Classifying Parkinson’s Disease Patients With Syntactic and Socio-emotional Verbal Measures

Frontostriatal disorders, such as Parkinson’s disease (PD), are characterized by progressive disruption of cortico-subcortical dopaminergic loops involved in diverse higher-order domains, including language. Indeed, syntactic and emotional language tasks have emerged as potential biomarkers of frontostriatal disturbances. However, relevant studies and models have typically considered these linguistic dimensions in isolation, overlooking the potential advantages of targeting multidimensional markers. Here, we examined whether patient classification can be improved through the joint assessment of both dimensions using sentential stimuli. We evaluated 31 early PD patients and 24 healthy controls via two syntactic measures (functional-role assignment, parsing of long-distance dependencies) and a verbal task tapping social emotions (envy, Schadenfreude) and compared their classification accuracy when analyzed in isolation and in combination. Complementarily, we replicated our approach to discriminate between patients on and off medication. Results showed that specific measures of each dimension were selectively impaired in PD. In particular, joint analysis of outcomes in functional-role assignment and Schadenfreude improved the classification accuracy of patients and controls, irrespective of their overall cognitive and affective state. These results suggest that multidimensional linguistic assessments may better capture the complexity and multi-functional impact of frontostriatal disruptions, highlighting their potential contributions in the ongoing quest for sensitive markers of PD.Fil: Baez, Sandra. Universidad de los Andes; ColombiaFil: Herrera, Eduar. Universidad Icesi; ColombiaFil: Trujillo, Catalina. Universidad del Valle; ColombiaFil: Cardona, Juan F.. Universidad del Valle; ColombiaFil: Diazgranados, Jesús A.. Centro Médico de Atención Neurológica Neurólogos de Occidente; ColombiaFil: Pino, Mariana. Universidad Autónoma del Caribe; ColombiaFil: Santamaria Garcia, Hernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Universitario San Ignacio; Colombia. Pontificia Universidad Javeriana; ColombiaFil: Ibañez, Agustin Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Autónoma del Caribe; Colombia. Universidad de San Andrés; Argentina. Universidad Adolfo Ibañez; Chile. University of California; Estados UnidosFil: García, Adolfo Martín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de San Andrés; Argentina. University of California; Estados Unidos. Universidad Catolica de Cuyo. Facultad de Educacion.; Argentin

BFF: A tool for eliciting tie strength and user communities in social networking services

The final publication is available at Springer via http://dx.doi.org/ 10.1007/s10796-013-9453-6The use of social networking services (SNSs) such as Facebook has explosively grown in the last few years. Users see these SNSs as useful tools to find friends and interact with them. Moreover, SNSs allow their users to share photos, videos, and express their thoughts and feelings. However, users are usually concerned about their privacy when using SNSs. This is because the public image of a subject can be affected by photos or comments posted on a social network. In this way, recent studies demonstrate that users are demanding better mechanisms to protect their privacy. An appropriate approximation to solve this could be a privacy assistant software agent that automatically suggests a privacy policy for any item to be shared on a SNS. The first step for developing such an agent is to be able to elicit meaningful information that can lead to accurate privacy policy predictions. In particular, the information needed is user communities and the strength of users' relationships, which, as suggested by recent empirical evidence, are the most important factors that drive disclosure in SNSs. Given the number of friends that users can have and the number of communities they may be involved on, it is infeasible that users are able to provide this information without the whole eliciting process becoming confusing and time consuming. In this work, we present a tool called Best Friend Forever (BFF) that automatically classifies the friends of a user in communities and assigns a value to the strength of the relationship ties to each one. We also present an experimental evaluation involving 38 subjects that showed that BFF can significantly alleviate the burden of eliciting communities and relationship strength.This work has been partially supported by CONSOLIDER-INGENIO 2010 under grant CSD2007-00022, and TIN 2008-04446 and PROMETEO II/2013/019 projects. This article has been developed as a result of a mobility stay funded by the Erasmus Mundus Programme of the European Comission under the Transatlantic Partnership for Excellence in Engineering - TEE Project.López Fogués, R.; Such Aparicio, JM.; Espinosa Minguet, AR.; García-Fornes, A. (2014). BFF: A tool for eliciting tie strength and user communities in social networking services. Information Systems Frontiers. 16:225-237. https://doi.org/10.1007/s10796-013-9453-6S22523716Blondel, V.D., Guillaume, J.L., Lambiotte, R., Lefebvre, E. (2008). Fast unfolding of communities in large networks. Journal of Statistical Mechanics: Theory and Experiment, 2008(10), P10008.Boyd, D., & Hargittai, E. (2010). Facebook privacy settings: who cares? First Monday, 15(8).Burt, R. (1995). Structural holes: the social structure of competition. Harvard University Pr.Culotta, A., Bekkerman, R., McCallum, A. (2004). Extracting social networks and contact information from email and the web.Ellison, N., Steinfield, C., Lampe, C. (2007). The benefits of facebook friends: social capital and college students use of online social network sites. Journal of Computer-Mediated Communication, 12(4), 1143–1168.Fang, L., & LeFevre, K. (2010). Privacy wizards for social networking sites. In Proceedings of the 19th international conference on World wide web (pp. 351–360). ACM.Fortunato, S. (2010). Community detection in graphs. Physics Reports, 486(3-5), 75–174.Gilbert, E., & Karahalios, K. (2009). Predicting tie strength with social media. In Proceedings of the 27th international conference on human factors in computing systems (pp. 211–220). ACM.Girvan, M., & Newman, M. (2002). Community structure in social and biological networks. Proceedings of the National Academy of Science, 99(12), 7821.Granovetter, M. (1973). The strength of weak ties. American Journal of Sociology, 1360–1380.Gross, R., & Acquisti, A. (2005). Information revelation and privacy in online social networks. In Proceedings of the 2005 ACM workshop on privacy in the electronic society (pp. 71–80). ACM.Johnson, M., Egelman, S., Bellovin, S. (2012). Facebook and privacy: it’s complicated. In Proceedings of the eighth symposium on usable privacy and security (p. 9). ACM .Kahanda, I., & Neville, J. (2009). Using transactional information to predict link strength in online social networks. In Proceedings of the third international conference on weblogs and social media (ICWSM).Lancichinetti, A., & Fortunato, S. (2009). Community detection algorithms: a comparative analysis. Physical Review E, 80, 056–117.Lancichinetti, A., Fortunato, S., Kertsz, J. (2009). Detecting the overlapping and hierarchical community structure in complex networks. New Journal of Physics, 11(3), 033–015.Lin, N., Ensel, W., Vaughn, J. (1981). Social resources and strength of ties: Structural factors in occupational status attainment. American Sociological Review, 393–405.Lipford, H., Besmer, A., Watson, J. (2008). Understanding privacy settings in facebook with an audience view. In Proceedings of the 1st conference on usability, psychology, and security (pp. 1–8). Berkeley: USENIX Association.Liu, G., Wang, Y., Orgun, M. (2010). Optimal social trust path selection in complex social networks. In Proceedings of the 24th AAAI conference on artificial intelligence (pp. 139–1398). AAAI.Matsuo, Y., Mori, J., Hamasaki, M., Nishimura, T., Takeda, H., Hasida, K., Ishizuka, M. (2007). Polyphonet: an advanced social network extraction system from the web. Web Semantics: Science, Services and Agents on the World Wide Web, 5(4), 262–278. World Wide Web Conference 2006 Semantic Web Track.Murukannaiah, P., & Singh, M. (2011). Platys social: relating shared places and private social circles. Internet Computing IEEE, 99, 1–1.Quercia, D., Lambiotte, R., Kosinski, M., Stillwell, D., Crowcroft, J. (2012). The personality of popular facebook users. In Proceedings of the ACM 2012 conference on computer supported cooperative work (CSCW’12).Rosvall, M., & Bergstrom, C. (2008). Maps of random walks on complex networks reveal community structure. Proceedings of the National Academy of Sciences, 105(4), 1118–1123.Sharma, G., Qiang, Y., Wenjun, S., Qi, L. (2013). Communication in virtual world: Second life and business opportunities. Information Systems Frontiers, 15(4), 677–694.Shen, K., Song, L., Yang, X., Zhang, W. (2010). A hierarchical diffusion algorithm for community detection in social networks. In 2010 international conference on cyber-enabled distributed computing and knowledge discovery (CyberC) (pp. 276–283). IEEE.Sierra, C., & Debenham, J. (2007). The LOGIC negotiation model. In AAMAS ’07: proceedings of the 6th international joint conference on autonomous agents and multiagent systems (pp. 1–8). ACM.Staddon, J., Huffaker, D., Brown, L., Sedley, A. (2012). Are privacy concerns a turn-off?: engagement and privacy in social networks. In Proceedings of the eighth symposium on usable privacy and security (p. 10). ACM.Strater, K., & Lipford, H.R. (2008). Strategies and struggles with privacy in an online social networking community. In Proceedings of the 22nd British HCI group annual conference on people and computers: culture, creativity, interaction, BCS-HCI ’08 (Vol. 1, pp. 111–119). Swinton: British Computer Society.Wellman, B., & Wortley, S. (1990). Different strokes from different folks: Community ties and social support. American Journal of Sociology, 558–588.Wiese, J., Kelley, P., Cranor, L., Dabbish, L., Hong, J., Zimmerman, J. (2011). Are you close with me? are you nearby? investigating social groups, closeness, and willingness to share. In Proceedings of the 13th international conference on Ubiquitous computing (pp. 197–206). ACM.Xiang, R., Neville, J., Rogati, M. (2010). Modeling relationship strength in online social networks. In Proceedings of the 19th international conference on World wide web (pp. 981–990). ACM

Cav3.2 calcium channel interactions with the epithelial sodium channel ENaC

Abstract This study describes the functional interaction between Cav3.2 calcium channels and the Epithelial Sodium Channel (ENaC). β-ENaC subunits showed overlapping expression with endogenous Cav3.2 calcium channels in the thalamus and hypothalamus as detected by immunostaining. Moreover, β- and γ-ENaC subunits could be co-immunoprecipitated with Cav3.2 calcium channels from brain lysates, dorsal horn and lumbar dorsal root ganglia. Mutation of a cluster of lysines present in the intracellular N-terminus region of β-ENaC (K4R/ K5R/ K9R/ K16R/ K23R) reduced interactions with Cav3.2 calcium channels. Αβγ-ENaC channels enhanced Cav3.2 calcium channel trafficking to the plasma membrane in tsA-201 cells. This effect was reciprocal such that Cav3.2 channel expression also enhanced β-ENaC trafficking to the cell surface. T-type current density was increased when fully assembled αβγ-ENaC channels were transiently expressed in CAD cells, a neuronal derived cell line. Altogether, these findings reveal ENaC as an interactor and potential regulator of Cav3.2 calcium channels expressed in neuronal tissues

IND-Enabling Studies for a Clinical Trial to Genetically Program a Persistent Cancer-Targeted Immune System

PURPOSE: To improve persistence of adoptively transferred T-cell receptor (TCR)-engineered T cells and durable clinical responses, we designed a clinical trial to transplant genetically-modified hematopoietic stem cells (HSCs) together with adoptive cell transfer of T cells both engineered to express an NY-ESO-1 TCR. Here, we report the preclinical studies performed to enable an investigational new drug (IND) application. EXPERIMENTAL DESIGN: HSCs transduced with a lentiviral vector expressing NY-ESO-1 TCR and the PET reporter/suicide gene HSV1-sr39TK and T cells transduced with a retroviral vector expressing NY-ESO-1 TCR were coadministered to myelodepleted HLA-A2/Kb mice within a formal Good Laboratory Practice (GLP)-compliant study to demonstrate safety, persistence, and HSC differentiation into all blood lineages. Non-GLP experiments included assessment of transgene immunogenicity and in vitro viral insertion safety studies. Furthermore, Good Manufacturing Practice (GMP)-compliant cell production qualification runs were performed to establish the manufacturing protocols for clinical use. RESULTS: TCR genetically modified and ex vivo-cultured HSCs differentiated into all blood subsets in vivo after HSC transplantation, and coadministration of TCR-transduced T cells did not result in increased toxicity. The expression of NY-ESO-1 TCR and sr39TK transgenes did not have a detrimental effect on gene-modified HSC's differentiation to all blood cell lineages. There was no evidence of genotoxicity induced by the lentiviral vector. GMP batches of clinical-grade transgenic cells produced during qualification runs had adequate stability and functionality. CONCLUSIONS: Coadministration of HSCs and T cells expressing an NY-ESO-1 TCR is safe in preclinical models. The results presented in this article led to the FDA approval of IND 17471

Short- and Long-Term Prognosis of Patients With Takotsubo Syndrome Based on Different Triggers: Importance of the Physical Nature

Background Takotsubo syndrome (TTS) is an acute reversible heart condition initially believed to represent a benign pathology attributable to its self-limiting clinical course; however, little is known about its prognosis based on different triggers. This study compared short- and long-term outcomes between TTS based on different triggers, focusing on various physical triggering events. Methods and Results We analyzed patients with a definitive TTS diagnosis recruited for the Spanish National Registry on TTS (RETAKO [Registry on Takotsubo Syndrome]). Short- and long-term outcomes were compared between different groups according to triggering factors. A total of 939 patients were included. An emotional trigger was detected in 340 patients (36.2%), a physical trigger in 293 patients (31.2%), and none could be identified in 306 patients (32.6%). The main physical triggers observed were infections (30.7%), followed by surgical procedures (22.5%), physical activities (18.4%), episodes of severe hypoxia (18.4%), and neurological events (9.9%). TTS triggered by physical factors showed higher mortality in the short and long term, and within this group, patients whose physical trigger was hypoxia were those who had a worse prognosis, in addition to being triggered by physical factors, including age >70 years, diabetes mellitus, left ventricular eyection fraction <30% and shock on admission, and increased long-term mortality risk. Conclusions TTS triggered by physical factors could present a worse prognosis in terms of mortality. Under the TTS label, there could be as yet undiscovered very different clinical profiles, whose differentiation could lead to individual better management, and therefore the perception of TTS as having a benign prognosis should be generally ruled out

Harmonized-Multinational qEEG Norms (HarMNqEEG)

This paper extends the frequency domain quantitative electroencephalography (qEEG) methods pursuing higher sensitivity to detect Brain Developmental Disorders. Prior qEEG work lacked integration of cross-spectral information omitting important functional connectivity descriptors. Lack of geographical diversity precluded accounting for site-specific variance, increasing qEEG nuisance variance. We ameliorate these weaknesses. i) Create lifespan Riemannian multinational qEEG norms for cross-spectral tensors. These norms result from the HarMNqEEG project fostered by the Global Brain Consortium. We calculate the norms with data from 9 countries, 12 devices, and 14 studies, including 1564 subjects. Instead of raw data, only anonymized metadata and EEG cross-spectral tensors were shared. After visual and automatic quality control, developmental equations for the mean and standard deviation of qEEG traditional and Riemannian DPs were calculated using additive mixed-effects models. We demonstrate qEEG "batch effects" and provide methods to calculate harmonized z-scores. ii) We also show that the multinational harmonized Riemannian norms produce z-scores with increased diagnostic accuracy to predict brain dysfunction at school-age produced by malnutrition only in the first year of life. iii) We offer open code and data to calculate different individual z-scores from the HarMNqEEG dataset. These results contribute to developing bias-free, low-cost neuroimaging technologies applicable in various health settings

Reversal of SARS-CoV2-Induced Hypoxia by Nebulized Sodium Ibuprofenate in a Compassionate Use Program

Introduction: Sodium ibuprofenate in hypertonic saline (NaIHS) administered directly to the lungs by nebulization and inhalation has antibacterial and anti-inflammatory effects, with the potential to deliver these benefits to hypoxic patients. We describe a compassionate use program that offered this therapy to hospitalized COVID-19 patients. Methods: NaIHS (50 mg ibuprofen, tid) was provided in addition to standard of care (SOC) to hospitalized COVID-19 patients until oxygen saturation levels of > 94% were achieved on ambient air. Patients wore a containment hood to diminish aerosolization. Outcome data from participating patients treated at multiple hospitals in Argentina between April 4 and October 31, 2020, are summarized. Results were compared with a retrospective contemporaneous control (CC) group of hospitalized COVID-19 patients with SOC alone during the same time frame from a subset of participating hospitals from Córdoba and Buenos Aires. Results: The evolution of 383 patients treated with SOC + NaIHS [56 on mechanical ventilation (MV) at baseline] and 195 CC (21 on MV at baseline) are summarized. At baseline, NaIHS-treated patients had basal oxygen saturation of 90.7 ± 0.2% (74.3% were on supplemental oxygen at baseline) and a basal respiratory rate of 22.7 ± 0.3 breath/min. In the CC group, basal oxygen saturation was 92.6 ± 0.4% (52.1% were on oxygen supplementation at baseline) and respiratory rate was 19.3 ± 0.3 breath/min. Despite greater pulmonary compromise at baseline in the NaIHS-treated group, the length of treatment (LOT) was 9.1 ± 0.2 gs with an average length of stay (ALOS) of 11.5 ± 0.3 days, in comparison with an ALOS of 13.3 ± 0.9 days in the CC group. In patients on MV who received NaIHS, the ALOS was lower than in the CC group. In both NaIHS-treated groups, a rapid reversal of deterioration in oxygenation and NEWS2 scores was observed acutely after initiation of NaIHS therapy. No serious adverse events were considered related to ibuprofen therapy. Mortality was lower in both NaIHS groups compared with CC groups. Conclusions: Treatment of COVID-19 pneumonitis with inhalational nebulized NaIHS was associated with rapid improvement in hypoxia and vital signs, with no serious adverse events attributed to therapy. Nebulized NaIHS s worthy of further study in randomized, placebo-controlled trials (ClinicalTrials.gov: NCT04382768).Fil: Salva, Oscar. Clínica Independencia; ArgentinaFil: Doreski, Pablo A.. Fundación Respirar; ArgentinaFil: Giler, Celia S.. Clínica Independencia; ArgentinaFil: Quinodoz, Dario C.. Sanatorio de la Cañada; ArgentinaFil: Guzmán, Lucia G.. Sanatorio de la Cañada; ArgentinaFil: Muñoz, Sonia Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Carrillo, Mariana Norma del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Porta, Daniela Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Ambasch, Germán. Sanatorio Privado Mayo; ArgentinaFil: Coscia, Esteban. Sanatorio Privado Mayo; ArgentinaFil: Tambini Diaz, Jorge L.. Sanatorio Privado Mayo; ArgentinaFil: Bueno, Germán D.. Sanatorio Privado Mayo; ArgentinaFil: Fandi, Jorge O.. Clínica Independencia; ArgentinaFil: Maldonado, Miriam A.. Sanatorio San Roque; ArgentinaFil: Peña Chiappero, Leandro E.. Sanatori San Roque; ArgentinaFil: Fournier, Fernando. Clínica Francesa; ArgentinaFil: Pérez, Hernán A.. Sanatorio Alive; Argentina. University of Maryland; Estados UnidosFil: Quiroga, Mauro A.. Instituto Modelo de Cardiología; ArgentinaFil: Sala Mercado, Javier Agustin. Instituto Modelo de Cardiología; ArgentinaFil: Martínez Picco, Carlos. Clínica del Sol; ArgentinaFil: Beltrán, Marcelo Alejandro. Hospital Dr. Alberto Duhau; ArgentinaFil: Castillo Argañarás, Luis Fernando. Hospital Dr. Alberto Duhau; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ríos, Nicolás Martínez. Quimica Luar Srl; ArgentinaFil: Kalayan, Galia I.. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; ArgentinaFil: Beltramo, Dante Miguel. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Garcia, Nestor Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; Argentin

Angular resolution at map level in the QUBIC instrument

Desde su descubrimiento en los años 1960, el fondo cósmico de microondas (CMB, por sus siglas en ingles) se ha convertido en una importante herramienta observacional para entender la física del universo temprano. El parámetro r, definido como la amplitud de las perturbaciones tensoriales relativas a las escalares, está acotado actualmente al rango r < 0.056. QUBIC es un instrumento terrestre diseñado para buscar señales muy débiles de los modos B en las anisotropías de la polarización a escalas angulares intermedias (l ∼ 30 − 200). Para lograr este objetivo, QUBIC combina dos técnicas muy usadas en la comunidad CMB: interferometría y bolometría. En este trabajo calculamos la resolución angular de una simulación end-to-end con dos métodos independientes: Fit y Sigma. Concluimos que la reconstrucción que realiza el software es apropiada ya que la resolución medida con ambos métodos calibrados coincide con los valores teóricos de la resolución esperada.Since its discovery in the 1960s, the cosmic microwave background (CMB) radiation has become a very important observational tool to understand the physics of the early universe. The parameter r, defined as the relative amplitude of tensor to scalar perturbations, is currently constrained to the range r < 0.056. QUBIC is a ground-based instrument designed to search for very weak B-mode signals in polarization anisotropies at intermediate angular scales (l ∼ 30 − 200). To achieve this goal, QUBIC combines two widely used techniques in the CMB community: interferometry and bolometry. In this work, we compute the angular resolution for an end-to-end simulation using two independent methods: Fit and Sigma. We conclude that the reconstruction performed by the software is appropriate since the resolution measured with both calibrated methods coincides with the theoretical value of the expected resolution.Fil: Gamboa Lerena, Martín Miguel. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Scoccola, Claudia Graciela. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ade, P.. Cardiff University; Reino UnidoFil: Alberro, José Gabriel. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas; ArgentinaFil: Almela, Daniel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Arnaldi, L. H.. Comisión Nacional de Energía Atómica; ArgentinaFil: Bonaparte, J.. Comisión Nacional de Energía Atómica; ArgentinaFil: Bottani, A.. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas; ArgentinaFil: Cobos Cerutti, Agustin Cleto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Duca, Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Etchegoyen, Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Fasciszewski, A.. Comisión Nacional de Energía Atómica; ArgentinaFil: Ferreyro, Luciano Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Fracchia, D.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Garcia, Beatriz Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: García Redondo, Manuel Elías. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Gomez Berisso, Mariano. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: González, Manuel. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Harari, Diego Dario. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kristukat, C.. Comisión Nacional de Energía Atómica; ArgentinaFil: Mundo, Luis Mariano. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas; ArgentinaFil: Pastoriza, Hernan. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Platino, Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Ringegni, P.. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas; ArgentinaFil: Romero, Gustavo Esteban. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Salum, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Supanitsky, Alberto Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Wicek, F.. Institut National de Physique Nucléaire et de Physique des Particules; FranciaFil: Zannoni, M.. Istituto Nazionale Di Fisica Nucleare; ItaliaFil: Zullo, A.. Istituto Nazionale Di Fisica Nucleare; ItaliaReunión Anual de la Asociación Argentina de AstronomíaViedmaArgentinaUniversidad Nacional de Río NegroInstituto Argentino de Radioastronomí

H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells

In differentiated cells, aging is associated with hypermethylation of DNA regions enriched in repressive histone post-translational modifications. However, the chromatin marks associated with changes in DNA methylation in adult stem cells during lifetime are still largely unknown. Here, DNA methylation profiling of mesenchymal stem cells (MSCs) obtained from individuals aged 2 to 92 yr identified 18,735 hypermethylated and 45,407 hypomethylated CpG sites associated with aging. As in differentiated cells, hypermethylated sequences were enriched in chromatin repressive marks. Most importantly, hypomethylated CpG sites were strongly enriched in the active chromatin mark H3K4me1 in stem and differentiated cells, suggesting this is a cell type–independent chromatin signature of DNA hypomethylation during aging. Analysis of scedasticity showed that interindividual variability of DNA methylation increased during aging in MSCs and differentiated cells, providing a new avenue for the identification of DNA methylation changes over time. DNA methylation profiling of genetically identical individuals showed that both the tendency of DNA methylation changes and scedasticity depended on nongenetic as well as genetic factors. Our results indicate that the dynamics of DNA methylation during aging depend on a complex mixture of factors that include the DNA sequence, cell type, and chromatin context involved and that, depending on the locus, the changes can be modulated by genetic and/or external factors