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2. Current status and new avenues of stem cell-based preclinical and therapeutic approaches in amyotrophic lateral sclerosis

Author

Mazzini, L, De Marchi, F, Buzanska, L, Follenzi, A, Glover, J, Gelati, M, Lombardi, I, Maioli, M, Mesa-Herrera, F, Mitrečić, D, Olgasi, C, Pivoriūnas, A, Sanchez-Pernaute, R, Sgromo, C, Zychowicz, M, Vescovi, A, Ferrari, D, Mazzini L., De Marchi F., Buzanska L., Follenzi A., Glover J. C., Gelati M., Lombardi I., Maioli M., Mesa-Herrera F., Mitrečić D., Olgasi C., Pivoriūnas A., Sanchez-Pernaute R., Sgromo C., Zychowicz M., Vescovi A., Ferrari D., Mazzini, L, De Marchi, F, Buzanska, L, Follenzi, A, Glover, J, Gelati, M, Lombardi, I, Maioli, M, Mesa-Herrera, F, Mitrečić, D, Olgasi, C, Pivoriūnas, A, Sanchez-Pernaute, R, Sgromo, C, Zychowicz, M, Vescovi, A, Ferrari, D, Mazzini L., De Marchi F., Buzanska L., Follenzi A., Glover J. C., Gelati M., Lombardi I., Maioli M., Mesa-Herrera F., Mitrečić D., Olgasi C., Pivoriūnas A., Sanchez-Pernaute R., Sgromo C., Zychowicz M., Vescovi A., and Ferrari D.

Abstract

Introduction: Cell therapy development represents a critical challenge in amyotrophic lateral sclerosis (ALS) research. Despite more than 20 years of basic and clinical research, no definitive safety and efficacy results of cell-based therapies for ALS have been published. Areas covered: This review summarizes advances using stem cells (SCs) in pre-clinical studies to promote clinical translation and in clinical trials to treat ALS. New technologies have been developed and new experimental in vitro and animal models are now available to facilitate pre-clinical research in this field and to determine the most promising approaches to pursue in patients. New clinical trial designs aimed at developing personalized SC-based treatment with biological endpoints are being defined. Expert opinion: Knowledge of the basic biology of ALS and on the use of SCs to study and potentially treat ALS continues to grow. However, a consensus has yet to emerge on how best to translate these results into therapeutic applications. The selection and follow-up of patients should be based on clinical, biological, and molecular criteria. Planning of SC-based clinical trials should be coordinated with patient profiling genetically and molecularly to achieve personalized treatment. Much work within basic and clinical research is still needed to successfully transition SC therapy in ALS.

Published
2024

3. Dietary ratio of linoleic to alpha-linolenic acid affects the reproductive performance of Japanese quail.

Author

Silva, L. A. L. da, Euzébio Dornelas, T. C., De Marchi, F. E., and dos Santos, T. C.

Subjects
JAPANESE quail, LINOLEIC acid, ALPHA-linolenic acid, LINSEED oil, SOY oil, EGG yolk
Abstract

1. This study was conducted to assess the effects of different dietary omega 6:3 ratios fed to male and female Japanese quail breeders on incubation performance, chick quality and progeny performance. 2. A completely randomised design was used, with five diets containing different ratios of vegetable oils rich in linoleic acid (LA from soybean oil) or α-linolenic acid (ALA from linseed oil) with LA/ALA ratios of 13.75:1, 10.69:1, 7.63:1, 4.57:1 and 1.48:1 with 12 cage replicates containing six birds each. 3. There was a quadratic effect of the LA/ALA ratio on total hatchability (p < 0.011), fertile hatchability (p = 0.046) and total mortality (p = 0.046). There was no effect on fertility (p > 0.05). The LA/ALA ratios of 1.48 and 13.75 fed to both hens and cockerels or hens resulted in greater fertility, as measured by the number of days after copulation during which fertile eggs were laid and the number of points of hydrolysis on the perivitelline membrane. A decreasing linear effect (p < 0.0001) was observed on chick length and an increasing linear effect on body weight at 1 day of age. There were no effects on progeny performance. 4. The LA/ALA ratio affected yolk mineral matter (p = 0.009), crude protein (p = 0.091), chick mineral matter (p < 0.038) and ether extract (p < 0.0001) contents. Maternal diet affected the fatty acid profile of egg yolk and chick liver, indicating that dietary contents were transferred to eggs and chicks. 5. Fertile egg production increased with lower LA/ALA ratios. Therefore, linseed oil can be used together with soybean oil to formulate diets for female Japanese quail obtain LA/ALA ratios between 4:1 and 10:1. [ABSTRACT FROM AUTHOR]

Published
2024
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7. State space modelling and data analysis exercises in LISA Pathfinder

Author

Nofrarias, M, Antonucci, F, Armano, M, Audley, H, Auger, G, Benedetti, M, Binetruy, P, Bogenstahl, J, Bortoluzzi, D, Brandt, N, Caleno, M, Cavalleri, A, Congedo, G, Cruise, M, Danzmann, K, De Marchi, F, Diaz-Aguilo, M, Diepholz, I, Dixon, G, Dolesi, R, Dunbar, N, Fauste, J, Ferraioli, L, Fichter, V Ferroni W, Fitzsimons, E, Freschi, M, Marirrodriga, C García, Gerndt, R, Gesa, L, Gibert, F, Giardini, D, Grimani, C, Grynagier, A, Guzmán, F, Harrison, I, Heinzel, G, Hewitson, M, Hollington, D, Hoyland, D, Hueller, M, Huesler, J, Jennrich, O, Jetzer, P, Johlander, B, Karnesis, N, Korsakova, N, Killow, C, Llamas, X, Lloro, I, Lobo, A, Maarschalkerweerd, R, Madden, S, Mance, D, Mateos, I, McNamara, P W, Mendes, J, Mitchell, E, Nicolini, D, Nicolodi, D, Perreur-Lloyd, M, Plagnol, E, Prat, P, Ramos-Castro, J, Reiche, J, Perez, J A Romera, Robertson, D, Rozemeijer, H, Russano, G, Schleicher, A, Shaul, D, Sopuerta, CF, Sumner, T J, Taylor, A, Texier, D, Trenkel, C, Tu, H-B, Vitale, S, Wanner, G, Ward, H, Waschke, S, Wass, P, Wealthy, D, Wen, S, Weber, W J, Ziegler, T, and Zweifel, P

Subjects
General Relativity and Quantum Cosmology, Astrophysics - Instrumentation and Methods for Astrophysics, Physics - Data Analysis, Statistics and Probability, Physics - Instrumentation and Detectors
Abstract

LISA Pathfinder is a mission planned by the European Space Agency to test the key technologies that will allow the detection of gravitational waves in space. The instrument on-board, the LISA Technology package, will undergo an exhaustive campaign of calibrations and noise characterisation campaigns in order to fully describe the noise model. Data analysis plays an important role in the mission and for that reason the data analysis team has been developing a toolbox which contains all the functionalities required during operations. In this contribution we give an overview of recent activities, focusing on the improvements in the modelling of the instrument and in the data analysis campaigns performed both with real and simulated data., Comment: Plenary talk presented at the 9th International LISA Symposium, 21-25 May 2012, Paris

Published
2013

8. An HST search for planets in the lower Main Sequence of the globular cluster NGC 6397

Author

Nascimbeni, V., Bedin, L. R., Piotto, G., De Marchi, F., and Rich, R. M.

Subjects
Astrophysics - Earth and Planetary Astrophysics, Astrophysics - Solar and Stellar Astrophysics
Abstract

Searches for planetary transits carried out in open and globular clusters have yielded to date only a handful of weak, unconfirmed candidates. These results have been interpreted either as being insignificant, or as evidence that the cluster chemical or dynamical environment inhibits the planetary formation or survival. Most campaigns were limited by small sample statistics or systematics from ground-based photometry. In this work we performed a search for transiting planets and variables in a deep stellar field of NGC 6397 imaged by HST-ACS for 126 orbits. We analyzed 5,078 light curves, including a pure sample of 2,215 cluster-member M0-M9 dwarfs. The light curves have been corrected for systematic trends and inspected with several tools. No high-significance planetary candidate is detected. We compared this null detection with the most recent results from Kepler, showing that no conclusive evidence of lower planet incidence can be drawn. However, a very small photometric jitter is measured for early-M cluster members (<~2 mmag on 98% of them), which may be worth targeting in the near future with more optimized campaigns. Twelve variable stars are reported for the first time., Comment: 10 pages, 6 figures, 1 table; accepted for publication in A&A on February 16, 2012. Typos corrected. One figure and a short final note added

Published
2012
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9. Non-linear parameter estimation for the LTP experiment: analysis of an operational exercise

Author

Congedo, G., De Marchi, F., Ferraioli, L., Hueller, M., Vitale, S., Hewitson, M., Nofrarias, M., Monsky, A., Armano, M., Grynagier, A., Diaz-Aguilo, M., Plagnol, E., and Rais, B.

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

The precursor ESA mission LISA-Pathfinder, to be flown in 2013, aims at demonstrating the feasibility of the free-fall, necessary for LISA, the upcoming space-born gravitational wave observatory. LISA Technology Package (LTP) is planned to carry out a number of experiments, whose main targets are to identify and measure the disturbances on each test-mass, in order to reach an unprecedented low-level residual force noise. To fulfill this plan, it is then necessary to correctly design, set-up and optimize the experiments to be performed on-flight and do a full system parameter estimation. Here we describe the progress on the non-linear analysis using the methods developed in the framework of the \textit{LTPDA Toolbox}, an object-oriented MATLAB Data Analysis environment: the effort is to identify the critical parameters and remove the degeneracy by properly combining the results of different experiments coming from a closed-loop system like LTP., Comment: 6 pages, 2 figures, 1 table, Proceedings of the 8th International LISA Symposium

Published
2011

10. Time domain maximum likelihood parameter estimation in LISA Pathfinder Data Analysis

Author

Congedo, G., Ferraioli, L., Hueller, M., De Marchi, F., Vitale, S., Armano, M., Hewitson, M., and Nofrarias, M.

Subjects
Physics - Data Analysis, Statistics and Probability, Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

LISA is the upcoming space-based Gravitational Wave telescope. LISA Pathfinder, to be launched in the coming years, will prove and verify the detection principle of the fundamental Doppler link of LISA on a flight hardware identical in design to that of LISA. LISA Pathfinder will collect a picture of all noise disturbances possibly affecting LISA, achieving the unprecedented pureness of geodesic motion necessary for the detection of gravitational waves. The first steps of both missions will crucially depend on a very precise calibration of the key system parameters. Moreover, robust parameters estimation is of fundamental importance in the correct assessment of the residual force noise, an essential part of the data processing for LISA. In this paper we present a maximum likelihood parameter estimation technique in time domain being devised for this calibration and show its proficiency on simulated data and validation through Monte Carlo realizations of independent noise runs. We discuss its robustness to non-standard scenarios possibly arising during the real-life mission, as well as its independence to the initial guess and non-gaussianities. Furthermore, we apply the same technique to data produced in mission-like fashion during operational exercises with a realistic simulator provided by ESA., Comment: 16 pages (two columns), 15 figures, 5 tables, submitted to Phys. Rev. D

Published
2011
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11. From laboratory experiments to LISA Pathfinder: achieving LISA geodesic motion

Author

Antonucci, F, Armano, M, Audley, H, Auger, G, Benedetti, M, Binetruy, P, Boatella, C, Bogenstahl, J, Bortoluzzi, D, Bosetti, P, Brandt, N, Caleno, M, Cavalleri, A, Cesa, M, Chmeissani, M, Ciani, G, Conchillo, A, Congedo, G, Cristofolini, I, Cruise, M, Danzmann, K, De Marchi, F, Diaz-Aguilo, M, Diepholz, I, Dixon, G, Dolesi, R, Dunbar, N, Fauste, J, Ferraioli, L, Fertin, D, Fichter, W, Fitzsimons, E, Freschi, M, Marin, A García, Marirrodriga, C García, Gerndt, R, Gesa, L, Giardini, D, Gibert, F, Grimani, C, Grynagier, A, Guillaume, B, Guzmán, F, Harrison, I, Heinzel, G, Hewitson, M, Hollington, D, Hough, J, Hoyland, D, Hueller, M, Huesler, J, Jeannin, O, Jennrich, O, Jetzer, P, Johlander, B, Killow, C, Llamas, X, Lloro, I, Lobo, A, Maarschalkerweerd, R, Madden, S, Mance, D, Mateos, I, McNamara, P W, Mendestì, J, Mitchell, E, Monsky, A, Nicolini, D, Nicolodi, D, Nofrarias, M, Pedersen, F, Perreur-Lloyd, M, Perreca, A, Plagnol, E, Prat, P, Racca, G D, Rais, B, Ramos-Castro, J, Reiche, J, Perez, J A Romera, Robertson, D, Rozemeijer, H, Sanjuan, J, Schleicher, A, Schulte, M, Shaul, D, Stagnaro, L, Strandmoe, S, Steier, F, Sumner, T J, Taylor, A, Texier, D, Trenkel, C, Tombolato, D, Vitale, S, Wanner, G, Ward, H, Waschke, S, Wass, P, Weber, W J, and Zweifel, P

Subjects
General Relativity and Quantum Cosmology, Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

This paper presents a quantitative assessment of the performance of the upcoming LISA Pathfinder geodesic explorer mission. The findings are based on the results of extensive ground testing and simulation campaigns using flight hardware and flight control and operations algorithms. The results show that, for the central experiment of measuring the stray differential acceleration between the LISA test masses, LISA Pathfinder will be able to verify the overall acceleration noise to within a factor two of the LISA requirement at 1 mHz and within a factor 6 at 0.1 mHz. We also discuss the key elements of the physical model of disturbances, coming from LISA Pathfinder and ground measurement, that will guarantee the LISA performance., Comment: Proceedings of the 8th LISA Symposium. To appear Class. Quantum Grav. 28 (2011)

Published
2010
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12. Modulation of LISA free-fall orbits due to the Earth-Moon system

Author

Cerdonio, M., De Marchi, F., De Pietri, R., Jetzer, P., Marzari, F., Mazzolo, G., Ortolan, A., and Sereno, M.

Subjects
General Relativity and Quantum Cosmology
Abstract

We calculate the effect of the Earth-Moon (EM) system on the free-fall motion of LISA test masses. We show that the periodic gravitational pulling of the EM system induces a resonance with fundamental frequency 1 yr^-1 and a series of periodic perturbations with frequencies equal to integer harmonics of the synodic month (9.92 10^-7 Hz). We then evaluate the effects of these perturbations (up to the 6th harmonics) on the relative motions between each test masses couple, finding that they range between 3mm and 10pm for the 2nd and 6th harmonic, respectively. If we take the LISA sensitivity curve, as extrapolated down to 10^-6 Hz, we obtain that a few harmonics of the EM system can be detected in the Doppler data collected by the LISA space mission. This suggests that the EM system gravitational near field could provide an absolute calibration for the LISA sensitivity at very low frequencies., Comment: 15 pages, 5 figures

Published
2010
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13. BVRIJHK photometry and proper motion analysis of NGC 6253 and the surrounding field

Author

Montalto, M., Piotto, G., Desidera, S., Platais, I., Carraro, G., Momany, Y., De Marchi, F., and Recio-Blanco, A.

Subjects
Astrophysics - Astrophysics of Galaxies
Abstract

Context. We present a photometric and astrometric catalog of 187963 stars located in the field around the old super-metal-rich Galactic open cluster NGC 6253. The total field-of-view covered by the catalog is 34' x 33'. In this field, we provide CCD BVRI photometry. For a smaller region close to the cluster's center, we also provide near-infrared JHK photometry. Aims. We analyze the properties of NGC 6253 by using our new photometric data and astrometric membership. Methods. In June 2004, we targeted the cluster during a 10 day multi-site campaign, which involved the MPG/ESO 2.2m telescope with its wide-field imager and the Anglo-Australian 3.9m telescope, equipped with the IRIS2 near-infrared imager. Archival CCD images of NGC 6253 were used to derive relative proper motions and to calculate the cluster membership probabilities. Results. We have refined the cluster's fundamental parameters, deriving (V_0-M_v)=11.15, E(B - V)=0.15, E(V - I)=0.25, E(V - J)=0.50, and E(V - H)=0.55. The color excess ratios obtained using both the optical and near infrared colors indicate a normal reddening law in the direction of NGC 6253. The age of NGC 6253 at 3.5 Gyr, determined from our best-fitting isochrone appears to be slightly older than the previous estimates. Finally, we estimated the binary fraction among the cluster members to be \sim20%-30% and identified 11 blue straggler candidates., Comment: 16 pages, 13 figures, 11 tables. Accepted for publication in A&A. Catalog avaiable via CDS

Published
2009
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14. Variable stars in the open cluster NGC 6791 and its surrounding field

Author

De Marchi, F., Poretti, E., Montalto, M., Piotto, G., Desidera, S., Bedin, L. R., Claudi, R., Ferro, A. Arellano, Bruntt, H., and Stetson, P. B.

Subjects
Astrophysics
Abstract

Aims: This work presents a high--precision variability survey in the field of the old, super metal-rich open cluster NGC 6791. Methods: The data sample consists of more than 75,000 high-precision CCD time series measurements in the V band obtained mainly at the Canada-France-Hawaii Telescope, with additional data from S. Pedro Martir and Loiano observatories, over a time span of ten nights. The field covers an area of 42x28 arcmin^2. Results: We have discovered 260 new variables and re-determined periods and amplitudes of 70 known variable stars. By means of a photometric evaluation of the membership in NGC 6791, and a preliminary membership based on the proper motions, we give a full description of the variable content of the cluster and surrounding field in the range 16

Published
2007
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15. A new search for planet transits in NGC 6791

Author

Montalto, M., Piotto, G., Desidera, S., De Marchi, F., Bruntt, H., Stetson, P. B., Ferro, A. Arellano, Momany, Y., Gratton, R. G., Poretti, E., Aparicio, A., Barbieri, M., Claudi, R. U., Grundahl, G., and Rosenberg, A.

Subjects
Astrophysics
Abstract

Context. Searching for planets in open clusters allows us to study the effects of dynamical environment on planet formation and evolution. Aims. Considering the strong dependence of planet frequency on stellar metallicity, we studied the metal rich old open cluster NGC 6791 and searched for close-in planets using the transit technique. Methods. A ten-night observational campaign was performed using the Canada-France-Hawaii Telescope (3.6m), the San Pedro M\'artir telescope (2.1m), and the Loiano telescope (1.5m). To increase the transit detection probability we also made use of the Bruntt et al. (2003) eight-nights observational campaign. Adequate photometric precision for the detection of planetary transits was achieved. Results. Should the frequency and properties of close-in planets in NGC 6791 be similar to those orbiting field stars of similar metallicity, then detailed simulations foresee the presence of 2-3 transiting planets. Instead, we do not confirm the transit candidates proposed by Bruntt et al. (2003). The probability that the null detection is simply due to chance coincidence is estimated to be 3%-10%, depending on the metallicity assumed for the cluster. Conclusions. Possible explanations of the null-detection of transits include: (i) a lower frequency of close-in planets in star clusters; (ii) a smaller planetary radius for planets orbiting super metal rich stars; or (iii) limitations in the basic assumptions. More extensive photometry with 3-4m class telescopes is required to allow conclusive inferences about the frequency of planets in NGC 6791., Comment: 23 pages, 23 figures, A&A accepted

Published
2007
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16. Search and analysis of blue straggler stars in open clusters

Author

De Marchi, F., De Angeli, F., Piotto, G., Carraro, G., and Davies, M. B.

Subjects
Astrophysics
Abstract

Aims: This paper presents a new homogeneous catalogue of blue straggler stars (BSS) in Galactic open clusters. Methods: Photometric data for 216 clusters were collected from the literature and 2782 BSS candidates were extracted from 76 of them. Results: We found that the anticorrelation of BSS frequency vs. total magnitude identified in similar studies conducted on Galactic globular clusters extends to the open cluster regime: clusters with smaller total magnitude tend to have higher BSS frequencies. Moreover, a clear correlation between the BSS frequency (obtained normalising the total number of BSS either to the total cluster mass or, for the older clusters, to the total number of clump stars) and the age of the clusters was found. A simple model is developed here to try to explain this last and new result. The model allows us to ascertain the important effect played by mass loss in the evolution of open clusters.

Published
2006
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18. Gravity, Geodesy and Fundamental Physics with BepiColombo’s MORE Investigation

Author

Iess, L., Asmar, S. W., Cappuccio, P., Cascioli, G., De Marchi, F., di Stefano, I., Genova, A., Ashby, N., Barriot, J. P., Bender, P., Benedetto, C., Border, J. S., Budnik, F., Ciarcia, S., Damour, T., Dehant, V., Di Achille, G., Di Ruscio, A., Fienga, A., Formaro, R., Klioner, S., Konopliv, A., Lemaître, A., Longo, F., Mercolino, M., Mitri, G., Notaro, V., Olivieri, A., Paik, M., Palli, A., Schettino, G., Serra, D., Simone, L., Tommei, G., Tortora, P., Van Hoolst, T., Vokrouhlický, D., Watkins, M., Wu, X., and Zannoni, M.

Published
2021
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19. Author Correction: Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology (Nature Genetics, (2021), 53, 12, (1636-1648), 10.1038/s41588-021-00973-1)

Author

van Rheenen W., van Rheenen, W, van der Spek, R, Bakker, M, van Vugt, J, Hop, P, Zwamborn, R, de Klein, N, Westra, H, Bakker, O, Deelen, P, Shireby, G, Hannon, E, Moisse, M, Baird, D, Restuadi, R, Dolzhenko, E, Dekker, A, Gawor, K, Westeneng, H, Tazelaar, G, van Eijk, K, Kooyman, M, Byrne, R, Doherty, M, Heverin, M, Al Khleifat, A, Iacoangeli, A, Shatunov, A, Ticozzi, N, Cooper-Knock, J, Smith, B, Gromicho, M, Chandran, S, Pal, S, Morrison, K, Shaw, P, Hardy, J, Orrell, R, Sendtner, M, Meyer, T, Basak, N, van der Kooi, A, Ratti, A, Fogh, I, Gellera, C, Lauria, G, Corti, S, Cereda, C, Sproviero, D, D'Alfonso, S, Soraru, G, Siciliano, G, Filosto, M, Padovani, A, Chio, A, Calvo, A, Moglia, C, Brunetti, M, Canosa, A, Grassano, M, Beghi, E, Pupillo, E, Logroscino, G, Nefussy, B, Osmanovic, A, Nordin, A, Lerner, Y, Zabari, M, Gotkine, M, Baloh, R, Bell, S, Vourc'H, P, Corcia, P, Couratier, P, Millecamps, S, Meininger, V, Salachas, F, Mora Pardina, J, Assialioui, A, Rojas-Garcia, R, Dion, P, Ross, J, Ludolph, A, Weishaupt, J, Brenner, D, Freischmidt, A, Bensimon, G, Brice, A, Durr, A, Payan, C, Saker-Delye, S, Wood, N, Topp, S, Rademakers, R, Tittmann, L, Lieb, W, Franke, A, Ripke, S, Braun, A, Kraft, J, Whiteman, D, Olsen, C, Uitterlinden, A, Hofman, A, Rietschel, M, Cichon, S, Nothen, M, Amouyel, P, Comi, G, Riva, N, Lunetta, C, Gerardi, F, Cotelli, M, Rinaldi, F, Chiveri, L, Guaita, M, Perrone, P, Ceroni, M, Diamanti, L, Ferrarese, C, Tremolizzo, L, Delodovici, M, Bono, G, Manera, U, Vasta, R, Bombaci, A, Casale, F, Fuda, G, Salamone, P, Iazzolino, B, Peotta, L, Cugnasco, P, De Marco, G, Torrieri, M, Palumbo, F, Gallone, S, Barberis, M, Sbaiz, L, Gentile, S, Mauro, A, Mazzini, L, De Marchi, F, Corrado, L, Bertolotto, A, Gionco, M, Leotta, D, Odddenino, E, Imperiale, D, Cavallo, R, Pignatta, P, De Mattei, M, Geda, C, Papurello, D, Gusmaroli, G, Comi, C, Labate, C, Ruiz, L, Ferrandi, D, Rota, E, Aguggia, M, Di Vito, N, Meineri, P, Ghiglione, P, Launaro, N, Dotta, M, Di Sapio, A, Giardini, G, Tiloca, C, Peverelli, S, Taroni, F, Pensato, V, Castellotti, B, Del Bo, R, Gagliardi, S, Raggi, F, Simoncini, C, Lo Gerfo, A, Inghilleri, M, Ferlini, A, Simone, I, Passarella, B, Guerra, V, Zoccolella, S, Nozzoli, C, Mundi, C, Leone, M, Zarrelli, M, Tamma, F, Valluzzi, F, Calabrese, G, Boero, G, Rini, A, Traynor, B, Singleton, A, Mitne Neto, M, Cauchi, R, Ophoff, R, Wiedau-Pazos, M, Lomen-Hoerth, C, van Deerlin, V, Grosskreutz, J, Roediger, A, Gaur, N, Jork, A, Barthel, T, Theele, E, Ilse, B, Stubendorff, B, Witte, O, Steinbach, R, Hubner, C, Graff, C, Brylev, L, Fominykh, V, Demeshonok, V, Ataulina, A, Rogelj, B, Koritnik, B, Zidar, J, Ravnik-Glavac, M, Glavac, D, Stevic, Z, Drory, V, Povedano, M, Blair, I, Kiernan, M, Benyamin, B, Henderson, R, Furlong, S, Mathers, S, Mccombe, P, Needham, M, Ngo, S, Nicholson, G, Pamphlett, R, Rowe, D, Steyn, F, Williams, K, Mather, K, Sachdev, P, Henders, A, Wallace, L, de Carvalho, M, Pinto, S, Petri, S, Weber, M, Rouleau, G, Silani, V, Curtis, C, Breen, G, Glass, J, Brown, R, Landers, J, Shaw, C, Andersen, P, Groen, E, van Es, M, Pasterkamp, R, Fan, D, Garton, F, Mcrae, A, Davey Smith, G, Gaunt, T, Eberle, M, Mill, J, Mclaughlin, R, Hardiman, O, Kenna, K, Wray, N, Tsai, E, Runz, H, Franke, L, Al-Chalabi, A, Van Damme, P, van den Berg, L, Veldink, J, van Rheenen W., van der Spek R. A. A., Bakker M. K., van Vugt J. J. F. A., Hop P. J., Zwamborn R. A. J., de Klein N., Westra H. -J., Bakker O. B., Deelen P., Shireby G., Hannon E., Moisse M., Baird D., Restuadi R., Dolzhenko E., Dekker A. M., Gawor K., Westeneng H. -J., Tazelaar G. H. P., van Eijk K. R., Kooyman M., Byrne R. P., Doherty M., Heverin M., Al Khleifat A., Iacoangeli A., Shatunov A., Ticozzi N., Cooper-Knock J., Smith B. N., Gromicho M., Chandran S., Pal S., Morrison K. E., Shaw P. J., Hardy J., Orrell R. W., Sendtner M., Meyer T., Basak N., van der Kooi A. J., Ratti A., Fogh I., Gellera C., Lauria G., Corti S., Cereda C., Sproviero D., D'Alfonso S., Soraru G., Siciliano G., Filosto M., Padovani A., Chio A., Calvo A., Moglia C., Brunetti M., Canosa A., Grassano M., Beghi E., Pupillo E., Logroscino G., Nefussy B., Osmanovic A., Nordin A., Lerner Y., Zabari M., Gotkine M., Baloh R. H., Bell S., Vourc'h P., Corcia P., Couratier P., Millecamps S., Meininger V., Salachas F., Mora Pardina J. S., Assialioui A., Rojas-Garcia R., Dion P. A., Ross J. P., Ludolph A. C., Weishaupt J. H., Brenner D., Freischmidt A., Bensimon G., Brice A., Durr A., Payan C. A. M., Saker-Delye S., Wood N. W., Topp S., Rademakers R., Tittmann L., Lieb W., Franke A., Ripke S., Braun A., Kraft J., Whiteman D. C., Olsen C. M., Uitterlinden A. G., Hofman A., Rietschel M., Cichon S., Nothen M. M., Amouyel P., Comi G., Riva N., Lunetta C., Gerardi F., Cotelli M. S., Rinaldi F., Chiveri L., Guaita M. C., Perrone P., Ceroni M., Diamanti L., Ferrarese C., Tremolizzo L., Delodovici M. L., Bono G., Manera U., Vasta R., Bombaci A., Casale F., Fuda G., Salamone P., Iazzolino B., Peotta L., Cugnasco P., De Marco G., Torrieri M. C., Palumbo F., Gallone S., Barberis M., Sbaiz L., Gentile S., Mauro A., Mazzini L., De Marchi F., Corrado L., Bertolotto A., Gionco M., Leotta D., Odddenino E., Imperiale D., Cavallo R., Pignatta P., De Mattei M., Geda C., Papurello D. M., Gusmaroli G., Comi C., Labate C., Ruiz L., Ferrandi D., Rota E., Aguggia M., Di Vito N., Meineri P., Ghiglione P., Launaro N., Dotta M., Di Sapio A., Giardini G., Tiloca C., Peverelli S., Taroni F., Pensato V., Castellotti B., Comi G. P., Del Bo R., Gagliardi S., Raggi F., Simoncini C., Lo Gerfo A., Inghilleri M., Ferlini A., Simone I. L., Passarella B., Guerra V., Zoccolella S., Nozzoli C., Mundi C., Leone M., Zarrelli M., Tamma F., Valluzzi F., Calabrese G., Boero G., Rini A., Traynor B. J., Singleton A. B., Mitne Neto M., Cauchi R. J., Ophoff R. A., Wiedau-Pazos M., Lomen-Hoerth C., van Deerlin V. M., Grosskreutz J., Roediger A., Gaur N., Jork A., Barthel T., Theele E., Ilse B., Stubendorff B., Witte O. W., Steinbach R., Hubner C. A., Graff C., Brylev L., Fominykh V., Demeshonok V., Ataulina A., Rogelj B., Koritnik B., Zidar J., Ravnik-Glavac M., Glavac D., Stevic Z., Drory V., Povedano M., Blair I. P., Kiernan M. C., Benyamin B., Henderson R. D., Furlong S., Mathers S., McCombe P. A., Needham M., Ngo S. T., Nicholson G. A., Pamphlett R., Rowe D. B., Steyn F. J., Williams K. L., Mather K. A., Sachdev P. S., Henders A. K., Wallace L., de Carvalho M., Pinto S., Petri S., Weber M., Rouleau G. A., Silani V., Curtis C. J., Breen G., Glass J. D., Brown R. H., Landers J. E., Shaw C. E., Andersen P. M., Groen E. J. N., van Es M. A., Pasterkamp R. J., Fan D., Garton F. C., McRae A. F., Davey Smith G., Gaunt T. R., Eberle M. A., Mill J., McLaughlin R. L., Hardiman O., Kenna K. P., Wray N. R., Tsai E., Runz H., Franke L., Al-Chalabi A., Van Damme P., van den Berg L. H., Veldink J. H., van Rheenen W., van Rheenen, W, van der Spek, R, Bakker, M, van Vugt, J, Hop, P, Zwamborn, R, de Klein, N, Westra, H, Bakker, O, Deelen, P, Shireby, G, Hannon, E, Moisse, M, Baird, D, Restuadi, R, Dolzhenko, E, Dekker, A, Gawor, K, Westeneng, H, Tazelaar, G, van Eijk, K, Kooyman, M, Byrne, R, Doherty, M, Heverin, M, Al Khleifat, A, Iacoangeli, A, Shatunov, A, Ticozzi, N, Cooper-Knock, J, Smith, B, Gromicho, M, Chandran, S, Pal, S, Morrison, K, Shaw, P, Hardy, J, Orrell, R, Sendtner, M, Meyer, T, Basak, N, van der Kooi, A, Ratti, A, Fogh, I, Gellera, C, Lauria, G, Corti, S, Cereda, C, Sproviero, D, D'Alfonso, S, Soraru, G, Siciliano, G, Filosto, M, Padovani, A, Chio, A, Calvo, A, Moglia, C, Brunetti, M, Canosa, A, Grassano, M, Beghi, E, Pupillo, E, Logroscino, G, Nefussy, B, Osmanovic, A, Nordin, A, Lerner, Y, Zabari, M, Gotkine, M, Baloh, R, Bell, S, Vourc'H, P, Corcia, P, Couratier, P, Millecamps, S, Meininger, V, Salachas, F, Mora Pardina, J, Assialioui, A, Rojas-Garcia, R, Dion, P, Ross, J, Ludolph, A, Weishaupt, J, Brenner, D, Freischmidt, A, Bensimon, G, Brice, A, Durr, A, Payan, C, Saker-Delye, S, Wood, N, Topp, S, Rademakers, R, Tittmann, L, Lieb, W, Franke, A, Ripke, S, Braun, A, Kraft, J, Whiteman, D, Olsen, C, Uitterlinden, A, Hofman, A, Rietschel, M, Cichon, S, Nothen, M, Amouyel, P, Comi, G, Riva, N, Lunetta, C, Gerardi, F, Cotelli, M, Rinaldi, F, Chiveri, L, Guaita, M, Perrone, P, Ceroni, M, Diamanti, L, Ferrarese, C, Tremolizzo, L, Delodovici, M, Bono, G, Manera, U, Vasta, R, Bombaci, A, Casale, F, Fuda, G, Salamone, P, Iazzolino, B, Peotta, L, Cugnasco, P, De Marco, G, Torrieri, M, Palumbo, F, Gallone, S, Barberis, M, Sbaiz, L, Gentile, S, Mauro, A, Mazzini, L, De Marchi, F, Corrado, L, Bertolotto, A, Gionco, M, Leotta, D, Odddenino, E, Imperiale, D, Cavallo, R, Pignatta, P, De Mattei, M, Geda, C, Papurello, D, Gusmaroli, G, Comi, C, Labate, C, Ruiz, L, Ferrandi, D, Rota, E, Aguggia, M, Di Vito, N, Meineri, P, Ghiglione, P, Launaro, N, Dotta, M, Di Sapio, A, Giardini, G, Tiloca, C, Peverelli, S, Taroni, F, Pensato, V, Castellotti, B, Del Bo, R, Gagliardi, S, Raggi, F, Simoncini, C, Lo Gerfo, A, Inghilleri, M, Ferlini, A, Simone, I, Passarella, B, Guerra, V, Zoccolella, S, Nozzoli, C, Mundi, C, Leone, M, Zarrelli, M, Tamma, F, Valluzzi, F, Calabrese, G, Boero, G, Rini, A, Traynor, B, Singleton, A, Mitne Neto, M, Cauchi, R, Ophoff, R, Wiedau-Pazos, M, Lomen-Hoerth, C, van Deerlin, V, Grosskreutz, J, Roediger, A, Gaur, N, Jork, A, Barthel, T, Theele, E, Ilse, B, Stubendorff, B, Witte, O, Steinbach, R, Hubner, C, Graff, C, Brylev, L, Fominykh, V, Demeshonok, V, Ataulina, A, Rogelj, B, Koritnik, B, Zidar, J, Ravnik-Glavac, M, Glavac, D, Stevic, Z, Drory, V, Povedano, M, Blair, I, Kiernan, M, Benyamin, B, Henderson, R, Furlong, S, Mathers, S, Mccombe, P, Needham, M, Ngo, S, Nicholson, G, Pamphlett, R, Rowe, D, Steyn, F, Williams, K, Mather, K, Sachdev, P, Henders, A, Wallace, L, de Carvalho, M, Pinto, S, Petri, S, Weber, M, Rouleau, G, Silani, V, Curtis, C, Breen, G, Glass, J, Brown, R, Landers, J, Shaw, C, Andersen, P, Groen, E, van Es, M, Pasterkamp, R, Fan, D, Garton, F, Mcrae, A, Davey Smith, G, Gaunt, T, Eberle, M, Mill, J, Mclaughlin, R, Hardiman, O, Kenna, K, Wray, N, Tsai, E, Runz, H, Franke, L, Al-Chalabi, A, Van Damme, P, van den Berg, L, Veldink, J, van Rheenen W., van der Spek R. A. A., Bakker M. K., van Vugt J. J. F. A., Hop P. J., Zwamborn R. A. J., de Klein N., Westra H. -J., Bakker O. B., Deelen P., Shireby G., Hannon E., Moisse M., Baird D., Restuadi R., Dolzhenko E., Dekker A. M., Gawor K., Westeneng H. -J., Tazelaar G. H. P., van Eijk K. R., Kooyman M., Byrne R. P., Doherty M., Heverin M., Al Khleifat A., Iacoangeli A., Shatunov A., Ticozzi N., Cooper-Knock J., Smith B. N., Gromicho M., Chandran S., Pal S., Morrison K. E., Shaw P. J., Hardy J., Orrell R. W., Sendtner M., Meyer T., Basak N., van der Kooi A. J., Ratti A., Fogh I., Gellera C., Lauria G., Corti S., Cereda C., Sproviero D., D'Alfonso S., Soraru G., Siciliano G., Filosto M., Padovani A., Chio A., Calvo A., Moglia C., Brunetti M., Canosa A., Grassano M., Beghi E., Pupillo E., Logroscino G., Nefussy B., Osmanovic A., Nordin A., Lerner Y., Zabari M., Gotkine M., Baloh R. H., Bell S., Vourc'h P., Corcia P., Couratier P., Millecamps S., Meininger V., Salachas F., Mora Pardina J. S., Assialioui A., Rojas-Garcia R., Dion P. A., Ross J. P., Ludolph A. C., Weishaupt J. H., Brenner D., Freischmidt A., Bensimon G., Brice A., Durr A., Payan C. A. M., Saker-Delye S., Wood N. W., Topp S., Rademakers R., Tittmann L., Lieb W., Franke A., Ripke S., Braun A., Kraft J., Whiteman D. C., Olsen C. M., Uitterlinden A. G., Hofman A., Rietschel M., Cichon S., Nothen M. M., Amouyel P., Comi G., Riva N., Lunetta C., Gerardi F., Cotelli M. S., Rinaldi F., Chiveri L., Guaita M. C., Perrone P., Ceroni M., Diamanti L., Ferrarese C., Tremolizzo L., Delodovici M. L., Bono G., Manera U., Vasta R., Bombaci A., Casale F., Fuda G., Salamone P., Iazzolino B., Peotta L., Cugnasco P., De Marco G., Torrieri M. C., Palumbo F., Gallone S., Barberis M., Sbaiz L., Gentile S., Mauro A., Mazzini L., De Marchi F., Corrado L., Bertolotto A., Gionco M., Leotta D., Odddenino E., Imperiale D., Cavallo R., Pignatta P., De Mattei M., Geda C., Papurello D. M., Gusmaroli G., Comi C., Labate C., Ruiz L., Ferrandi D., Rota E., Aguggia M., Di Vito N., Meineri P., Ghiglione P., Launaro N., Dotta M., Di Sapio A., Giardini G., Tiloca C., Peverelli S., Taroni F., Pensato V., Castellotti B., Comi G. P., Del Bo R., Gagliardi S., Raggi F., Simoncini C., Lo Gerfo A., Inghilleri M., Ferlini A., Simone I. L., Passarella B., Guerra V., Zoccolella S., Nozzoli C., Mundi C., Leone M., Zarrelli M., Tamma F., Valluzzi F., Calabrese G., Boero G., Rini A., Traynor B. J., Singleton A. B., Mitne Neto M., Cauchi R. J., Ophoff R. A., Wiedau-Pazos M., Lomen-Hoerth C., van Deerlin V. M., Grosskreutz J., Roediger A., Gaur N., Jork A., Barthel T., Theele E., Ilse B., Stubendorff B., Witte O. W., Steinbach R., Hubner C. A., Graff C., Brylev L., Fominykh V., Demeshonok V., Ataulina A., Rogelj B., Koritnik B., Zidar J., Ravnik-Glavac M., Glavac D., Stevic Z., Drory V., Povedano M., Blair I. P., Kiernan M. C., Benyamin B., Henderson R. D., Furlong S., Mathers S., McCombe P. A., Needham M., Ngo S. T., Nicholson G. A., Pamphlett R., Rowe D. B., Steyn F. J., Williams K. L., Mather K. A., Sachdev P. S., Henders A. K., Wallace L., de Carvalho M., Pinto S., Petri S., Weber M., Rouleau G. A., Silani V., Curtis C. J., Breen G., Glass J. D., Brown R. H., Landers J. E., Shaw C. E., Andersen P. M., Groen E. J. N., van Es M. A., Pasterkamp R. J., Fan D., Garton F. C., McRae A. F., Davey Smith G., Gaunt T. R., Eberle M. A., Mill J., McLaughlin R. L., Hardiman O., Kenna K. P., Wray N. R., Tsai E., Runz H., Franke L., Al-Chalabi A., Van Damme P., van den Berg L. H., and Veldink J. H.

Abstract

In the version of this article initially published, the affiliation for Nazli Başak appeared incorrectly. Nazli Başak is at Koç University, School of Medicine, KUTTAM-NDAL, Istanbul, Turkey, and not Bogazici University. The error has been corrected in the HTML and PDF versions of the article.

Published
2022

22. Generation of an induced pluripotent stem cell line, CSSi011-A (6534), from an Amyotrophic lateral sclerosis patient with heterozygous L145F mutation in SOD1 gene

Author

D'Anzi, A, Altieri, F, Perciballi, E, Ferrari, D, Bernardini, L, Goldoni, M, Mazzini, L, De Marchi, F, Di Pierro, A, D'Alfonso, S, Gelati, M, Vescovi, A, Rosati, J, D'Anzi A., Altieri F., Perciballi E., Ferrari D., Bernardini L., Goldoni M., Mazzini L., De Marchi F., Di Pierro A., D'Alfonso S., Gelati M., Vescovi A. L., Rosati J., D'Anzi, A, Altieri, F, Perciballi, E, Ferrari, D, Bernardini, L, Goldoni, M, Mazzini, L, De Marchi, F, Di Pierro, A, D'Alfonso, S, Gelati, M, Vescovi, A, Rosati, J, D'Anzi A., Altieri F., Perciballi E., Ferrari D., Bernardini L., Goldoni M., Mazzini L., De Marchi F., Di Pierro A., D'Alfonso S., Gelati M., Vescovi A. L., and Rosati J.

Abstract

Among the known causative genes of familial ALS, SOD1 mutation is one of the most common. It encodes for the ubiquitous detoxifying copper/zinc binding SOD1 enzyme, whose mutations selectively cause motor neuron death, although the mechanisms are not as yet clear. What is known is that mutant-mediated toxicity is not caused by loss of its detoxifying activity but by a gain-of-function. In order to better understand the pathogenic mechanisms of SOD1 mutation, a human induced pluripotent stem cell (hiPSC) line was generated from the somatic cells of a female patient carrying a missense variation in SOD1 (L145F).

Published
2020

23. Author Correction: Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author

van Rheenen, W., van der Spek, R.A.A., Bakker, M.K., van Vugt, J.J.F.A., Hop, P.J., Zwamborn, R.A.J., de Klein, N., Westra, H-J, Bakker, O.B., Deelen, P., Shireby, G., Hannon, E., Moisse, M., Baird, D., Restuadi, R., Dolzhenko, E., Dekker, A.M., Gawor, K., Westeneng, H-J, Tazelaar, G.H.P., van Eijk, K.R., Kooyman, M., Byrne, R.P., Doherty, M., Heverin, M., Al Khleifat, A., Iacoangeli, A., Shatunov, A., Ticozzi, N., Cooper-Knock, J., Smith, B.N., Gromicho, M., Chandran, S., Pal, S., Morrison, K.E., Shaw, P.J., Hardy, J., Orrell, R.W., Sendtner, M., Meyer, T., Başak, N., van der Kooi, A.J., Ratti, A., Fogh, I., Gellera, C., Lauria, G., Corti, S., Cereda, C., Sproviero, D., D’alfonso, S., Sorarù, G., Siciliano, G., Filosto, M., Padovani, A., Chiò, A., Calvo, A., Moglia, C., Brunetti, M., Canosa, A., Grassano, M., Beghi, E., Pupillo, E., Logroscino, G., Nefussy, B., Osmanovic, A., Nordin, A., Lerner, Y., Zabari, M., Gotkine, M., Baloh, R.H., Bell, S., Vourc’h, P., Corcia, P., Couratier, P., Millecamps, S., Meininger, V., Salachas, F., Mora Pardina, J.S., Assialioui, A., Rojas-García, R., Dion, P.A., Ross, J.P., Ludolph, A.C., Weishaupt, J.H., Brenner, D., Freischmidt, A., Bensimon, G., Brice, A., Durr, A., Payan, C.A.M., Saker-Delye, S., Wood, N.W., Topp, S., Rademakers, R., Tittmann, L., Lieb, W., Franke, A., Ripke, S., Braun, A., Kraft, J., Whiteman, D.C., Olsen, C.M., Uitterlinden, A.G., Hofman, A., Rietschel, M., Cichon, S., Nöthen, M.M., Amouyel, P., Comi, G., Riva, N., Lunetta, C., Gerardi, F., Cotelli, M.S., Rinaldi, F., Chiveri, L., Guaita, M.C., Perrone, P., Ceroni, M., Diamanti, L., Ferrarese, C., Tremolizzo, L., Delodovici, M.L., Bono, G., Manera, U., Vasta, R., Bombaci, A., Casale, F., Fuda, G., Salamone, P., Iazzolino, B., Peotta, L., Cugnasco, P., De Marco, G., Torrieri, M.C., Palumbo, F., Gallone, S., Barberis, M., Sbaiz, L., Gentile, S., Mauro, A., Mazzini, L., De Marchi, F., Corrado, L., D’Alfonso, S., Bertolotto, A., Gionco, M., Leotta, D., Odddenino, E., Imperiale, D., Cavallo, R., Pignatta, P., De Mattei, M., Geda, C., Papurello, D.M., Gusmaroli, G., Comi, C., Labate, C., Ruiz, L., Ferrandi, D., Rota, E., Aguggia, M., Di Vito, N., Meineri, P., Ghiglione, P., Launaro, N., Dotta, M., Di Sapio, A., Giardini, G., Tiloca, C., Peverelli, S., Taroni, F., Pensato, V., Castellotti, B., Comi, G.P., Del Bo, R., Gagliardi, S., Raggi, F., Simoncini, C., Lo Gerfo, A., Inghilleri, M., Ferlini, A., Simone, I.L., Passarella, B., Guerra, V., Zoccolella, S., Nozzoli, C., Mundi, C., Leone, M., Zarrelli, M., Tamma, F., Valluzzi, F., Calabrese, G., Boero, G., Rini, A., Traynor, B.J., Singleton, A.B., Mitne Neto, M., Cauchi, R.J., Ophoff, R.A., Wiedau-Pazos, M., Lomen-Hoerth, C., van Deerlin, V.M., Grosskreutz, J., Roediger, A., Gaur, N., Jörk, A., Barthel, T., Theele, E., Ilse, B., Stubendorff, B., Witte, O.W., Steinbach, R., Hübner, C.A., Graff, C., Brylev, L., Fominykh, V., Demeshonok, V., Ataulina, A., Rogelj, B., Koritnik, B., Zidar, J., Ravnik-Glavač, M., Glavač, D., Stević, Z., Drory, V., Povedano, M., Blair, I.P., Kiernan, M.C., Benyamin, B., Henderson, R.D., Furlong, S., Mathers, S., McCombe, P.A., Needham, M., Ngo, S.T., Nicholson, G.A., Pamphlett, R., Rowe, D.B., Steyn, F.J., Williams, K.L., Mather, K.A., Sachdev, P.S., Henders, A.K., Wallace, L., de Carvalho, M., Pinto, S., Petri, S., Weber, M., Rouleau, G.A., Silani, V., Curtis, C.J., Breen, G., Glass, J.D., Brown, R.H., Landers, J.E., Shaw, C.E., Andersen, P.M., Groen, E.J.N., van Es, M.A., Pasterkamp, R.J., Fan, D., Garton, F.C., McRae, A.F., Davey Smith, G., Gaunt, T.R., Eberle, M.A., Mill, J., McLaughlin, R.L., Hardiman, O., Kenna, K.P., Wray, N.R., Tsai, E., Runz, H., Franke, L., Al-Chalabi, A., Van Damme, P., van den Berg, L.H., Veldink, J.H., van Rheenen, W., van der Spek, R.A.A., Bakker, M.K., van Vugt, J.J.F.A., Hop, P.J., Zwamborn, R.A.J., de Klein, N., Westra, H-J, Bakker, O.B., Deelen, P., Shireby, G., Hannon, E., Moisse, M., Baird, D., Restuadi, R., Dolzhenko, E., Dekker, A.M., Gawor, K., Westeneng, H-J, Tazelaar, G.H.P., van Eijk, K.R., Kooyman, M., Byrne, R.P., Doherty, M., Heverin, M., Al Khleifat, A., Iacoangeli, A., Shatunov, A., Ticozzi, N., Cooper-Knock, J., Smith, B.N., Gromicho, M., Chandran, S., Pal, S., Morrison, K.E., Shaw, P.J., Hardy, J., Orrell, R.W., Sendtner, M., Meyer, T., Başak, N., van der Kooi, A.J., Ratti, A., Fogh, I., Gellera, C., Lauria, G., Corti, S., Cereda, C., Sproviero, D., D’alfonso, S., Sorarù, G., Siciliano, G., Filosto, M., Padovani, A., Chiò, A., Calvo, A., Moglia, C., Brunetti, M., Canosa, A., Grassano, M., Beghi, E., Pupillo, E., Logroscino, G., Nefussy, B., Osmanovic, A., Nordin, A., Lerner, Y., Zabari, M., Gotkine, M., Baloh, R.H., Bell, S., Vourc’h, P., Corcia, P., Couratier, P., Millecamps, S., Meininger, V., Salachas, F., Mora Pardina, J.S., Assialioui, A., Rojas-García, R., Dion, P.A., Ross, J.P., Ludolph, A.C., Weishaupt, J.H., Brenner, D., Freischmidt, A., Bensimon, G., Brice, A., Durr, A., Payan, C.A.M., Saker-Delye, S., Wood, N.W., Topp, S., Rademakers, R., Tittmann, L., Lieb, W., Franke, A., Ripke, S., Braun, A., Kraft, J., Whiteman, D.C., Olsen, C.M., Uitterlinden, A.G., Hofman, A., Rietschel, M., Cichon, S., Nöthen, M.M., Amouyel, P., Comi, G., Riva, N., Lunetta, C., Gerardi, F., Cotelli, M.S., Rinaldi, F., Chiveri, L., Guaita, M.C., Perrone, P., Ceroni, M., Diamanti, L., Ferrarese, C., Tremolizzo, L., Delodovici, M.L., Bono, G., Manera, U., Vasta, R., Bombaci, A., Casale, F., Fuda, G., Salamone, P., Iazzolino, B., Peotta, L., Cugnasco, P., De Marco, G., Torrieri, M.C., Palumbo, F., Gallone, S., Barberis, M., Sbaiz, L., Gentile, S., Mauro, A., Mazzini, L., De Marchi, F., Corrado, L., D’Alfonso, S., Bertolotto, A., Gionco, M., Leotta, D., Odddenino, E., Imperiale, D., Cavallo, R., Pignatta, P., De Mattei, M., Geda, C., Papurello, D.M., Gusmaroli, G., Comi, C., Labate, C., Ruiz, L., Ferrandi, D., Rota, E., Aguggia, M., Di Vito, N., Meineri, P., Ghiglione, P., Launaro, N., Dotta, M., Di Sapio, A., Giardini, G., Tiloca, C., Peverelli, S., Taroni, F., Pensato, V., Castellotti, B., Comi, G.P., Del Bo, R., Gagliardi, S., Raggi, F., Simoncini, C., Lo Gerfo, A., Inghilleri, M., Ferlini, A., Simone, I.L., Passarella, B., Guerra, V., Zoccolella, S., Nozzoli, C., Mundi, C., Leone, M., Zarrelli, M., Tamma, F., Valluzzi, F., Calabrese, G., Boero, G., Rini, A., Traynor, B.J., Singleton, A.B., Mitne Neto, M., Cauchi, R.J., Ophoff, R.A., Wiedau-Pazos, M., Lomen-Hoerth, C., van Deerlin, V.M., Grosskreutz, J., Roediger, A., Gaur, N., Jörk, A., Barthel, T., Theele, E., Ilse, B., Stubendorff, B., Witte, O.W., Steinbach, R., Hübner, C.A., Graff, C., Brylev, L., Fominykh, V., Demeshonok, V., Ataulina, A., Rogelj, B., Koritnik, B., Zidar, J., Ravnik-Glavač, M., Glavač, D., Stević, Z., Drory, V., Povedano, M., Blair, I.P., Kiernan, M.C., Benyamin, B., Henderson, R.D., Furlong, S., Mathers, S., McCombe, P.A., Needham, M., Ngo, S.T., Nicholson, G.A., Pamphlett, R., Rowe, D.B., Steyn, F.J., Williams, K.L., Mather, K.A., Sachdev, P.S., Henders, A.K., Wallace, L., de Carvalho, M., Pinto, S., Petri, S., Weber, M., Rouleau, G.A., Silani, V., Curtis, C.J., Breen, G., Glass, J.D., Brown, R.H., Landers, J.E., Shaw, C.E., Andersen, P.M., Groen, E.J.N., van Es, M.A., Pasterkamp, R.J., Fan, D., Garton, F.C., McRae, A.F., Davey Smith, G., Gaunt, T.R., Eberle, M.A., Mill, J., McLaughlin, R.L., Hardiman, O., Kenna, K.P., Wray, N.R., Tsai, E., Runz, H., Franke, L., Al-Chalabi, A., Van Damme, P., van den Berg, L.H., and Veldink, J.H.

Abstract

Correction to: Nature Genetics https://doi.org/10.1038/s41588-021-00973-1, published online 6 December 2021. In the version of this article initially published, the affiliation for Nazli Başak appeared incorrectly. Nazli Başak is at Koç University, School of Medicine, KUTTAM-NDAL, Istanbul, Turkey, and not Bogazici University. The error has been corrected in the HTML and PDF versions of the article.

Published
2022

24. Characterization of the p.L145F and p.S135N Mutations in SOD1: Impact on the Metabolism of Fibroblasts Derived from Amyotrophic Lateral Sclerosis Patients

Author

Perciballi, E, Bovio, F, Rosati, J, Arrigoni, F, D'Anzi, A, Lattante, S, Gelati, M, De Marchi, F, Lombardi, I, Ruotolo, G, Forcella, M, Mazzini, L, D'Alfonso, S, Corrado, L, Sabatelli, M, Conte, A, De Gioia, L, Martino, S, Vescovi, A, Fusi, P, Ferrari, D, Perciballi, Elisa, Bovio, Federica, Rosati, Jessica, Arrigoni, Federica, D'Anzi, Angela, Lattante, Serena, Gelati, Maurizio, De Marchi, Fabiola, Lombardi, Ivan, Ruotolo, Giorgia, Forcella, Matilde, Mazzini, Letizia, D'Alfonso, Sandra, Corrado, Lucia, Sabatelli, Mario, Conte, Amelia, De Gioia, Luca, Martino, Sabata, Vescovi, Angelo Luigi, Fusi, Paola, Ferrari, Daniela, Perciballi, E, Bovio, F, Rosati, J, Arrigoni, F, D'Anzi, A, Lattante, S, Gelati, M, De Marchi, F, Lombardi, I, Ruotolo, G, Forcella, M, Mazzini, L, D'Alfonso, S, Corrado, L, Sabatelli, M, Conte, A, De Gioia, L, Martino, S, Vescovi, A, Fusi, P, Ferrari, D, Perciballi, Elisa, Bovio, Federica, Rosati, Jessica, Arrigoni, Federica, D'Anzi, Angela, Lattante, Serena, Gelati, Maurizio, De Marchi, Fabiola, Lombardi, Ivan, Ruotolo, Giorgia, Forcella, Matilde, Mazzini, Letizia, D'Alfonso, Sandra, Corrado, Lucia, Sabatelli, Mario, Conte, Amelia, De Gioia, Luca, Martino, Sabata, Vescovi, Angelo Luigi, Fusi, Paola, and Ferrari, Daniela

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of the upper and lower motor neurons (MNs). About 10% of patients have a family history (familial, fALS); however, most patients seem to develop the sporadic form of the disease (sALS). SOD1 (Cu/Zn superoxide dismutase-1) is the first studied gene among the ones related to ALS. Mutant SOD1 can adopt multiple misfolded conformation, lose the correct coordination of metal binding, decrease structural stability, and form aggregates. For all these reasons, it is complicated to characterize the conformational alterations of the ALS-associated mutant SOD1, and how they relate to toxicity. In this work, we performed a multilayered study on fibroblasts derived from two ALS patients, namely SOD1L145F and SOD1S135N, carrying the p.L145F and the p.S135N missense variants, respectively. The patients showed diverse symptoms and disease progression in accordance with our bioinformatic analysis, which predicted the different effects of the two mutations in terms of protein structure. Interestingly, both mutations had an effect on the fibroblast energy metabolisms. However, while the SOD1L145F fibroblasts still relied more on oxidative phosphorylation, the SOD1S135N fibroblasts showed a metabolic shift toward glycolysis. Our study suggests that SOD1 mutations might lead to alterations in the energy metabolism.

Published
2022

25. Characterization of the p.L145F and p.S135N Mutations in SOD1: Impact on the Metabolism of Fibroblasts Derived from Amyotrophic Lateral Sclerosis Patients

Author

Perciballi, E., Bovio, F., Rosati, J., Arrigoni, F., D'Anzi, A., Lattante, Serena, Gelati, M., De Marchi, F., Lombardi, I., Ruotolo, G., Forcella, M., Mazzini, L., D'Alfonso, S., Corrado, L., Sabatelli, Mario, Conte, A., De Gioia, L., Martino, S., Vescovi, A. L., Fusi, P., Ferrari, D., Lattante S. (ORCID:0000-0003-2891-0340), Sabatelli M. (ORCID:0000-0001-6635-4985), Perciballi, E., Bovio, F., Rosati, J., Arrigoni, F., D'Anzi, A., Lattante, Serena, Gelati, M., De Marchi, F., Lombardi, I., Ruotolo, G., Forcella, M., Mazzini, L., D'Alfonso, S., Corrado, L., Sabatelli, Mario, Conte, A., De Gioia, L., Martino, S., Vescovi, A. L., Fusi, P., Ferrari, D., Lattante S. (ORCID:0000-0003-2891-0340), and Sabatelli M. (ORCID:0000-0001-6635-4985)

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of the upper and lower motor neurons (MNs). About 10% of patients have a family history (familial, fALS); however, most patients seem to develop the sporadic form of the disease (sALS). SOD1 (Cu/Zn superoxide dismutase-1) is the first studied gene among the ones related to ALS. Mutant SOD1 can adopt multiple misfolded conformation, lose the correct coordination of metal binding, decrease structural stability, and form aggregates. For all these reasons, it is complicated to characterize the conformational alterations of the ALS-associated mutant SOD1, and how they relate to toxicity. In this work, we performed a multilayered study on fibroblasts derived from two ALS patients, namely SOD1L145F and SOD1S135N, carrying the p.L145F and the p.S135N missense variants, respectively. The patients showed diverse symptoms and disease progression in accordance with our bioinformatic analysis, which predicted the different effects of the two mutations in terms of protein structure. Interestingly, both mutations had an effect on the fibroblast energy metabolisms. However, while the SOD1L145F fibroblasts still relied more on oxidative phosphorylation, the SOD1S135N fibroblasts showed a metabolic shift toward glycolysis. Our study suggests that SOD1 mutations might lead to alterations in the energy metabolism.

Published
2022

28. Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology (vol 53, pg 1636, 2021)

Author

van Rheenen, W, van der Spek, RAA, Bakker, MK, van Vugt, JJFA, Hop, PJ, Zwamborn, RAJ, de Klein, N, Westra, HJ, Bakker, OB, Deelen, P, Shireby, G, Hannon, E, Moisse, M, Baird, D, Restuadi, R, Dolzhenko, E, Dekker, AM, Gawor, K, Westeneng, HJ, Tazelaar, GHP, van Eijk, KR, Kooyman, M, Byrne, RP, Doherty, M, Heverin, M, Al Khleifat, A, Iacoangeli, A, Shatunov, A, Ticozzi, N, Cooper-Knock, J, Smith, BN, Gromicho, M, Chandran, S, Pal, S, Morrison, KE, Shaw, PJ, Hardy, J, Orrell, RW, Sendtner, M, Meyer, T, Basak, N, van der Kooi, AJ, Ratti, A, Fogh, I, Gellera, C, Lauria, G, Corti, S, Cereda, C, Sproviero, D, Soraru, G, Siciliano, G, Filosto, M, Padovani, A, Chio, A, Calvo, A, Moglia, C, Brunetti, M, Canosa, A, Grassano, M, Beghi, E, Pupillo, E, Logroscino, G, Nefussy, B, Osmanovic, A, Nordin, A, Lerner, Y, Zabari, M, Gotkine, M, Baloh, RH, Bell, S, Vourc'h, P, Corcia, P, Couratier, P, Millecamps, S, Meininger, V, Salachas, F, Pardina, JMS, Assialioui, A, Rojas-Garcia, R, Dion, PA, Ross, JP, Ludolph, AC, Weishaupt, JH, Brenner, D, Freischmidt, A, Bensimon, G, Brice, A, Durr, A, Payan, CAM, Saker-Delye, S, Wood, NW, Topp, S, Rademakers, R, Tittmann, L, Lieb, W, Franke, A, Ripke, S, Braun, A, Kraft, J, Whiteman, DC, Olsen, CM, Uitterlinden, AG, Hofman, A, Rietschel, M, Cichon, S, Nothen, MM, Amouyel, P, Comi, G, Riva, N, Lunetta, C, Gerardi, F, Cotelli, MS, Rinaldi, F, Chiveri, L, Guaita, MC, Perrone, P, Diamanti, L, Ferrarese, C, Tremolizzo, L, Delodovici, ML, Bono, G, Manera, U, Vasta, R, Bombaci, A, Casale, F, Fuda, G, Salamone, P, Iazzolino, B, Peotta, L, Cugnasco, P, De Marco, G, Torrieri, MC, Palumbo, F, Gallone, S, Barberis, M, Sbaiz, L, Gentile, S, Mauro, A, De Marchi, F, D'Alfonso, S, Bertolotto, A, Gionco, M, Leotta, D, Odddenino, E, Imperiale, D, Cavallo, R, Pignatta, P, De Mattei, M, Geda, C, Papurello, DM, Gusmaroli, G, Comi, C, Labate, C, Ruiz, L, Ferrandi, D, Rota, E, Aguggia, M, Di Vito, N, Meineri, P, Ghiglione, P, Launaro, N, Dotta, M, Di Sapio, A, Giardini, G, Tiloca, C, Peverelli, S, Taroni, F, Pensato, V, Castellotti, B, Comi, GP, Del Bo, R, Ceroni, M, Gagliardi, S, Corrado, L, Mazzini, L, Raggi, F, Simoncini, C, Lo Gerfo, A, Inghilleri, M, Ferlini, A, Simone, IL, Passarella, B, Guerra, V, Zoccolella, S, Nozzoli, C, Mundi, C, Leone, M, Zarrelli, M, Tamma, F, Valluzzi, F, Calabrese, G, Boero, G, Rini, A, Traynor, BJ, Singleton, AB, Neto, MM, Cauchi, RJ, Ophoff, RA, Wiedau-Pazos, M, Lomen-Hoerth, C, van Deerlin, VM, Grosskreutz, J, Roediger, A, Gaur, N, Jork, A, Barthel, T, Theele, E, Ilse, B, Stubendorff, B, Witte, OW, Steinbach, R, Hubner, CA, Graff, C, Brylev, L, Fominykh, V, Demeshonok, V, Ataulina, A, Rogelj, B, Koritnik, B, Zidar, J, Ravnik-Glavac, M, Glavac, D, Stevic, Z, Drory, V, Povedano, M, Blair, IP, Kiernan, MC, Benyamin, B, Henderson, RD, Furlong, S, Mathers, S, McCombe, PA, Needham, M, Ngo, ST, Nicholson, GA, Pamphlett, R, Rowe, DB, Steyn, FJ, Williams, KL, Mather, KA, Sachdev, PS, Henders, AK, Wallace, L, de Carvalho, M, Pinto, S, Petri, S, Weber, M, Rouleau, GA, Silani, V, Curtis, CJ, Breen, G, Glass, JD, Brown, RH, Landers, JE, Shaw, CE, Andersen, PM, Groen, EJN, van Es, MA, Pasterkamp, RJ, Fan, DS, Garton, FC, McRae, AF, Smith, GD, Gaunt, TR, Eberle, MA, Mill, J, McLaughlin, RL, Hardiman, O, Kenna, KP, Wray, NR, Tsai, EL, Runz, H, Franke, L, Al-Chalabi, A, Van Damme, P, van den Berg, LH, Veldink, JH, SLALOM Consortium, PARALS Consortium, SLAGEN Consortium, and SLAP Consortium

Published
2022

29. Author Correction: Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology (Nature Genetics, (2021), 53, 12, (1636-1648), 10.1038/s41588-021-00973-1)

Author

van Rheenen, W., van der Spek, R. A. A., Bakker, M. K., van Vugt, J. J. F. A., Hop, P. J., Zwamborn, R. A. J., de Klein, N., Westra, H. -J., Bakker, O. B., Deelen, P., Shireby, G., Hannon, E., Moisse, M., Baird, D., Restuadi, R., Dolzhenko, E., Dekker, A. M., Gawor, K., Westeneng, H. -J., Tazelaar, G. H. P., van Eijk, K. R., Kooyman, M., Byrne, R. P., Doherty, M., Heverin, M., Al Khleifat, A., Iacoangeli, A., Shatunov, A., Ticozzi, N., Cooper-Knock, J., Smith, B. N., Gromicho, M., Chandran, S., Pal, S., Morrison, K. E., Shaw, P. J., Hardy, J., Orrell, R. W., Sendtner, M., Meyer, T., Basak, N., van der Kooi, A. J., Ratti, A., Fogh, I., Gellera, C., Lauria, G., Corti, S., Cereda, C., Sproviero, D., D'Alfonso, S., Soraru, G., Siciliano, G., Filosto, M., Padovani, A., Chio, A., Calvo, A., Moglia, C., Brunetti, M., Canosa, A., Grassano, M., Beghi, E., Pupillo, E., Logroscino, G., Nefussy, B., Osmanovic, A., Nordin, A., Lerner, Y., Zabari, M., Gotkine, M., Baloh, R. H., Bell, S., Vourc'H, P., Corcia, P., Couratier, P., Millecamps, S., Meininger, V., Salachas, F., Mora Pardina, J. S., Assialioui, A., Rojas-Garcia, R., Dion, P. A., Ross, J. P., Ludolph, A. C., Weishaupt, J. H., Brenner, D., Freischmidt, A., Bensimon, G., Brice, A., Durr, A., Payan, C. A. M., Saker-Delye, S., Wood, N. W., Topp, S., Rademakers, R., Tittmann, L., Lieb, W., Franke, A., Ripke, S., Braun, A., Kraft, J., Whiteman, D. C., Olsen, C. M., Uitterlinden, A. G., Hofman, A., Rietschel, M., Cichon, S., Nothen, M. M., Amouyel, P., Comi, G., Riva, N., Lunetta, C., Gerardi, F., Cotelli, M. S., Rinaldi, F., Chiveri, L., Guaita, M. C., Perrone, P., Ceroni, M., Diamanti, L., Ferrarese, C., Tremolizzo, L., Delodovici, M. L., Bono, G., Manera, U., Vasta, R., Bombaci, A., Casale, F., Fuda, G., Salamone, P., Iazzolino, B., Peotta, L., Cugnasco, P., De Marco, G., Torrieri, M. C., Palumbo, F., Gallone, S., Barberis, M., Sbaiz, L., Gentile, S., Mauro, A., Mazzini, L., De Marchi, F., Corrado, L., Bertolotto, A., Gionco, M., Leotta, D., Odddenino, E., Imperiale, D., Cavallo, R., Pignatta, P., De Mattei, M., Geda, C., Papurello, D. M., Gusmaroli, G., Comi, C., Labate, C., Ruiz, L., Ferrandi, D., Rota, E., Aguggia, M., Di Vito, N., Meineri, P., Ghiglione, P., Launaro, N., Dotta, M., Di Sapio, A., Giardini, G., Tiloca, C., Peverelli, S., Taroni, F., Pensato, V., Castellotti, B., Comi, G. P., Del Bo, R., Gagliardi, S., Raggi, F., Simoncini, C., Lo Gerfo, A., Inghilleri, M., Ferlini, A., Simone, I. L., Passarella, B., Guerra, V., Zoccolella, S., Nozzoli, C., Mundi, C., Leone, M., Zarrelli, M., Tamma, F., Valluzzi, F., Calabrese, G., Boero, G., Rini, A., Traynor, B. J., Singleton, A. B., Mitne Neto, M., Cauchi, R. J., Ophoff, R. A., Wiedau-Pazos, M., Lomen-Hoerth, C., van Deerlin, V. M., Grosskreutz, J., Roediger, A., Gaur, N., Jork, A., Barthel, T., Theele, E., Ilse, B., Stubendorff, B., Witte, O. W., Steinbach, R., Hubner, C. A., Graff, C., Brylev, L., Fominykh, V., Demeshonok, V., Ataulina, A., Rogelj, B., Koritnik, B., Zidar, J., Ravnik-Glavac, M., Glavac, D., Stevic, Z., Drory, V., Povedano, M., Blair, I. P., Kiernan, M. C., Benyamin, B., Henderson, R. D., Furlong, S., Mathers, S., Mccombe, P. A., Needham, M., Ngo, S. T., Nicholson, G. A., Pamphlett, R., Rowe, D. B., Steyn, F. J., Williams, K. L., Mather, K. A., Sachdev, P. S., Henders, A. K., Wallace, L., de Carvalho, M., Pinto, S., Petri, S., Weber, M., Rouleau, G. A., Silani, V., Curtis, C. J., Breen, G., Glass, J. D., Brown, R. H., Landers, J. E., Shaw, C. E., Andersen, P. M., Groen, E. J. N., van Es, M. A., Pasterkamp, R. J., Fan, D., Garton, F. C., Mcrae, A. F., Davey Smith, G., Gaunt, T. R., Eberle, M. A., Mill, J., Mclaughlin, R. L., Hardiman, O., Kenna, K. P., Wray, N. R., Tsai, E., Runz, H., Franke, L., Al-Chalabi, A., Van Damme, P., van den Berg, L. H., and Veldink, J. H.

Published
2022

30. Dynamical evolution of Ge quantum dots on Si(111): From island formation to high temperature decay

Author

Genesh, N, De Marchi, F, Heun, S, Fontana, S, Belkhou, R, Purandare, R, Motta, N, Sgarlata, A, Fanfoni, M, Macleod, J, Maclean, O, and Rosei, F

Subjects
low energy electron microscopy, Settore FIS/03, GeSi heterostructures, epitaxial growth
Abstract

Heteroepitaxial growth is a process of profound fundamental importance as well as an avenue to realize nanostructures such as Ge/Si quantum dots (QDs), with appealing properties for applications in opto- and nanoelectronics. However, controlling the Ge/Si QD size, shape, and composition remains a major obstacle to their practical implementation. Here, Ge nanostructures on Si(111) were investigated in situ and in real-time by low energy electron microscopy (LEEM), enabling the observation of the transition from wetting layer formation to 3D island growth and decay. The island size, shape, and distribution depend strongly on the growth temperature. As the deposition temperature increases, the islands become larger and sparser, consistent with Brownian nucleation and capture dynamics. At 550 degrees C, two distinct Ge/Si nanostructures are formed with bright and dark appearances that correspond to flat, atoll-like and tall, faceted islands, respectively. During annealing, the faceted islands increase in size at the expense of the flat ones, indicating that the faceted islands are thermodynamically more stable. In contrast, triangular islands with uniform morphology are obtained from deposition at 600 degrees C, suggesting that the growth more closely follows the ideal shape. During annealing, the islands formed at 600 degrees C initially show no change in morphology and size and then rupture simultaneously, signaling a homogeneous chemical potential of the islands. These observations reveal the role of dynamics and energetics in the evolution of Ge/Si QDs, which can serve as a step towards the precise control over the Ge nanostructure size, shape, composition, and distribution on Si(111).

Published
2022
Full Text
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33. Correction to: SICE national survey: current state on the adoption of laparoscopic approach to the treatment of colorectal disease in Italy (Updates in Surgery, (2019), 71, 1, (77-81), 10.1007/s13304-018-0606-5)

Author

Elmore U., Vignali A., Rosati R., Valeri A., Silecchia G., Amisano M., Anania G., Andreone D., Angelone G., Baldazzi G., Bergamini C., Biondo F. G., Boni L., Brolese A., Brachet Contul R., Campagnacci R., Campanile F., Cavicchi A., Carlini M., Cola B., Cesari M., Covotta L., Cumbo P., De Manzini N., de Marchi F., de Paolis V. P., Ercolani G., Fernando M., Ferrero A., Francioni G., Garulli G., Genna M., Gianesini R., Gioffre A., Guerrieri M., Guicciardi M. A., Jovine E., Laterza E., Merigliano S., Milone M., Moretto G., Morpurgo E., Navarra G., Neri V., Ottonello R., Panebianco V., Pavanello M., Personnettaz E., Piccoli M., Priosa F., Rossi A., Sorrentino M., Tedeschi U., Testa S., Verzelli A., Vettoretto N., Violi V., Zattini P. S., Elmore, U., Vignali, A., Rosati, R., Valeri, A., Silecchia, G., Amisano, M., Anania, G., Andreone, D., Angelone, G., Baldazzi, G., Bergamini, C., Biondo, F. G., Boni, L., Brolese, A., Brachet Contul, R., Campagnacci, R., Campanile, F., Cavicchi, A., Carlini, M., Cola, B., Cesari, M., Covotta, L., Cumbo, P., De Manzini, N., de Marchi, F., de Paolis, V. P., Ercolani, G., Fernando, M., Ferrero, A., Francioni, G., Garulli, G., Genna, M., Gianesini, R., Gioffre, A., Guerrieri, M., Guicciardi, M. A., Jovine, E., Laterza, E., Merigliano, S., Milone, M., Moretto, G., Morpurgo, E., Navarra, G., Neri, V., Ottonello, R., Panebianco, V., Pavanello, M., Personnettaz, E., Piccoli, M., Priosa, F., Rossi, A., Sorrentino, M., Tedeschi, U., Testa, S., Verzelli, A., Vettoretto, N., Violi, V., and Zattini, P. S.

Abstract

Page 80, Acknowledgements section: The surname and given name of author Riccardo Brachet Contul was incorrectly published. The correct surname and given name should read as: Surname: Brachet Contul and Given Name: Riccardo.

Published
2020

36. Surface-mediated assembly, polymerization and degradation of thiophene-based monomers† †Electronic supplementary information (ESI) available: Additional STM, XPS and DFT results, higher size version of Fig. 2, 5, 8, and a discussion of chirality. See DOI: 10.1039/c8sc05267k

Author

Galeotti, G., De Marchi, F., Taerum, T., Besteiro, L. V., El Garah, M., Lipton-Duffin, J., Ebrahimi, M., Perepichka, D. F., and Rosei, F.

Subjects
Chemistry
Abstract

Temperature mapping of the different molecular phases of tribromoterthienobenzene on (111) coinage metals., Ullmann coupling of halogenated aromatics is widely used in on-surface synthesis of two-dimensional (2D) polymers and graphene nanoribbons. It stands out among other reactions for regioselectively connecting aromatic monomers into 1D and 2D π-conjugated polymers, whose final structure and properties are determined by the initial building blocks. Thanks to their exceptional electronic properties, thiophene-containing monomers are frequently used for the synthesis of various conjugated materials. On the other hand, their use in on-surface polymerization is hampered by the possibility of ring opening when adsorbed on metal surfaces. In the present work, we mapped the temperature regime for these two competing reactions by investigating the adsorption of a thiophene-based prochiral molecule using scanning tunneling microscopy, X-ray photoelectron spectroscopy and density functional theory calculations. We followed the formation of organometallic (OM) networks, their evolution into covalent structures and the competition between C–C coupling and thiophene ring opening. The effect of surface reactivity was explored by comparing the adsorption on three (111) coinage metal substrates, namely Au, Ag and Cu. While outlining strategies to minimize the ring opening reaction, we found that the surface temperature during deposition is of paramount importance for the preparation of 2D OM networks, greatly enhancing the overall ordering of the product by depositing on hot Ag surface. Notably, the same protocol permits the creation of OM structures on the air-stable Au surface, thereby allowing the synthesis and application of 2D OM networks outside the ultra-high vacuum environment.

Published
2019

37. Gravity, Geodesy and Fundamental Physics with BepiColombo’s MORE Investigation

Author

UCL - SST/ELI/ELIC - Earth & Climate, Iess, L., Asmar, S. W., Cappuccio, P., Cascioli, G., De Marchi, F., di Stefano, I., Genova, A., Ashby, N., Barriot, J. P., Bender, P., Benedetto, C., Border, J. S., Budnik, F., Ciarcia, S., Damour, T., Dehant, V., Di Achille, G., Di Ruscio, A., Fienga, A., Formaro, R., Klioner, S., Konopliv, A., Lemaître, A., Longo, F., Mercolino, M., Mitri, G., Notaro, V., Olivieri, A., Paik, M., Palli, A., Schettino, G., Serra, D., Simone, L., Tommei, G., Tortora, P., Van Hoolst, T., Vokrouhlický, D., Watkins, M., Wu, X., Zannoni, M., UCL - SST/ELI/ELIC - Earth & Climate, Iess, L., Asmar, S. W., Cappuccio, P., Cascioli, G., De Marchi, F., di Stefano, I., Genova, A., Ashby, N., Barriot, J. P., Bender, P., Benedetto, C., Border, J. S., Budnik, F., Ciarcia, S., Damour, T., Dehant, V., Di Achille, G., Di Ruscio, A., Fienga, A., Formaro, R., Klioner, S., Konopliv, A., Lemaître, A., Longo, F., Mercolino, M., Mitri, G., Notaro, V., Olivieri, A., Paik, M., Palli, A., Schettino, G., Serra, D., Simone, L., Tommei, G., Tortora, P., Van Hoolst, T., Vokrouhlický, D., Watkins, M., Wu, X., and Zannoni, M.

Abstract

Gravity, geodesy and fundamental physics with BepiColombo’s MORE investigation for understanding Mercury's interior.

Published
2021

38. Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author

van Rheenen, W., van der Spek, R.A.A., Bakker, M.K., van Vugt, J.J.F.A., Hop, P.J., Zwamborn, R.A.J., de Klein, N., Westra, H-J, Bakker, O.B., Deelen, P., Shireby, G., Hannon, E., Moisse, M., Baird, D., Restuadi, R., Dolzhenko, E., Dekker, A.M., Gawor, K., Westeneng, H-J, Tazelaar, G.H.P., van Eijk, K.R., Kooyman, M., Byrne, R.P., Doherty, M., Heverin, M., Al Khleifat, A., Iacoangeli, A., Shatunov, A., Ticozzi, N., Cooper-Knock, J., Smith, B.N., Gromicho, M., Chandran, S., Pal, S., Morrison, K.E., Shaw, P.J., Hardy, J., Orrell, R.W., Sendtner, M., Meyer, T., Başak, N., van der Kooi, A.J., Ratti, A., Fogh, I., Gellera, C., Lauria, G., Corti, S., Cereda, C., Sproviero, D., D’alfonso, S., Sorarù, G., Siciliano, G., Filosto, M., Padovani, A., Chio, A., Calvo, A., Moglia, C., Brunetti, M., Canosa, A., Grassano, M., Beghi, E., Pupillo, E., Logroscino, G., Nefussy, B., Osmanovic, A., Nordin, A., Lerner, Y., Zabari, M., Gotkine, M., Baloh, R.H., Bell, S., Vourc’h, P., Corcia, P., Couratier, P., Millecamps, S., Meininger, V., Salachas, F., Mora Pardina, J.S., Assialioui, A., Rojas-García, R., Dion, P.A., Ross, J.P., Ludolph, A.C., Weishaupt, J.H., Brenner, D., Freischmidt, A., Bensimon, G., Brice, A., Durr, A., Payan, C.A.M., Saker-Delye, S., Wood, N.W., Topp, S., Rademakers, R., Tittmann, L., Lieb, W., Franke, A., Ripke, S., Braun, A., Kraft, J., Whiteman, D.C., Olsen, C.M., Uitterlinden, A.G., Hofman, A., Rietschel, M., Cichon, S., Nöthen, M.M., Amouyel, P., Comi, G., Riva, N., Lunetta, C., Gerardi, F., Cotelli, M.S., Rinaldi, F., Chiveri, L., Guaita, M.C., Perrone, P., Ceroni, M., Diamanti, L., Ferrarese, C., Tremolizzo, L., Delodovici, M.L., Bono, G., Manera, U., Vasta, R., Bombaci, A., Casale, F., Fuda, G., Salamone, P., Iazzolino, B., Peotta, L., Cugnasco, P., De Marco, G., Torrieri, M.C., Palumbo, F., Gallone, S., Barberis, M., Sbaiz, L., Gentile, S., Mauro, A., Mazzini, L., De Marchi, F., Corrado, L., D’Alfonso, S., Bertolotto, A., Gionco, M., Leotta, D., Odddenino, E., Imperiale, D., Cavallo, R., Pignatta, P., De Mattei, M., Geda, C., Papurello, D.M., Gusmaroli, G., Comi, C., Labate, C., Ruiz, L., Ferrandi, D., Rota, E., Aguggia, M., Di Vito, N., Meineri, P., Ghiglione, P., Launaro, N., Dotta, M., di Sapio, A., Giardini, G., Tiloca, C., Peverelli, S., Taroni, F., Pensato, V., Castellotti, B., Comi, G.P., Del Bo, R., Gagliardi, S., Raggi, F., Simoncini, C., Lo Gerfo, A., Inghilleri, M., Ferlini, A., Simone, I.L., Passarella, B., Guerra, V., Zoccolella, S., Nozzoli, C., Mundi, C., Leone, M., Zarrelli, M., Tamma, F., Valluzzi, F., Calabrese, G., Boero, G., Rini, A., Traynor, B.J., Singleton, A.B., Mitne Neto, M., Cauchi, R.J., Ophoff, R.A., Wiedau-Pazos, M., Lomen-Hoerth, C., van Deerlin, V.M., Grosskreutz, J., Roediger, A., Gaur, N., Jörk, A., Barthel, T., Theele, E., Ilse, B., Stubendorff, B., Witte, O.W., Steinbach, R., Hübner, C.A., Graff, C., Brylev, L., Fominykh, V., Demeshonok, V., Ataulina, A., Rogelj, B., Koritnik, B., Zidar, J., Ravnik-Glavač, M., Glavač, D., Stević, Z., Drory, V., Povedano, M., Blair, I.P., Kiernan, M.C., Benyamin, B., Henderson, R.D., Furlong, S., Mathers, S., McCombe, P.A., Needham, M., Ngo, S.T., Nicholson, G.A., Pamphlett, R., Rowe, D.B., Steyn, F.J., Williams, K.L., Mather, K.A., Sachdev, P.S., Henders, A.K., Wallace, L., de Carvalho, M., Pinto, S., Petri, S., Weber, M., Rouleau, G.A., Silani, V., Curtis, C.J., Breen, G., Glass, J.D., Brown, R.H., Landers, J.E., Shaw, C.E., Andersen, P.M., Groen, E.J.N., van Es, M.A., Pasterkamp, R.J., Fan, D., Garton, F.C., McRae, A.F., Davey Smith, G., Gaunt, T.R., Eberle, M.A., Mill, J., McLaughlin, R.L., Hardiman, O., Kenna, K.P., Wray, N.R., Tsai, E., Runz, H., Franke, L., Al-Chalabi, A., Van Damme, P., van den Berg, L.H., Veldink, J.H., van Rheenen, W., van der Spek, R.A.A., Bakker, M.K., van Vugt, J.J.F.A., Hop, P.J., Zwamborn, R.A.J., de Klein, N., Westra, H-J, Bakker, O.B., Deelen, P., Shireby, G., Hannon, E., Moisse, M., Baird, D., Restuadi, R., Dolzhenko, E., Dekker, A.M., Gawor, K., Westeneng, H-J, Tazelaar, G.H.P., van Eijk, K.R., Kooyman, M., Byrne, R.P., Doherty, M., Heverin, M., Al Khleifat, A., Iacoangeli, A., Shatunov, A., Ticozzi, N., Cooper-Knock, J., Smith, B.N., Gromicho, M., Chandran, S., Pal, S., Morrison, K.E., Shaw, P.J., Hardy, J., Orrell, R.W., Sendtner, M., Meyer, T., Başak, N., van der Kooi, A.J., Ratti, A., Fogh, I., Gellera, C., Lauria, G., Corti, S., Cereda, C., Sproviero, D., D’alfonso, S., Sorarù, G., Siciliano, G., Filosto, M., Padovani, A., Chio, A., Calvo, A., Moglia, C., Brunetti, M., Canosa, A., Grassano, M., Beghi, E., Pupillo, E., Logroscino, G., Nefussy, B., Osmanovic, A., Nordin, A., Lerner, Y., Zabari, M., Gotkine, M., Baloh, R.H., Bell, S., Vourc’h, P., Corcia, P., Couratier, P., Millecamps, S., Meininger, V., Salachas, F., Mora Pardina, J.S., Assialioui, A., Rojas-García, R., Dion, P.A., Ross, J.P., Ludolph, A.C., Weishaupt, J.H., Brenner, D., Freischmidt, A., Bensimon, G., Brice, A., Durr, A., Payan, C.A.M., Saker-Delye, S., Wood, N.W., Topp, S., Rademakers, R., Tittmann, L., Lieb, W., Franke, A., Ripke, S., Braun, A., Kraft, J., Whiteman, D.C., Olsen, C.M., Uitterlinden, A.G., Hofman, A., Rietschel, M., Cichon, S., Nöthen, M.M., Amouyel, P., Comi, G., Riva, N., Lunetta, C., Gerardi, F., Cotelli, M.S., Rinaldi, F., Chiveri, L., Guaita, M.C., Perrone, P., Ceroni, M., Diamanti, L., Ferrarese, C., Tremolizzo, L., Delodovici, M.L., Bono, G., Manera, U., Vasta, R., Bombaci, A., Casale, F., Fuda, G., Salamone, P., Iazzolino, B., Peotta, L., Cugnasco, P., De Marco, G., Torrieri, M.C., Palumbo, F., Gallone, S., Barberis, M., Sbaiz, L., Gentile, S., Mauro, A., Mazzini, L., De Marchi, F., Corrado, L., D’Alfonso, S., Bertolotto, A., Gionco, M., Leotta, D., Odddenino, E., Imperiale, D., Cavallo, R., Pignatta, P., De Mattei, M., Geda, C., Papurello, D.M., Gusmaroli, G., Comi, C., Labate, C., Ruiz, L., Ferrandi, D., Rota, E., Aguggia, M., Di Vito, N., Meineri, P., Ghiglione, P., Launaro, N., Dotta, M., di Sapio, A., Giardini, G., Tiloca, C., Peverelli, S., Taroni, F., Pensato, V., Castellotti, B., Comi, G.P., Del Bo, R., Gagliardi, S., Raggi, F., Simoncini, C., Lo Gerfo, A., Inghilleri, M., Ferlini, A., Simone, I.L., Passarella, B., Guerra, V., Zoccolella, S., Nozzoli, C., Mundi, C., Leone, M., Zarrelli, M., Tamma, F., Valluzzi, F., Calabrese, G., Boero, G., Rini, A., Traynor, B.J., Singleton, A.B., Mitne Neto, M., Cauchi, R.J., Ophoff, R.A., Wiedau-Pazos, M., Lomen-Hoerth, C., van Deerlin, V.M., Grosskreutz, J., Roediger, A., Gaur, N., Jörk, A., Barthel, T., Theele, E., Ilse, B., Stubendorff, B., Witte, O.W., Steinbach, R., Hübner, C.A., Graff, C., Brylev, L., Fominykh, V., Demeshonok, V., Ataulina, A., Rogelj, B., Koritnik, B., Zidar, J., Ravnik-Glavač, M., Glavač, D., Stević, Z., Drory, V., Povedano, M., Blair, I.P., Kiernan, M.C., Benyamin, B., Henderson, R.D., Furlong, S., Mathers, S., McCombe, P.A., Needham, M., Ngo, S.T., Nicholson, G.A., Pamphlett, R., Rowe, D.B., Steyn, F.J., Williams, K.L., Mather, K.A., Sachdev, P.S., Henders, A.K., Wallace, L., de Carvalho, M., Pinto, S., Petri, S., Weber, M., Rouleau, G.A., Silani, V., Curtis, C.J., Breen, G., Glass, J.D., Brown, R.H., Landers, J.E., Shaw, C.E., Andersen, P.M., Groen, E.J.N., van Es, M.A., Pasterkamp, R.J., Fan, D., Garton, F.C., McRae, A.F., Davey Smith, G., Gaunt, T.R., Eberle, M.A., Mill, J., McLaughlin, R.L., Hardiman, O., Kenna, K.P., Wray, N.R., Tsai, E., Runz, H., Franke, L., Al-Chalabi, A., Van Damme, P., van den Berg, L.H., and Veldink, J.H.

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.

Published
2021

39. Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author

Başak, Ayşe Nazlı (ORCID 0000-0001-9257-3540 & YÖK ID 1512), van Rheenen, W.; Van der Spek, R.A.A.; Bakker, M.K.; van Vugt, J.J.F.A.; Hop, P.J.; Zwamborn, R.A.J.; de Klein, N.; Westra, H.J.; Bakker, O.B.; Deelen, P.; Shireby, G.; Hannon, E.; Moisse, M.; Baird, D.; Restuadi, R.; Dolzhenko, E.; Dekker, A.M.; Gawor, K.; Westeneng, H.J.; Tazelaar, G.H.P.; van Eijk, K.R.; Kooyman, M.; Byrne, R.P.; Doherty, M.; Heverin, M.; Al Khleifat, A.; Iacoangeli, A.; Shatunov, A.; Ticozzi, N.; Cooper-Knock, J.; Smith, B.N.; Gromicho, M.; Chandran, S.; Pal, S.; Morrison, K.E.; Shaw, P.J.; Hardy, J.; Orrell, R.W.; Sendtner, M.; Meyer, T.; van der Kooi, A.J.; Ratti, A.; Fogh, I.; Gellera, C.; Lauria, G.; Corti, S.; Cereda, C.; Sproviero, D.; D'Alfonso, S.; Sorarù, G.; Siciliano, G.; Filosto, M.; Padovani, A.; Chiò, A.; Calvo, A.; Moglia, C.; Brunetti, M.; Canosa, A.; Grassano, M.; Beghi, E.; Pupillo, E.; Logroscino, G.; Nefussy, B.; Osmanovic, A.; Nordin, A.; Lerner, Y.; Zabari, M.; Gotkine, M.; Baloh, R.H.; Bell, S.; Vourc'h, P.; Corcia, P.; Couratier, P.; Millecamps, S.; Meininger, V.; Salachas, F.; Mora Pardina, J.S.; Assialioui, A.; Rojas-García, R.; Dion, P.A.; Ross, J.P.; Ludolph, A.C.; Weishaupt, J.H.; Brenner, D.; Freischmidt, A.; Bensimon, G.; Brice, A.; Durr, A.; Payan, C.A.M.; Saker-Delye, S.; Wood, N.W.; Topp, S.; Rademakers, R.; Tittmann, L.; Lieb, W.; Franke, A.; Ripke, S.; Braun, A; Kraft, J.,Whiteman, David C.; Olsen, Catherine M.; Uitterlinden, A.G.; Hofman, A.; Rietschel, M.; Cichon, S.; Nothen, M.M.; Amouyel, P.; Comi, G.; Riva, N.; Lunetta, C.; Gerardi, F.; Cotelli, M.S.; Rinaldi, F.; Chiveri, L.; Guaita, M.C.; Perrone, P.; Ceroni, M.; Diamanti, L.; Ferrarese, C.; Tremolizzo, L.; Delodovici, M.L.; Bono, G.; Manera, U.; Vasta, R.; Bombaci, A.; Casale, F.; Fuda, G.; Salamone, P.; Iazzolino, B.; Peotta, L.; Cugnasco, P.; De Marco, G.; Torrieri, M.C.; Palumbo, F.; Gallone, S.; Barberis, M.; Sbaiz, L.; Gentile, S.; Mauro, A.; Mazzini, L.; De Marchi, F.; Corrado, L.; D'Alfonso, S.; Bertolotto, A.; Gionco, M.; Leotta, D.; Odddenino, Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), School of Medicine, Başak, Ayşe Nazlı (ORCID 0000-0001-9257-3540 & YÖK ID 1512), van Rheenen, W.; Van der Spek, R.A.A.; Bakker, M.K.; van Vugt, J.J.F.A.; Hop, P.J.; Zwamborn, R.A.J.; de Klein, N.; Westra, H.J.; Bakker, O.B.; Deelen, P.; Shireby, G.; Hannon, E.; Moisse, M.; Baird, D.; Restuadi, R.; Dolzhenko, E.; Dekker, A.M.; Gawor, K.; Westeneng, H.J.; Tazelaar, G.H.P.; van Eijk, K.R.; Kooyman, M.; Byrne, R.P.; Doherty, M.; Heverin, M.; Al Khleifat, A.; Iacoangeli, A.; Shatunov, A.; Ticozzi, N.; Cooper-Knock, J.; Smith, B.N.; Gromicho, M.; Chandran, S.; Pal, S.; Morrison, K.E.; Shaw, P.J.; Hardy, J.; Orrell, R.W.; Sendtner, M.; Meyer, T.; van der Kooi, A.J.; Ratti, A.; Fogh, I.; Gellera, C.; Lauria, G.; Corti, S.; Cereda, C.; Sproviero, D.; D'Alfonso, S.; Sorarù, G.; Siciliano, G.; Filosto, M.; Padovani, A.; Chiò, A.; Calvo, A.; Moglia, C.; Brunetti, M.; Canosa, A.; Grassano, M.; Beghi, E.; Pupillo, E.; Logroscino, G.; Nefussy, B.; Osmanovic, A.; Nordin, A.; Lerner, Y.; Zabari, M.; Gotkine, M.; Baloh, R.H.; Bell, S.; Vourc'h, P.; Corcia, P.; Couratier, P.; Millecamps, S.; Meininger, V.; Salachas, F.; Mora Pardina, J.S.; Assialioui, A.; Rojas-García, R.; Dion, P.A.; Ross, J.P.; Ludolph, A.C.; Weishaupt, J.H.; Brenner, D.; Freischmidt, A.; Bensimon, G.; Brice, A.; Durr, A.; Payan, C.A.M.; Saker-Delye, S.; Wood, N.W.; Topp, S.; Rademakers, R.; Tittmann, L.; Lieb, W.; Franke, A.; Ripke, S.; Braun, A; Kraft, J.,Whiteman, David C.; Olsen, Catherine M.; Uitterlinden, A.G.; Hofman, A.; Rietschel, M.; Cichon, S.; Nothen, M.M.; Amouyel, P.; Comi, G.; Riva, N.; Lunetta, C.; Gerardi, F.; Cotelli, M.S.; Rinaldi, F.; Chiveri, L.; Guaita, M.C.; Perrone, P.; Ceroni, M.; Diamanti, L.; Ferrarese, C.; Tremolizzo, L.; Delodovici, M.L.; Bono, G.; Manera, U.; Vasta, R.; Bombaci, A.; Casale, F.; Fuda, G.; Salamone, P.; Iazzolino, B.; Peotta, L.; Cugnasco, P.; De Marco, G.; Torrieri, M.C.; Palumbo, F.; Gallone, S.; Barberis, M.; Sbaiz, L.; Gentile, S.; Mauro, A.; Mazzini, L.; De Marchi, F.; Corrado, L.; D'Alfonso, S.; Bertolotto, A.; Gionco, M.; Leotta, D.; Odddenino, Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), and School of Medicine

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons., Dutch Research Council (NWO); VENI Scheme Grant; VIDI Grant; Prinses Beatrix Spierfonds; Neuromuscular Fellowship Grant; Medical Research Council (MRC); Clinical Infrastructure Award; Epidemiology Unit; Integrative Epidemiology Unit; Canadian Institutes of Health Research; IWT; National Institute on Aging; National Health and Medical Research Council (NHMRC); Enabling Grant; NHMRC/Australian Research Council Strategic Award; NHMRC; NHMRC Centre of Research Excellence Grant; National Health and Medical Research Council of Australia (NHMRC) Research Fellowship; United Kingdom, Medical Research Council; Economic and Social Research Council; European Union (EU); Horizon 2020; European Community's Health Seventh Framework Programme; EuroMOTOR; European Research Council (ERC); Research and Innovation Programme; EScORIAL; ALS Foundation Netherlands; Alzheimer’s Society PhD Studentship; ARSla Funding; Biogen; University of Bristol; Motor Neurone Disease Association (MNDA); NIHR Maudsley Biomedical Research Centre; Dutch Ministry of Education, Culture, and Science; Netherlands Organization for Scientific Research (NWO; BRAINSCAPES); Gravitation Program; ALS Liga België; National Lottery of Belgium; KU Leuven Opening the Future Fund; KU Leuven Funds, “Een Hart voor ALS”, “Laeversfonds voor ALS Onderzoek” and the “Valéry Perrier Race against ALS Fund”; E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders; ALS Liga België; “Live now” Charity Foundation; Moscow ALS palliative Care Service; Canadian Institutes of Health; Research Australia; Ice Bucket Challenge Grant; NIH Intramural Research Programs; FightMND Mid-Career Fellowship; NIHR Senior Investigator; Sheffield NIHR Biomedical Research Centre; Motor Neurone Disease Association; National Institute for Health Research (NIHR) Biomedical Research Centre; Maudsley NHS Foundation Trust; King’s College London; NIHR Senior Investigator Award; Netherlands Organization for Health Research and Development; Vici Sche

Published
2021

40. C9ORF72 repeat expansion affects the proteome of primary skin fibroblasts in ALS

Author

Lualdi, M., Shafique, A., Pedrini, E., Pieroni, L., Greco, Viviana, Castagnola, M., Cucina, G., Corrado, L., Di Pierro, A., De Marchi, F., Camillo, L., Colombrita, C., D'Anca, M., Alberio, T., D'Alfonso, S., Fasano, M., Greco V. (ORCID:0000-0003-4521-0020), Lualdi, M., Shafique, A., Pedrini, E., Pieroni, L., Greco, Viviana, Castagnola, M., Cucina, G., Corrado, L., Di Pierro, A., De Marchi, F., Camillo, L., Colombrita, C., D'Anca, M., Alberio, T., D'Alfonso, S., Fasano, M., and Greco V. (ORCID:0000-0003-4521-0020)

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by pro-gressive degeneration of the corticospinal motor neurons, which ultimately leads to death. The repeat expansion in chromosome 9 open reading frame 72 (C9ORF72) represents the most common genetic cause of ALS and it is also involved in the pathogenesis of other neurodegenerative disorders. To offer insights into C9ORF72-mediated pathogenesis, we quantitatively analyzed the proteome of patient-derived primary skin fibroblasts from ALS patients carrying the C9ORF72 mutation compared with ALS patients who tested negative for it. Differentially expressed proteins were identified, used to generate a protein-protein interaction network and subjected to a functional enrichment analysis to unveil altered molecular pathways. ALS patients were also compared with patients affected by frontotemporal dementia carrying the C9ORF72 repeat expansion. As a result, we demonstrated that the molecular pathways mainly altered in fibroblasts (e.g., protein homeostasis) mirror the alterations observed in C9ORF72-mutated neurons. Moreover, we highlighted novel molecular pathways (nuclear and mitochondrial transports, vesicle trafficking, mitochondrial bioenergetics, glucose metabolism, ER-phagosome crosstalk and Slit/Robo signaling pathway) which might be further investigated as C9ORF72-specific pathogenetic mechanisms. Data are available via ProteomeXchange with the identifier PXD023866.

Published
2021

41. Decline of cognitive and behavioral functions in amyotrophic lateral sclerosis: a longitudinal study

Author

Bersano, E, Sarnelli, M, Solara, V, Iazzolino, B, Peotta, L, De Marchi, F, Facchin, A, Moglia, C, Canosa, A, Calvo, A, Chiò, A, Mazzini, L, Bersano, Enrica, Sarnelli, Maria Francesca, Solara, Valentina, Iazzolino, Barbara, Peotta, Laura, De Marchi, Fabiola, Facchin, Alessio P, Moglia, Cristina, Canosa, Antonio, Calvo, Andrea, Chiò, Adriano, Mazzini, Letizia, Bersano, E, Sarnelli, M, Solara, V, Iazzolino, B, Peotta, L, De Marchi, F, Facchin, A, Moglia, C, Canosa, A, Calvo, A, Chiò, A, Mazzini, L, Bersano, Enrica, Sarnelli, Maria Francesca, Solara, Valentina, Iazzolino, Barbara, Peotta, Laura, De Marchi, Fabiola, Facchin, Alessio P, Moglia, Cristina, Canosa, Antonio, Calvo, Andrea, Chiò, Adriano, and Mazzini, Letizia

Abstract

Background: A cognitive impairment, ranging from frontotemporal dementia (FTD) to milder forms of dysexecutive or behavioral dysfunction, is detected in 30-50% of patients affected by amyotrophic lateral sclerosis (ALS) at diagnosis. Such condition considerably influences the prognosis, and possibly impacts on the decision-making process with regards to end-of-life choices. The aim of our study is to examine the changes of cognitive and behavioral impairment in a large population of ALS from the time of diagnosis to a 6-month follow-up (IQR 5.5-9.0 months), and to examine to what extent the progression of cognitive impairment affects survival time and rate of disease progression.Methods: We recruited 146 ALS patients classified according to revised criteria of ALS and FTD spectrum disorder. In a multidisciplinary setting, during two subsequent visits we examined clinical features with ALSFRS-r score, FVC% and BMI, and cognitive status with an extensive neuropsychological evaluation.Results: At second examination, one-third of patients showed a worsening of cognitive impairment, namely 88% of ALSbi, 27% of ALSci, 40% of ALScbi, and, interestingly, also 24% of cognitive normal ALS developed a significant cognitive dysfunction. We find that those who changed their cognitive status presented a lower ALSFRS-r score at t1 and a shorter survival time compared to those who did not change, regardless of the type of cognitive impairment.Conclusion: We show how cognitive disorders in ALS patients can not only be present at diagnosis, but also manifest during disease and influence the progression of motor deficit and the prognosis.

Published
2020

45. Analysis of DNA tandem repeats in ALS from Whole Genome Sequencing: Role of FRA10Ac1 gene repeat expansion in ALS

Author

Corrado L., Genovese L., Mangano E., Croce R., Di Pierro A., Geraci F., Bordoni R., D'Aurizio R., Barizzone N., De Marchi F., Mazzini L., De Bellis G., Manzini G., Severgnini M., Pellegrini M., and D'Alfonso S.

Subjects
Computational Biology
Abstract

The C9ORF72 gene repeat expansion is the most frequent cause of ALS. Long repeats alleles in ATXN-1, ATXN-2, and NIPA1 genes are associated to ALS susceptibility. Tandem Repeat Polymorphisms (TRPs) are good candidates for missing hereditability in ALS (40%), although they were never systematically analyzed as they represent a remarkable challenge to NGS. The aim of this study is to perform a systematic analysis of TRPs in ALS by combining NGS and novel bioinformatics tools. We performed our analysis from whole genome sequencing data (WGS) of 70 ALS cases. TRPs were evaluated by means of a software developed within our consortium to detect tandem repeat expansion. Validation of expanded loci was conducted by Repeat primer PCR We identified an ALS patient with a CGG expansion in 5'UTR of FRA10AC1 gene. To explore the possible role of this CGG expansion in ALS we screened a cohort of 337 ALS and 285 controls and we found 3 expanded patients (0.9%) and no control. We failed to replicated this result in a second cohort of 426 ALS patients and 733 controls (1 ALS (0.2%) and 5 controls (0.7%)) Overall, we observed the CGG expansion in 4/763 (0.5%) ALS patients and 5/1018 controls (0.5%). FRA10AC1 gene expression was not silenced by the expansion. The software we developed can detect epeat expansions from WGS data, although FRA10AC1 CGG expansion seems not to be involved in ALS pathogenesis. Conversely to what previously reported, large CGG expansion at this locus do not decrease gene expression

Published
2019

46. Early weight loss in amyotrophic lateral sclerosis: Outcome relevance and clinical correlates in a population-based cohort

Author

Moglia, C., Calvo, A., Grassano, M., Canosa, A., Manera, U., D'Ovidio, F., Bombaci, A., Bersano, E., Mazzini, L., Mora, G., Chio, A., Cammarosano, S., Vasta, R., Torrieri, M. C., Solero, L., Clerico, M., De Mercanti, S., Mauro, A., Pradotto, L., De Marchi, F., Sosso, L., Leotta, D., Appendino, L., Imperiale, D., Cavallo, R., Geda, C., Poglio, F., Santimaria, P., Massazza, U., Villani, A., Conti, R., Ruiz, L. C., Palermo, M., Vergnano, F., Rota, E., Penza, M. T., Aguggia, M., Meineri, P., Ghiglione, P., Launaro, N., Astegiano, G., and Corso, G.

Subjects
Male, medicine.medical_specialty, amyotrophic lateral sclerosis, dysphagia, body mass index, Logistic regression, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Weight loss, respiratory function, Internal medicine, medicine, Humans, Respiratory function, Amyotrophic lateral sclerosis, weight loss, 030304 developmental biology, Aged, 0303 health sciences, business.industry, medicine.disease, Dysphagia, Survival Analysis, Clinical trial, Psychiatry and Mental health, Cohort, Disease Progression, Surgery, Female, Neurology (clinical), medicine.symptom, business, Body mass index, 030217 neurology & neurosurgery
Abstract

ObjectivesTo assess the role of body mass index (BMI) and of the rate of weight loss as prognostic factors in amyotrophic lateral sclerosis (ALS) and to explore the clinical correlates of weight loss in the early phases of the disease.MethodsThe study cohort included all ALS patients in Piemonte/Valle d’Aosta in the 2007–2011 period. Overall survival and the probability of death/tracheostomy at 18 months (logistic regression model) were calculated.ResultsOf the 712 patients, 620 (87.1%) were included in the study. Patients ’ survival was related to the mean monthly percentage of weight loss at diagnosis (pConclusionsThe rate of weight loss from onset to diagnosis was found to be a strong and independent prognostic factor in ALS. Weight loss was mainly due to the reduction of nutritional intake related to dysphagia, but a subgroup of spinal onset patients without dysphagia at diagnosis had a severe weight loss and an outcome similar to bulbar patients. According to our findings, we recommend that in clinical trials patients should be stratified according to the presence of dysphagia at the time of enrolment and not by site of onset of symptoms.

Published
2019

49. Rapamycin treatment for amyotrophic lateral sclerosis protocol for a phase II randomized, double-blind, placebo-controlled, multicenter, clinical trial (RAP-ALS trial)

Author

Mandrioli, J., D'Amico, R., Zucchi, E., Gessani, A., Fini, N., Fasano, A., Caponnetto, C., Chio, A., Bella, E. D., Lunetta, C., Mazzini, L., Marinou, K., Soraru, G., De Biasi, S., Lo Tartaro, D., Pinti, M., Nichelli, P., Vicini, R., Cabona, C., Calvo, A., Moglia, C., Manera, U., Fuda, G., Canosa, A., Ilardi, A., Lauria, G., Dalla Bella, E., Gerardi, F., Scognamiglio, A., De Marchi, F., Mora, G., Gizzi, M., and Cossarizza, A.

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, amyotrophic lateral sclerosis, autophagy, Helsinki declaration, law.invention, 03 medical and health sciences, Randomized controlled trial, Double-Blind Method, law, Internal medicine, medicine, Humans, Rapamycin, Amyotrophic lateral sclerosis, Mechanistic target of rapamycin, Sirolimus, biology, business.industry, TOR Serine-Threonine Kinases, Medicine (all), General Medicine, medicine.disease, randomized clinical trial, Clinical trial, Survival Rate, 030104 developmental biology, Treg lymphocytes, Amyotrophic Lateral Sclerosis, Biomarkers, Immunosuppressive Agents, Italy, Quality of Life, Research Design, Treatment Outcome, Tolerability, biology.protein, business, Autophagy, Randomized clinical trial, medicine.drug
Abstract

Introduction Misfolded aggregated proteins and neuroinflammation significantly contribute to amyotrophic lateral sclerosis (ALS) pathogenesis, hence representing therapeutic targets to modify disease expression. Rapamycin inhibits mechanistic target of Rapamycin (mTOR) pathway and enhances autophagy with demonstrated beneficial effects in neurodegeneration in cell line and animal models, improving phenotype in SQSTM1 zebrafish, in Drosophila model of ALS-TDP, and in the TDP43 mouse model, in which it reduced neuronal loss and TDP43 inclusions. Rapamycin also expands regulatory T lymphocytes (Treg) and increased Treg levels are associated with slow progression in ALS patients.Therefore, we planned a randomized clinical trial testing Rapamycin treatment in ALS patients. Methods RAP-ALS is a phase II randomized, double-blind, placebo-controlled, multicenter (8 ALS centers in Italy), clinical trial. The primary aim is to assess whether Rapamycin administration increases Tregs number in treated patients compared with control arm. Secondary aims include the assessment of safety and tolerability of Rapamycin in patients with ALS; the minimum dosage to have Rapamycin in cerebrospinal fluid; changes in immunological (activation and homing of T, B, NK cell subpopulations) and inflammatory markers, and on mTOR downstream pathway (S6RP phosphorylation); clinical activity (ALS Functional Rating Scale-Revised, survival, forced vital capacity); and quality of life (ALSAQ40 scale). Discussion Rapamycin potentially targets mechanisms at play in ALS (i.e., autophagy and neuroinflammation), with promising preclinical studies. It is an already approved drug, with known pharmacokinetics, already available and therefore with significant possibility of rapid translation to daily clinics. Findings will provide reliable data for further potential trials. Ethics and dissemination The study protocol was approved by the Ethics Committee of Azienda Ospedaliero Universitaria of Modena and by the Ethics Committees of participating centers (Eudract n. 2016-002399-28) based on the Helsinki declaration.

Published
2018

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