399 research outputs found
Brain MRI and biological diagnosis in five Tunisians MLD patients
Metachromatic leukodystrophy (MLD) is a recessive autosomal disease which is characterized by an accumulation of sulfatides in the central and peripheral nervous system. It is due to the enzyme deficiency of the sulfatide sulfatase i.e. arylsulfatase A (ASA). we studied 5/200 cases of MLD and clearly distinguished three clinical forms. One of them presented the juvenile form; two presented the late infantile form; and two other presented the adult form. The Magnetic Resonance Imaging (MRI) of these patients showed a diffuse, bilateral and symmetrical demyelination. The biochemical diagnosis of MLD patients evidencing the low activity of ASA and sulfatide accumulation
Population Carrier Rates of Pathogenic ARSA Gene Mutations: Is Metachromatic Leukodystrophy Underdiagnosed?
BACKGROUND: Metachromatic leukodystrophy (MLD) is a severe neurometabolic disease caused mainly by deficiency of arylsulfatase A encoded by the ARSA gene. Based on epidemiological surveys the incidence of MLD per 100,000 live births varied from 0.6 to 2.5. Our purpose was to estimate the birth prevalence of MLD in Poland by determining population frequency of the common pathogenic ARSA gene mutations and to compare this estimate with epidemiological data. METHODOLOGY: We studied two independently ascertained cohorts from the Polish background population (N∼3000 each) and determined carrier rates of common ARSA gene mutations: c.459+1G>A, p.P426L, p.I179S (cohort 1) and c.459+1G>A, p.I179S (cohort 2). PRINCIPAL FINDINGS: Taking into account ARSA gene mutation distribution among 60 Polish patients, the expected MLD birth prevalence in the general population (assuming no selection against homozygous fetuses) was estimated as 4.0/100,000 and 4.1/100,000, respectively for the 1(st) and the 2(nd) cohort with a pooled estimate of 4.1/100,000 (CI: 1.8-9.4) which was higher than the estimate of 0.38 per 100,000 live births based on diagnosed cases. The p.I179S mutation was relatively more prevalent among controls than patients (OR = 3.6, P = 0.0082, for a comparison of p.I179S frequency relative to c.459+1G>A between controls vs. patients). CONCLUSIONS/SIGNIFICANCE: The observed discrepancy between the measured incidence of metachromatic leukodystrophy and the predicted carriage rates suggests that MLD is substantially underdiagnosed in the Polish population. The underdiagnosis rate may be particularly high among patients with p.I179S mutation whose disease is characterized mainly by psychotic symptoms
ER stress protein AGR2 precedes and is involved in the regulation of pancreatic cancer initiation
The work was supported by a grant A12008 from CR-UK (L. Dumartin, N.R. Lemoine and T. Crnogorac-Jurcevic)
Imaging and imagination: understanding the endo-lysosomal system
Lysosomes are specialized compartments for the degradation of endocytosed and intracellular material and essential regulators of cellular homeostasis. The importance of lysosomes is illustrated by the rapidly growing number of human disorders related to a defect in lysosomal functioning. Here, we review current insights in the mechanisms of lysosome biogenesis and protein sorting within the endo-lysosomal system. We present increasing evidence for the existence of parallel pathways for the delivery of newly synthesized lysosomal proteins directly from the trans-Golgi network (TGN) to the endo-lysosomal system. These pathways are either dependent or independent of mannose 6-phosphate receptors and likely involve multiple exits for lysosomal proteins from the TGN. In addition, we discuss the different endosomal intermediates and subdomains that are involved in sorting of endocytosed cargo. Throughout our review, we highlight some examples in the literature showing how imaging, especially electron microscopy, has made major contributions to our understanding of the endo-lysosomal system today
Search of the early O3 LIGO data for continuous gravitational waves from the Cassiopeia A and Vela Jr. supernova remnants
partially_open1412sìWe present directed searches for continuous gravitational waves from the neutron stars in the Cassiopeia A (Cas A) and Vela Jr. supernova remnants. We carry out the searches in the LIGO detector data from the first six months of the third Advanced LIGO and Virgo observing run using the weave semicoherent method, which sums matched-filter detection-statistic values over many time segments spanning the observation period. No gravitational wave signal is detected in the search band of 20–976 Hz for assumed source ages greater than 300 years for Cas A and greater than 700 years for Vela Jr. Estimates from simulated continuous wave signals indicate we achieve the most sensitive results to date across the explored parameter space volume, probing to strain magnitudes as low as
∼6.3×10^−26 for Cas A and ∼5.6×10^−26 for Vela Jr. at frequencies near 166 Hz at 95% efficiency.openAbbott, R.; Abbott, T. D.; Acernese, F.; Ackley, K.; Adams, C.; Adhikari, N.; Adhikari, R. X.; Adya, V. B.; Affeldt, C.; Agarwal, D.; Agathos, M.; Agatsuma, K.; Aggarwal, N.; Aguiar, O. D.; Aiello, L.; Ain, A.; Ajith, P.; Albanesi, S.; Allocca, A.; Altin, P. A.; Amato, A.; Anand, C.; Anand, S.; Ananyeva, A.; Anderson, S. B.; Anderson, W. G.; Andrade, T.; Andres, N.; Andrić, T.; Angelova, S. V.; Ansoldi, S.; Antelis, J. M.; Antier, S.; Appert, S.; Arai, K.; Araya, M. C.; Areeda, J. S.; Arène, M.; Arnaud, N.; Aronson, S. M.; Arun, K. G.; Asali, Y.; Ashton, G.; Assiduo, M.; Aston, S. M.; Astone, P.; Aubin, F.; Austin, C.; Babak, S.; Badaracco, F.; Bader, M. K. M.; Badger, C.; Bae, S.; Baer, A. M.; Bagnasco, S.; Bai, Y.; Baird, J.; Ball, M.; Ballardin, G.; Ballmer, S. W.; Balsamo, A.; Baltus, G.; Banagiri, S.; Bankar, D.; Barayoga, J. C.; Barbieri, C.; Barish, B. C.; Barker, D.; Barneo, P.; Barone, F.; Barr, B.; Barsotti, L.; Barsuglia, M.; Barta, D.; Bartlett, J.; Barton, M. A.; Bartos, I.; Bassiri, R.; Basti, A.; Bawaj, M.; Bayley, J. C.; Baylor, A. C.; Bazzan, M.; Bécsy, B.; Bedakihale, V. M.; Bejger, M.; Belahcene, I.; Benedetto, V.; Beniwal, D.; Bennett, T. F.; Bentley, J. D.; BenYaala, M.; Bergamin, F.; Berger, B. K.; Bernuzzi, S.; Bersanetti, D.; Bertolini, A.; Betzwieser, J.; Beveridge, D.; Bhandare, R.; Bhardwaj, U.; Bhattacharjee, D.; Bhaumik, S.; Bilenko, I. A.; Billingsley, G.; Bini, S.; Birney, R.; Birnholtz, O.; Biscans, S.; Bischi, M.; Biscoveanu, S.; Bisht, A.; Biswas, B.; Bitossi, M.; Bizouard, M.-A.; Blackburn, J. K.; Blair, C. D.; Blair, D. G.; Blair, R. M.; Bobba, F.; Bode, N.; Boer, M.; Bogaert, G.; Boldrini, M.; Bonavena, L. D.; Bondu, F.; Bonilla, E.; Bonnand, R.; Booker, P.; Boom, B. A.; Bork, R.; Boschi, V.; Bose, N.; Bose, S.; Bossilkov, V.; Boudart, V.; Bouffanais, Y.; Bozzi, A.; Bradaschia, C.; Brady, P. 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A.; Dietrich, T.; Di Fiore, L.; Di Fronzo, C.; Di Giorgio, C.; Di Giovanni, F.; Di Giovanni, M.; Di Girolamo, T.; Di Lieto, A.; Ding, B.; Di Pace, S.; Di Palma, I.; Di Renzo, F.; Divakarla, A. K.; Dmitriev, A.; Doctor, Z.; D’Onofrio, L.; Donovan, F.; Dooley, K. L.; Doravari, S.; Dorrington, I.; Drago, M.; Driggers, J. C.; Drori, Y.; Ducoin, J.-G.; Dupej, P.; Durante, O.; D’Urso, D.; Duverne, P.-A.; Dwyer, S. E.; Eassa, C.; Easter, P. J.; Ebersold, M.; Eckhardt, T.; Eddolls, G.; Edelman, B.; Edo, T. B.; Edy, O.; Effler, A.; Eichholz, J.; Eikenberry, S. S.; Eisenmann, M.; Eisenstein, R. A.; Ejlli, A.; Engelby, E.; Errico, L.; Essick, R. C.; Estellés, H.; Estevez, D.; Etienne, Z.; Etzel, T.; Evans, M.; Evans, T. M.; Ewing, B. E.; Fafone, V.; Fair, H.; Fairhurst, S.; Farah, A. M.; Farinon, S.; Farr, B.; Farr, W. M.; Farrow, N. W.; Fauchon-Jones, E. J.; Favaro, G.; Favata, M.; Fays, M.; Fazio, M.; Feicht, J.; Fejer, M. M.; Fenyvesi, E.; Ferguson, D. L.; Fernandez-Galiana, A.; Ferrante, I.; Ferreira, T. A.; Fidecaro, F.; Figura, P.; Fiori, I.; Fishbach, M.; Fisher, R. P.; Fittipaldi, R.; Fiumara, V.; Flaminio, R.; Floden, E.; Fong, H.; Font, J. A.; Fornal, B.; Forsyth, P. W. F.; Franke, A.; Frasca, S.; Frasconi, F.; Frederick, C.; Freed, J. P.; Frei, Z.; Freise, A.; Frey, R.; Fritschel, P.; Frolov, V. V.; Fronzé, G. G.; Fulda, P.; Fyffe, M.; Gabbard, H. A.; Gadre, B. U.; Gair, J. R.; Gais, J.; Galaudage, S.; Gamba, R.; Ganapathy, D.; Ganguly, A.; Gaonkar, S. G.; Garaventa, B.; García-Núñez, C.; García-Quirós, C.; Garufi, F.; Gateley, B.; Gaudio, S.; Gayathri, V.; Gemme, G.; Gennai, A.; George, J.; Gerberding, O.; Gergely, L.; Gewecke, P.; Ghonge, S.; Ghosh, Abhirup; Ghosh, Archisman; Ghosh, Shaon; Ghosh, Shrobana; Giacomazzo, B.; Giacoppo, L.; Giaime, J. A.; Giardina, K. D.; Gibson, D. R.; Gier, C.; Giesler, M.; Giri, P.; Gissi, F.; Glanzer, J.; Gleckl, A. E.; Godwin, P.; Goetz, E.; Goetz, R.; Gohlke, N.; Goncharov, B.; González, G.; Gopakumar, A.; Gosselin, M.; Gouaty, R.; Gould, D. W.; Grace, B.; Grado, A.; Granata, M.; Granata, V.; Grant, A.; Gras, S.; Grassia, P.; Gray, C.; Gray, R.; Greco, G.; Green, A. C.; Green, R.; Gretarsson, A. M.; Gretarsson, E. M.; Griffith, D.; Griffiths, W.; Griggs, H. L.; Grignani, G.; Grimaldi, A.; Grimm, S. J.; Grote, H.; Grunewald, S.; Gruning, P.; Guerra, D.; Guidi, Gianluca; Guimaraes, A. R.; Guixé, G.; Gulati, H. K.; Guo, H.-K.; Guo, Y.; Gupta, Anchal; Gupta, Anuradha; Gupta, P.; Gustafson, E. K.; Gustafson, R.; Guzman, F.; Haegel, L.; Halim, O.; Hall, E. D.; Hamilton, E. Z.; Hammond, G.; Haney, M.; Hanks, J.; Hanna, C.; Hannam, M. D.; Hannuksela, O.; Hansen, H.; Hansen, T. J.; Hanson, J.; Harder, T.; Hardwick, T.; Haris, K.; Harms, J.; Harry, G. M.; Harry, I. W.; Hartwig, D.; Haskell, B.; Hasskew, R. K.; Haster, C.-J.; Haughian, K.; Hayes, F. J.; Healy, J.; Heidmann, A.; Heidt, A.; Heintze, M. C.; Heinze, J.; Heinzel, J.; Heitmann, H.; Hellman, F.; Hello, P.; Helmling-Cornell, A. F.; Hemming, G.; Hendry, M.; Heng, I. S.; Hennes, E.; Hennig, J.; Hennig, M. H.; Hernandez, A. G.; Vivanco, F. Hernandez; Heurs, M.; Hild, S.; Hill, P.; Hines, A. S.; Hochheim, S.; Hofman, D.; Hohmann, J. N.; Holcomb, D. G.; Holland, N. A.; Hollows, I. J.; Holmes, Z. J.; Holt, K.; Holz, D. E.; Hopkins, P.; Hough, J.; Hourihane, S.; Howell, E. J.; Hoy, C. G.; Hoyland, D.; Hreibi, A.; Hsu, Y.; Huang, Y.; Hübner, M. T.; Huddart, A. D.; Hughey, B.; Hui, V.; Husa, S.; Huttner, S. H.; Huxford, R.; Huynh-Dinh, T.; Idzkowski, B.; Iess, A.; Ingram, C.; Isi, M.; Isleif, K.; Iyer, B. R.; JaberianHamedan, V.; Jacqmin, T.; Jadhav, S. J.; Jadhav, S. P.; James, A. L.; Jan, A. Z.; Jani, K.; Janquart, J.; Janssens, K.; Janthalur, N. N.; Jaranowski, P.; Jariwala, D.; Jaume, R.; Jenkins, A. C.; Jenner, K.; Jeunon, M.; Jia, W.; Johns, G. R.; Jones, A. W.; Jones, D. I.; Jones, J. D.; Jones, P.; Jones, R.; Jonker, R. J. G.; Ju, L.; Junker, J.; Juste, V.; Kalaghatgi, C. V.; Kalogera, V.; Kamai, B.; Kandhasamy, S.; Kang, G.; Kanner, J. B.; Kao, Y.; Kapadia, S. J.; Kapasi, D. P.; Karat, S.; Karathanasis, C.; Karki, S.; Kashyap, R.; Kasprzack, M.; Kastaun, W.; Katsanevas, S.; Katsavounidis, E.; Katzman, W.; Kaur, T.; Kawabe, K.; Kéfélian, F.; Keitel, D.; Key, J. S.; Khadka, S.; Khalili, F. Y.; Khan, S.; Khazanov, E. A.; Khetan, N.; Khursheed, M.; Kijbunchoo, N.; Kim, C.; Kim, J. C.; Kim, K.; Kim, W. S.; Kim, Y.-M.; Kimball, C.; Kinley-Hanlon, M.; Kirchhoff, R.; Kissel, J. S.; Kleybolte, L.; Klimenko, S.; Knee, A. M.; Knowles, T. D.; Knyazev, E.; Koch, P.; Koekoek, G.; Koley, S.; Kolitsidou, P.; Kolstein, M.; Komori, K.; Kondrashov, V.; Kontos, A.; Koper, N.; Korobko, M.; Kovalam, M.; Kozak, D. B.; Kringel, V.; Krishnendu, N. V.; Królak, A.; Kuehn, G.; Kuei, F.; Kuijer, P.; Kumar, A.; Kumar, P.; Kumar, Rahul; Kumar, Rakesh; Kuns, K.; Kuwahara, S.; Lagabbe, P.; Laghi, D.; Lalande, E.; Lam, T. L.; Lamberts, A.; Landry, M.; Lane, B. B.; Lang, R. N.; Lange, J.; Lantz, B.; La Rosa, I.; Lartaux-Vollard, A.; Lasky, P. D.; Laxen, M.; Lazzarini, A.; Lazzaro, C.; Leaci, P.; Leavey, S.; Lecoeuche, Y. K.; Lee, H. M.; Lee, H. W.; Lee, J.; Lee, K.; Lehmann, J.; Lemaître, A.; Leroy, N.; Letendre, N.; Levesque, C.; Levin, Y.; Leviton, J. N.; Leyde, K.; Li, A. K. Y.; Li, B.; Li, J.; Li, T. G. F.; Li, X.; Linde, F.; Linker, S. D.; Linley, J. N.; Littenberg, T. B.; Liu, J.; Liu, K.; Liu, X.; Llamas, F.; Llorens-Monteagudo, M.; Lo, R. K. L.; Lockwood, A.; London, L. T.; Longo, A.; Lopez, D.; Portilla, M. Lopez; Lorenzini, M.; Loriette, V.; Lormand, M.; Losurdo, G.; Lott, T. P.; Lough, J. D.; Lousto, C. O.; Lovelace, G.; Lucaccioni, J. F.; Lück, H.; Lumaca, D.; Lundgren, A. P.; Lynam, J. E.; Macas, R.; MacInnis, M.; Macleod, D. M.; MacMillan, I. A. O.; Macquet, A.; Hernandez, I. Magaña; Magazzù, C.; Magee, R. M.; Maggiore, R.; Magnozzi, M.; Mahesh, S.; Majorana, E.; Makarem, C.; Maksimovic, I.; Maliakal, S.; Malik, A.; Man, N.; Mandic, V.; Mangano, V.; Mango, J. L.; Mansell, G. L.; Manske, M.; Mantovani, M.; Mapelli, M.; Marchesoni, F.; Marion, F.; Mark, Z.; Márka, S.; Márka, Z.; Markakis, C.; Markosyan, A. S.; Markowitz, A.; Maros, E.; Marquina, A.; Marsat, S.; Martelli, F.; Martin, I. W.; Martin, R. M.; Martinez, M.; Martinez, V. A.; Martinez, V.; Martinovic, K.; Martynov, D. V.; Marx, E. J.; Masalehdan, H.; Mason, K.; Massera, E.; Masserot, A.; Massinger, T. J.; Masso-Reid, M.; Mastrogiovanni, S.; Matas, A.; Mateu-Lucena, M.; Matichard, F.; Matiushechkina, M.; Mavalvala, N.; McCann, J. J.; McCarthy, R.; McClelland, D. E.; McClincy, P. K.; McCormick, S.; McCuller, L.; McGhee, G. I.; McGuire, S. C.; McIsaac, C.; McIver, J.; McRae, T.; McWilliams, S. T.; Meacher, D.; Mehmet, M.; Mehta, A. K.; Meijer, Q.; Melatos, A.; Melchor, D. A.; Mendell, G.; Menendez-Vazquez, A.; Menoni, C. S.; Mercer, R. A.; Mereni, L.; Merfeld, K.; Merilh, E. L.; Merritt, J. D.; Merzougui, M.; Meshkov, S.; Messenger, C.; Messick, C.; Meyers, P. M.; Meylahn, F.; Mhaske, A.; Miani, A.; Miao, H.; Michaloliakos, I.; Michel, C.; Middleton, H.; Milano, L.; Miller, A.; Miller, A. L.; Miller, B.; Millhouse, M.; Mills, J. C.; Milotti, E.; Minazzoli, O.; Minenkov, Y.; Mir, Ll. M.; Miravet-Tenés, M.; Mishra, C.; Mishra, T.; Mistry, T.; Mitra, S.; Mitrofanov, V. P.; Mitselmakher, G.; Mittleman, R.; Mo, Geoffrey; Moguel, E.; Mogushi, K.; Mohapatra, S. R. P.; Mohite, S. R.; Molina, I.; Molina-Ruiz, M.; Mondin, M.; Montani, M.; Moore, C. J.; Moraru, D.; Morawski, F.; More, A.; Moreno, C.; Moreno, G.; Morisaki, S.; Mours, B.; Mow-Lowry, C. M.; Mozzon, S.; Muciaccia, F.; Mukherjee, Arunava; Mukherjee, D.; Mukherjee, Soma; Mukherjee, Subroto; Mukherjee, Suvodip; Mukund, N.; Mullavey, A.; Munch, J.; Muñiz, E. A.; Murray, P. G.; Musenich, R.; Muusse, S.; Nadji, S. 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Population of Merging Compact Binaries Inferred Using Gravitational Waves through GWTC-3
We report on the population properties of compact binary mergers inferred from gravitational-wave observations of these systems during the first three LIGO-Virgo observing runs. The Gravitational-Wave Transient Catalog 3 (GWTC-3) contains signals consistent with three classes of binary mergers: binary black hole, binary neutron star, and neutron star-black hole mergers. We infer the binary neutron star merger rate to be between 10 and 1700 Gpc-3 yr-1 and the neutron star-black hole merger rate to be between 7.8 and 140 Gpc-3 yr-1, assuming a constant rate density in the comoving frame and taking the union of 90% credible intervals for methods used in this work. We infer the binary black hole merger rate, allowing for evolution with redshift, to be between 17.9 and 44 Gpc-3 yr-1 at a fiducial redshift (z=0.2). The rate of binary black hole mergers is observed to increase with redshift at a rate proportional to (1+z)κ with κ=2.9-1.8+1.7 for z≲1. Using both binary neutron star and neutron star-black hole binaries, we obtain a broad, relatively flat neutron star mass distribution extending from 1.2-0.2+0.1 to 2.0-0.3+0.3M⊙. We confidently determine that the merger rate as a function of mass sharply declines after the expected maximum neutron star mass, but cannot yet confirm or rule out the existence of a lower mass gap between neutron stars and black holes. We also find the binary black hole mass distribution has localized over- and underdensities relative to a power-law distribution, with peaks emerging at chirp masses of 8.3-0.5+0.3 and 27.9-1.8+1.9M⊙. While we continue to find that the mass distribution of a binary's more massive component strongly decreases as a function of primary mass, we observe no evidence of a strongly suppressed merger rate above approximately 60M⊙, which would indicate the presence of a upper mass gap. Observed black hole spins are small, with half of spin magnitudes below χi≈0.25. While the majority of spins are preferentially aligned with the orbital angular momentum, we infer evidence of antialigned spins among the binary population. We observe an increase in spin magnitude for systems with more unequal-mass ratio. We also observe evidence of misalignment of spins relative to the orbital angular momentum
The population of merging compact binaries inferred using gravitational waves through GWTC-3
We report on the population properties of 76 compact binary mergers detected with gravitational waves below a false alarm rate of 1 per year through GWTC-3. The catalog contains three classes of binary mergers: BBH, BNS, and NSBH mergers. We infer the BNS merger rate to be between 10 and 1700 and the NSBH merger rate to be between 7.8 and 140 , assuming a constant rate density versus comoving volume and taking the union of 90% credible intervals for methods used in this work. Accounting for the BBH merger rate to evolve with redshift, we find the BBH merger rate to be between 17.9 and 44 at a fiducial redshift (z=0.2). We obtain a broad neutron star mass distribution extending from to . We can confidently identify a rapid decrease in merger rate versus component mass between neutron star-like masses and black-hole-like masses, but there is no evidence that the merger rate increases again before 10 . We also find the BBH mass distribution has localized over- and under-densities relative to a power law distribution. While we continue to find the mass distribution of a binary's more massive component strongly decreases as a function of primary mass, we observe no evidence of a strongly suppressed merger rate above . The rate of BBH mergers is observed to increase with redshift at a rate proportional to with for . Observed black hole spins are small, with half of spin magnitudes below . We observe evidence of negative aligned spins in the population, and an increase in spin magnitude for systems with more unequal mass ratio
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