homeobox (ETCHbox) genes. The ETCHbox genes duplicated from a highly conserved vertebrate eye-specific homeobox gene called Cone-rod homeobox (CRX) in the lineage leading to eutherian mammals. The ETCHbox genes are unusual in many respects. Firstly, they are eutherian-specific, meaning that they are only present in the genomes of one group of mammals and not in marsupials or monotremes, which only have CRX. Secondly, they are highly variable in copy number and sequence, both compared to the “parental” gene from which they diverged, and between different species of eutherian mammal. Thirdly, their expression is limited to a few stages in the very early preimplantation embryo, after which they are not known to be expressed in any tissue. How can duplicates of a gene conserved in sequence and in function become so divergent so quickly, and what can their role be? I explore how the extreme divergence has evolved in eutherians, what their new functions could be, and whether their specificity for the very early embryo can be applied to the field of regenerative biology. I initially focus on the mouse genome, using ectopic expression to reveal unexpected functional overlaps between human and mouse paralogues, not orthologues, and hypothesise inferred ETCHbox function. I use sequence analysis and ectopic expression to explore the evolution of ETCHbox genes from CRX using comparisons of eutherian and marsupial homeobox genes and embryology, finding evidence for a nuanced subfunctionalisation occurring on the eutherian lineage between CRX and ETCHbox. I then continue the evolutionary approach specifically within the order Rodentia, where I find that stepwise gene losses and sequence divergences occurred. Finally, I examine the effect of ETCHbox genes on pluripotency before discussing a model for how ETCHbox complexities could evolve. Overall, I have used a blend of computational and experimental techniques to increase our understanding of ETCHbox gene evolution and function, before exploring potential applications.</p

Dynamic molecular evolution of mammalian homeobox genes: duplication, loss, divergence and gene conversion sculpt PRD class repertoires

The majority of homeobox genes are highly conserved across animals, but the eutherian-specific ETCHbox genes, embryonically expressed and highly divergent duplicates of CRX, are a notable exception. Here we compare the ETCHbox genes of 34 mammalian species, uncovering dynamic patterns of gene loss and tandem duplication, including the presence of a large tandem array of LEUTX loci in the genome of the European rabbit (Oryctolagus cuniculus). Despite extensive gene gain and loss, all sampled species possess at least two ETCHbox genes, suggesting their collective role is indispensable. We find evidence for positive selection and show that TPRX1 and TPRX2 have been the subject of repeated gene conversion across the Boreoeutheria, homogenising their sequences and preventing divergence, especially in the homeobox region. Together, these results are consistent with a model where mammalian ETCHbox genes are dynamic in evolution due to functional overlap, yet have collective indispensable roles

Of eyes and embryos: subfunctionalisation of the CRX homeobox gene in mammalian evolution

ETCHbox genes are fast-evolving homeobox genes present only in eutherian (placental) mammals which originated by duplication and divergence from a conserved homeobox gene, Cone-rod homeobox (CRX). While expression and function of CRX are restricted to the retina in eutherian mammals, ETCHbox gene expression is specific to preimplantation embryos. This dramatic difference could reflect the acquisition of new functions by duplicated genes or subfunctionalization of pleiotropic roles between CRX and ETCHbox genes. To resolve between these hypotheses, we compared expression, sequence and inferred function between CRX of metatherian (marsupial) mammals and ETCHbox genes of eutherians. We find the metatherian CRX homeobox gene is expressed in early embryos and in eyes, unlike eutherian CRX, and distinct amino acid substitutions were fixed in the metatherian and eutherian evolutionary lineages consistent with altered transcription factor specificity. We find that metatherian CRX is capable of regulating embryonically expressed genes in cultured cells in a comparable way to eutherian ETCHbox. The data are consistent with CRX having a dual role in eyes and embryos of metatherians, providing an early embryonic function comparable to that of eutherian ETCHbox genes; we propose that subfunctionalization of pleiotropic functions occurred after gene duplication along the placental lineage, followed by functional elaboration.</p

Le Petit Marocain

05 octobre 19451945/10/05 (A33,N9094)-1945/10/05

Of eyes and embryos: subfunctionalisation of the CRX homeobox gene in mammalian evolution

ETCHbox genes are fast-evolving homeobox genes present only in eutherian (placental) mammals which originated by duplication and divergence from a conserved homeobox gene,andnbsp;Cone-rod homeoboxandnbsp;(CRX). While expression and function ofandnbsp;CRXandnbsp;are restricted to the retina in eutherian mammals, ETCHbox gene expression is specific to preimplantation embryos. This dramatic difference could reflect the acquisition of new functions by duplicated genes or subfunctionalization of pleiotropic roles betweenandnbsp;CRXandnbsp;and ETCHbox genes. To resolve between these hypotheses, we compared expression, sequence and inferred function betweenandnbsp;CRXandnbsp;of metatherian (marsupial) mammals and ETCHbox genes of eutherians. We find the metatherianandnbsp;CRXandnbsp;homeobox gene is expressed in early embryos and in eyes, unlike eutherianandnbsp;CRX, and distinct amino acid substitutions were fixed in the metatherian and eutherian evolutionary lineages consistent with altered transcription factor specificity. We find that metatherianandnbsp;CRXandnbsp;is capable of regulating embryonically expressed genes in cultured cells in a comparable way to eutherian ETCHbox. The data are consistent withandnbsp;CRXandnbsp;having a dual role in eyes and embryos of metatherians, providing an early embryonic function comparable to that of eutherian ETCHbox genes; we propose that subfunctionalization of pleiotropic functions occurred after gene duplication along the placental lineage, followed by functional elaboration.</p

Modulation of endothelial monolayer permeability induced by plasma obtained from lipopolysaccharide-stimulated whole blood

The aim of this study was to elucidate the time course of the permeability response of endothelial monolayers after exposure to plasma obtained from lipopolysaccharide (LPS)-treated human whole blood; to investigate the role of apoptosis in monolayer permeability, and to inhibit the permeability increase, particularly after addition of the plasma stimulus. Human umbilical vein endothelial cells (HUVEC) were cultured on semiporous membranes and the permeability for albumin was measured after exposure, according to different schedules, to LPS-conditioned plasma. Apoptotic HUVEC were measured by both flow cytometry and ELISA. A variety of agents, including antibodies against cytokines, inhibitors of NF-κB, and a caspase inhibitor, were added to HUVEC, either prior to or after the stimulus. A maximum increase of the permeability was achieved after 4–6 h of exposure to LPS-conditioned plasma. This response was not accompanied by an increase in the number of apoptotic HUVEC. Administration of antibodies against both Tumour Necrosis Factor-α (TNF-α) and Interleukin-1β (IL-1β) to HUVEC within 1 h after stimulation significantly reduced the permeability increase. Similarly, pyrollidine di-thiocarbamate (PDTC), but not N-acetylcysteine, could prevent the permeability response, and was still effective when added within 2 h after LPS-conditioned plasma. The TNF-α/IL-1β signal present in LPS-conditioned plasma appears to increase endothelial permeability through intracellular pathways that very likely involve the activation of NF-κB. Although poststimulatory inhibition of the permeability response proves to be possible with agents such as PDTC, the window of opportunity appears very small if placed in a clinical perspective