Malin 1: interacting galaxy pair?

Malin 1 is a unique, extraordinarily large low surface brightness galaxy. The structure and the origins of the galaxy are poorly understood. The reason for such a situation is an absence of detailed observational data, especially, of high-resolution kinematics. In this Letter we study the stellar kinematics of the inner part (r < 15 kpc) of Malin 1. We present spectroscopic arguments in favour of a small galaxy - Malin 1B - being a companion probably interacting with the main galaxy - Malin 1. This object is clearly seen in many published images of Malin 1 but is not mentioned in any astronomical databases. Malin 1B is located at the projected distance of 14 kpc from the Malin 1's nucleus and has small - 65$\pm$16 km/s - relative velocity, which we determined for the first time. We suggest that ongoing interaction with Malin 1B can explain main morphological features of the Malin 1's central region - two-armed spiral structure, a bar, and an external one-armed spiral pattern. We also investigated the large scale environment of Malin 1 and postulate that the galaxy SDSS J123708.91+142253.2 might be responsible for the formation of extended low-surface brightness envelope by means of head-on collision with Malin 1 (in the framework of collision scenario proposed by Mapelli et al. 2008). To test the collisional origins of Malin 1 global structure, more observational data and new numerical models are needed.Comment: 5 pages, 4 figures, accepted for publication in MNRA

Renal cell carcinoma in children: A clinicopathologic study

Purpose: To identify the prognostic factors, treatment, and outcome of children affected by renal cell carcinoma (RCC). Patients and Methods: The series included 41 patients (18 males and 23 females) with a median age of 124 months observed at the 11 Italian Association for Pediatric Hematology and Oncology centers from January 1973 to January 2001. Clinical data, surgical notes, pathologic findings, and summaries of therapy were taken from the charts. Results: Seven (17%) of the 41 patients had a papillary histology, and 34 (82.4%) had nonpapillary histology. Eighteen patients (43.9%) had stage I, one patient (2.4%) had stage II, two patients (4.8%) had stage IIIA, 10 patients (24.3%) had stage IIIB, and nine patients (21.9%) had stage IV disease. One patient had a bilateral involvement at diagnosis. Seven patients experienced disease recurrence. Lung and liver were the most common distant lesions and usually were fatal. In this study, the major factor influencing the prognosis was the stage. Event-free survival at 20 years was 53.5% for all patients. Overall survival at 20 years was 54.9% for all patients. Conclusion: RCC is a rare disease in children and adolescents. This neoplasm has a different clinical presentation in children compared with adults but the same outcome. In our experience, patients with localized disease could be cured by nephrectomy alone. Prospective studies in a larger number of patients are needed to confirm radiation therapy and biologic response modifiers as effective adjunct therapy in RCC stage III. The alternative therapy seems warranted in patients with advanced disease. © 2003 by American Society of Clinical Oncology

The Millennium Galaxy Catalogue: the space density and surface brightness distribution(s) of galaxies

We recover the joint and individual space density and surface brightness distribution(s) of galaxies from the Millennium Galaxy Catalogue. The MGC is a local survey spanning 30.9 sq deg and probing approximately one--two mag/sq arcsec deeper than either the Two-Degree Field Galaxy Redshift Survey (2dFGRS) or the Sloan Digital Sky Survey (SDSS). The MGC contains 10,095 galaxies to B_mgc < 20 mag with 96 per cent spectroscopic completeness. We implement a joint luminosity-surface brightness step-wise maximum likelihood method to recover the bivariate brightness distribution (BBD) inclusive of most selection effects. Integrating the BBD over surface brightness we recover the following Schechter function parameters: phi* = (0.0177 +/- 0.0015) h^3 Mpc^{-3}, M_{B}* - 5 log h = (-19.60 +/- 0.04) mag and alpha =-1.13 +/- 0.02. Compared to the 2dFGRS (Norberg et al 2002) we find a consistent M* value but a slightly flatter faint-end slope and a higher normalisation, resulting in a final luminosity density j_{b_J} = (1.99 +/- 0.17) x 10^8 h L_{odot} Mpc^{-3}. The MGC surface brightness distribution is a well bounded Gaussian at the M* point with phi* = (3.5 +/- 0.1) x 10^{-2} h^3 Mpc^{-3}, mu^{e*} = (21.90 +/- 0.01) mag/sq arcsec and sigma_{ln R_e} = 0.35 +/- 0.01. The characteristic surface brightness for luminous systems is invariant to M_{B} - 5 log h ~ -19 mag faintwards of which it moves to lower surface brightness. Higher resolution (FWHM 26 mag/sq arcsec in the B-band) observations of the local universe are now essential to probe to lower luminosity and lower surface brightness levels. [abridged]Comment: Accepted for publication in MNRAS, 26 pages with 21 figures (some degraded). A full pdf version, along with MGC data release, is available from the MGC website at, http://www.eso.org/~jliske/mg

Aberrant survival of hippocampal Cajal-Retzius cells leads to memory deficits, gamma rhythmopathies and susceptibility to seizures in adult mice

Cajal-Retzius cells (CRs) are transient neurons, disappearing almost completely in the postnatal neocortex by programmed cell death (PCD), with a percentage surviving up to adulthood in the hippocampus. Here, we evaluate CR’s role in the establishment of adult neuronal and cognitive function using a mouse model preventing Bax-dependent PCD. CRs abnormal survival resulted in impairment of hippocampus-dependent memory, associated in vivo with attenuated theta oscillations and enhanced gamma activity in the dorsal CA1. At the cellular level, we observed transient changes in the number of NPY cells and altered CA1 pyramidal cell spine density. At the synaptic level, these changes translated into enhanced inhibitory currents in hippocampal pyramidal cells. Finally, adult mutants displayed an increased susceptibility to lethal tonic-clonic seizures in a kainate model of epilepsy. Our data reveal that aberrant survival of a small proportion of postnatal hippocampal CRs results in cognitive deficits and epilepsy-prone phenotypes in adulthood.We thank Dr. P. Billuart for critical reading of the manuscript and suggestions during the course of the study, the NeuroImag platform at the IPNP and SFR Necker Imaging and histology platforms at the Imagine Institute for help with acquisition, the animal house facility (LEAT) and Animalliance for animal care. We are grateful to N. Ramezanidoraki and P. Billuart for initiating the first MEA experiment as well as members of the Pierani’s lab for technical support and helpful discussions.We thank Ann Kennedy for mouse profile (Zenodo, 2020) doi:10.5281/zenodo.3925921and for the mouse scheme in Fig. 3a, French Ministry of Research (BioSPc Doctoral school) (M.R.), Fondation pour la recherche médicale, FDT20201201037 (M.R.), Centre national de la recherche scientifique (CNRS) (A.P.), Agence Nationale de la Recherche, ANR-15-CE16-0003-01, ANR-19-CE16-0017-03 and ANR20-CE16-0001-01 (A.P.), Fondation pour la recherche médicale, Équipe FRM DEQ20130326521 and EQU201903007836) (A.P.), Agence Nationale de la Recherche under “Investissements d’avenir” program, ANR10-IAHU-01) (Imagine Institute), Fondation pour la recherche médicale (F.O.), AGEMED-INSERM (F.O.), NRJ for Neuroscience (F.O.), European Research Council (Consolidator grant #683154) (N. Rouach), European Research Council (Starting Grant #678250) (N. Rebola), Agence Nationale de la Recherche ANR-21-CE16-0020 and ANR-20-CE16-0009 (N. Rebola), and ANR-21-NEU2-0007-01 Eranet-Neuron ROSSINI project (A.P. and L.M.d.l.P.)

Clinical, immunological, and molecular features of typical and atypical severe combined immunodeficiency: Report of the italian primary immunodeficiency network

Severe combined immunodeficiencies (SCIDs) are a group of inborn errors of the immune system, usually associated with severe or life-threatening infections. Due to the variability of clinical phenotypes, the diagnostic complexity and the heterogeneity of the genetic basis, they are often difficult to recognize, leading to a significant diagnostic delay (DD). Aim of this study is to define presenting signs and natural history of SCID in a large cohort of patients, prior to hematopoietic stem cell or gene therapies. To this purpose, we conducted a 30-year retro-prospective multicenter study within the Italian Primary Immunodeficiency Network. One hundred eleven patients, diagnosed as typical or atypical SCID according to the European Society for Immune Deficiencies criteria, were included. Patients were subsequently classified based on the genetic alteration, pathogenic mechanism and immunological classification. A positive relationship between the age at onset and the DD was found. SCID patients with later onset were identified only in the last decade of observation. Syndromic SCIDs represented 28% of the cohort. Eight percent of the subjects were diagnosed in Intensive Care Units. Fifty-three percent had an atypical phenotype and most of them exhibited a discordant genotype-immunophenotype. Pre-treatment mortality was higher in atypical and syndromic patients. Our study broadens the knowledge of clinical and laboratory manifestations and genotype/phenotype correlation in patients with SCID and may facilitate the diagnosis of both typical and atypical forms of the disease in countries where newborn screening programs have not yet been implemented

Dynamic Assignment and Maintenance of Positional Identity in the Ventral Neural Tube by the Morphogen Sonic Hedgehog

During development of the vertebrate neural tube, cells acquire their positional identity from not only the spatial level of the Sonic Hedgehog signaling gradient, but also the temporal duration

Threshold-Dependent BMP-Mediated Repression: A Model for a Conserved Mechanism That Patterns the Neuroectoderm

Subdivision of the neuroectoderm into three rows of cells along the dorsal-ventral axis by neural identity genes is a highly conserved developmental process. While neural identity genes are expressed in remarkably similar patterns in vertebrates and invertebrates, previous work suggests that these patterns may be regulated by distinct upstream genetic pathways. Here we ask whether a potential conserved source of positional information provided by the BMP signaling contributes to patterning the neuroectoderm. We have addressed this question in two ways: First, we asked whether BMPs can act as bona fide morphogens to pattern the Drosophila neuroectoderm in a dose-dependent fashion, and second, we examined whether BMPs might act in a similar fashion in patterning the vertebrate neuroectoderm. In this study, we show that graded BMP signaling participates in organizing the neural axis in Drosophila by repressing expression of neural identity genes in a threshold-dependent fashion. We also provide evidence for a similar organizing activity of BMP signaling in chick neural plate explants, which may operate by the same double negative mechanism that acts earlier during neural induction. We propose that BMPs played an ancestral role in patterning the metazoan neuroectoderm by threshold-dependent repression of neural identity genes

A Novel Role for Dbx1-Derived Cajal-Retzius Cells in Early Regionalization of the Cerebral Cortical Neuroepithelium

Patterning of the cerebral cortex during embryogenesis depends not only on passive diffusion of morphogens but also on signal delivery by Cajal-Retzius neurons that migrate over long distances

Systems Biology of the Clock in Neurospora crassa

A model-driven discovery process, Computing Life, is used to identify an ensemble of genetic networks that describe the biological clock. A clock mechanism involving the genes white-collar-1 and white-collar-2 (wc-1 and wc-2) that encode a transcriptional activator (as well as a blue-light receptor) and an oscillator frequency (frq) that encodes a cyclin that deactivates the activator is used to guide this discovery process through three cycles of microarray experiments. Central to this discovery process is a new methodology for the rational design of a Maximally Informative Next Experiment (MINE), based on the genetic network ensemble. In each experimentation cycle, the MINE approach is used to select the most informative new experiment in order to mine for clock-controlled genes, the outputs of the clock. As much as 25% of the N. crassa transcriptome appears to be under clock-control. Clock outputs include genes with products in DNA metabolism, ribosome biogenesis in RNA metabolism, cell cycle, protein metabolism, transport, carbon metabolism, isoprenoid (including carotenoid) biosynthesis, development, and varied signaling processes. Genes under the transcription factor complex WCC ( = WC-1/WC-2) control were resolved into four classes, circadian only (612 genes), light-responsive only (396), both circadian and light-responsive (328), and neither circadian nor light-responsive (987). In each of three cycles of microarray experiments data support that wc-1 and wc-2 are auto-regulated by WCC. Among 11,000 N. crassa genes a total of 295 genes, including a large fraction of phosphatases/kinases, appear to be under the immediate control of the FRQ oscillator as validated by 4 independent microarray experiments. Ribosomal RNA processing and assembly rather than its transcription appears to be under clock control, suggesting a new mechanism for the post-transcriptional control of clock-controlled genes