Neural Induction in Xenopus: Requirement for Ectodermal and Endomesodermal Signals via Chordin, Noggin, β-Catenin, and Cerberus

The origin of the signals that induce the differentiation of the central nervous system (CNS) is a long-standing question in vertebrate embryology. Here we show that Xenopus neural induction starts earlier than previously thought, at the blastula stage, and requires the combined activity of two distinct signaling centers. One is the well-known Nieuwkoop center, located in dorsal-vegetal cells, which expresses Nodal-related endomesodermal inducers. The other is a blastula Chordin- and Noggin-expressing (BCNE) center located in dorsal animal cells that contains both prospective neuroectoderm and Spemann organizer precursor cells. Both centers are downstream of the early β-Catenin signal. Molecular analyses demonstrated that the BCNE center was distinct from the Nieuwkoop center, and that the Nieuwkoop center expressed the secreted protein Cerberus (Cer). We found that explanted blastula dorsal animal cap cells that have not yet contacted a mesodermal substratum can, when cultured in saline solution, express definitive neural markers and differentiate histologically into CNS tissue. Transplantation experiments showed that the BCNE region was required for brain formation, even though it lacked CNS-inducing activity when transplanted ventrally. Cell-lineage studies demonstrated that BCNE cells give rise to a large part of the brain and retina and, in more posterior regions of the embryo, to floor plate and notochord. Loss-of-function experiments with antisense morpholino oligos (MO) showed that the CNS that forms in mesoderm-less Xenopus embryos (generated by injection with Cerberus-Short [CerS] mRNA) required Chordin (Chd), Noggin (Nog), and their upstream regulator β-Catenin. When mesoderm involution was prevented in dorsal marginal-zone explants, the anterior neural tissue formed in ectoderm was derived from BCNE cells and had a complete requirement for Chd. By injecting Chd morpholino oligos (Chd-MO) into prospective neuroectoderm and Cerberus morpholino oligos (Cer-MO) into prospective endomesoderm at the 8-cell stage, we showed that both layers cooperate in CNS formation. The results suggest a model for neural induction in Xenopus in which an early blastula β-Catenin signal predisposes the prospective neuroectoderm to neural induction by endomesodermal signals emanating from Spemann's organizer

Stem cell impairment at the host–microbiota interface in colorectal cancer

Colorectal cancer (CRC) initiation is believed to result from the conversion of normal intestinal stem cells (ISCs) into cancer stem cells (CSCs), also known as tumor-initiating cells (TICs). Hence, CRC evolves through the multiple acquisition of well-established genetic and epigenetic alterations with an adenoma–carcinoma sequence progression. Unlike other stem cells elsewhere in the body, ISCs cohabit with the intestinal microbiota, which consists of a diverse community of microorganisms, including bacteria, fungi, and viruses. The gut microbiota communicates closely with ISCs and mounting evidence suggests that there is significant crosstalk between host and microbiota at the ISC niche level. Metagenomic analyses have demonstrated that the host– microbiota mutually beneficial symbiosis existing under physiologic conditions is lost during a state of pathological microbial imbalance due to the alteration of microbiota composition (dysbiosis) and/or the genetic susceptibility of the host. The complex interaction between CRC and microbiota is at the forefront of the current CRC research, and there is growing attention on a possible role of the gut microbiome in the pathogenesis of CRC through ISC niche impairment. Here we primarily review the most recent findings on the molecular mechanism underlying the complex interplay between gut microbiota and ISCs, revealing a possible key role of microbiota in the aberrant reprogramming of CSCs in the initiation of CRC. We also discuss recent advances in OMICS approaches and single-cell analyses to explore the relationship between gut microbiota and ISC/CSC niche biology leading to a desirable implementation of the current precision medicine approaches

Optical Spectroscopy of the IRAS 1-Jy Sample of Ultraluminous Infrared Galaxies

This paper discusses the optical spectroscopic properties of the IRAS 1-Jy sample of ultraluminous infrared galaxies (ULIGs). One hundred and eight of the 118 1-Jy ULIGs have been observed at dlambda = 8.3 AA resolution over the wavelength range ~4500 A -- 8900 A. These data are combined with large, previously published sets of optical spectroscopic data of lower luminosity infrared galaxies to look for systematic trends with infrared luminosity over the luminosity range L_ir ~ 10^{10.5}-10^{13} L_sun. As found in previous studies, the fraction of Seyfert galaxies among luminous infrared galaxies increases abruptly above L_ir ~ 10^{12.3} L_sun --- about 50% of the galaxies with L_ir > 10^{12.3} L_sun present Seyfert characteristics. Many of the optical and infrared spectroscopic properties of the Seyfert galaxies are consistent with the presence of a genuine active galactic nucleus (AGN). About 30% of these galaxies are Seyfert 1s with broad-line regions similar to those of optical quasars. The percentage of Seyfert 1 ULIGs increases with infrared luminosity, contrary to the predictions of the standard unification model for Seyfert galaxies. Comparisons of the broad-line luminosities of optical and obscured Seyfert 1 ULIGs with those of optically selected quasars of comparable bolometric luminosity suggest that the dominant energy source in most of these ULIGs is the same as in optical quasars, namely mass accretion onto a supermassive black hole, rather than a starburst. These results are consistent with recently published ISO, ASCA, and VLBI data. (abridged)Comment: Text and 23 figures (45 pages), Tables 1 - 6 (16 pages

Mad Is Required for Wingless Signaling in Wing Development and Segment Patterning in Drosophila

A key question in developmental biology is how growth factor signals are integrated to generate pattern. In this study we investigated the integration of the Drosophila BMP and Wingless/GSK3 signaling pathways via phosphorylations of the transcription factor Mad. Wingless was found to regulate the phosphorylation of Mad by GSK3 in vivo. In epistatic experiments, the effects of Wingless on wing disc molecular markers (senseless, distalless and vestigial) were suppressed by depletion of Mad with RNAi. Wingless overexpression phenotypes, such as formation of ectopic wing margins, were induced by Mad GSK3 phosphorylation-resistant mutant protein. Unexpectedly, we found that Mad phosphorylation by GSK3 and MAPK occurred in segmental patterns. Mad depletion or overexpression produced Wingless-like embryonic segmentation phenotypes. In Xenopus embryos, segmental border formation was disrupted by Smad8 depletion. The results show that Mad is required for Wingless signaling and for the integration of gradients of positional information

Minkowski's Object: A Starburst Triggered by a Radio Jet, Revisited

We present neutral hydrogen, ultraviolet, optical and near-infrared imaging, and optical spectroscopy, of Minkowski's Object (MO), a star forming peculiar galaxy near NGC 541. The observations strengthen evidence that star formation in MO was triggered by the radio jet from NGC 541. Key new results are the discovery of a 4.9E8 solar mass double HI cloud straddling the radio jet downstream from MO, where the jet changes direction and decollimates; strong detections of MO, also showing double structure, in UV and H-alpha; and numerous HII regions and associated clusters in MO. In UV, MO resembles the radio-aligned, rest-frame UV morphologies in many high redshift radio galaxies (HzRGs), also thought to be caused by jet-induced star formation. MO's stellar population is dominated by a 7.5 Myr-old, 1.9E7 solar mass instantaneous burst, with current star formation rate 0.52 solar masses per year (concentrated upstream from where the HI column density is high). This is unlike the jet-induced star formation in Centaurus A, where the jet interacts with pre-existing cold gas; in MO the HI may have cooled out of a warmer, clumpy intergalactic or interstellar medium as a result of jet interaction, followed by collapse of the cooling clouds and subsequent star formation (consistent with numerical simulations). Since the radio source that triggered star formation in MO is much less luminous, and therefore more common, than powerful HzRGs, and because the environment around MO is not particularly special in terms of abundant dense, cold gas, jet-induced star formation in the early universe might be even more prevalent than previously thought.Comment: 52 pages, 15 figures, accepted for publication in Ap

Status of the Cylindical-GEM project for the KLOE-2 Inner Tracker

The status of the R&D on the Cylindrical-GEM (CGEM) detector foreseen as Inner Tracker for KLOE-2, the upgrade of the KLOE experiment at the DAFNE phi-factory, will be presented. The R&D includes several activities: i) the construction and complete characterization of the full-size CGEM prototype, equipped with 650 microns pitch 1-D longitudinal strips; ii) the study of the 2-D readout with XV patterned strips and operation in magnetic field (up to 1.5T), performed with small planar prototypes in a dedicated test at the H4-SPS beam facility; iii) the characterization of the single-mask GEM technology for the realization of large-area GEM foils.Comment: 4 pages, 10 figures, Presented at Vienna Conference on Instrumentation (Feb 15-20, 2010, Vienna, Austria). Submitted to the Proceeding

Gene electrotransfer of IL-2 and IL-12 plasmids effectively eradicated murine B16.F10 melanoma

Gene therapy has become an important approach for treating cancer, and electroporation represents a technology for introducing therapeutic genes into a cell. An example of cancer gene therapy relying on gene electrotransfer is the use of immunomodulatory cytokines, such as interleukin 2 (IL-2) and 12 (IL-12), which directly stimulate immune cells at the tumour site. The aim of our study was to determine the effects of gene electrotransfer with two plasmids encoding IL-2 and IL-12 in vitro and in vivo. Two different pulse protocols, known as EP1 (600 V/cm, 5 ms, 1 Hz, 8 pulses) and EP2 (1300 V/cm, 100 µs, 1 Hz, 8 pulses), were assessed in vitro for application in subsequent in vivo experiments. In the in vivo experiment, gene electrotransfer of pIL-2 and pIL-12 using the EP1 protocol was performed in B16.F10 murine melanoma. Combined treatment of tumours using pIL2 and pIL12 induced significant tumour growth delay and 71% complete tumour regression. Furthermore, in tumours coexpressing IL-2 and IL-12, increased accumulation of dendritic cells and M1 macrophages was obtained along with the activation of proinflammatory signals, resulting in CD4 + and CD8 + T-lymphocyte recruitment and immune memory development in the mice. In conclusion, we demonstrated high antitumour efficacy of combined IL-2 and IL-12 gene electrotransfer protocols in low-immunogenicity murine B16.F10 melanoma