https://repositorio.fleni.org.ar/xmlui/handle/123456789/49 2026-07-26T00:01:34Z 2026-07-26T00:01:34Z Cukier, Sebastián H. Maglio, Ana Berman, Jonathan Arduini, Marco Barrios, Natalia Ngue, Maranada Montiel, Cecilia Ferrea, Mónica Gutson, Karina Zieba, Emilio Menassé, Marcela Grodberg, David https://repositorio.fleni.org.ar/xmlui/handle/123456789/1530 2026-07-23T17:09:28Z 2026-01-10T00:00:00Z

Validación del examen del estado mental en autismo en español : sensibilidad y especificidad en una muestra clínica argentina Cukier, Sebastián H.; Maglio, Ana; Berman, Jonathan; Arduini, Marco; Barrios, Natalia; Ngue, Maranada; Montiel, Cecilia; Ferrea, Mónica; Gutson, Karina; Zieba, Emilio; Menassé, Marcela; Grodberg, David Introducción: El examen del estado mental en autismo (AMSE, por sus siglas en inglés) es un instrumento breve completado por el clínico que estructura la observación y documentación de los signos y características socio-comunicativas y conductuales del autismo. En su versión original en inglés demostró alta precisión en la identificación del trastorno del espectro autista (TEA). El presente estudio explora la sensibilidad y especificidad de una versión de AMSE en lengua española en una muestra argentina de 313 sujetos, frente al diagnóstico de consenso clínico utilizando los criterios del DSM-5. Materiales y métodos: Se calcularon los valores de corte mediante el análisis de la curva ROC (Característica Operativa del Receptor por sus siglas en inglés: Receiver Operating Characteristic), identificando la sensibilidad, especificidad, valor predictivo positivo (VPP) y valor predictivo negativo (VPN) correspondientes. La homogeneidad interna de los ítems fue evaluada a través del coeficiente alfa de Cronbach. Asimismo, se calculó el coeficiente Kappa de Cohen para estimar la confiabilidad interevaluador. Resultados: Los hallazgos indican una sensibilidad optimizada del 90,71 % y una especificidad del 92,17 % para esta muestra de 313 pacientes. AMSE mostró una consistencia interna aceptable de .75 y una alta confiabilidad entre evaluadores (K = .97). Discusión y conclusiones: AMSE se perfila como una herramienta prometedora para la evaluación diagnóstica de TEA en niños, adolescentes y adultos en riesgo, destacándose por su alta utilidad clínica. Su aplicación es especialmente relevante en regiones como América Latina, donde el acceso a la capacitación y uso de las escalas que son estándar de oro es limitado. Estos resultados respaldan el uso de AMSE como una herramienta diagnóstica breve, confiable y culturalmente adaptada para apoyar el diagnóstico clínico de autismo en contextos de habla hispana con recursos limitados.

2026-01-10T00:00:00Z Budnik, Nicolás Canedo, Lucía Morellato, Agustín E. Cuenca, Marina B. Garmendia, Martina Senin, Sergio Romano, Sebastián A. Andrysik, Zdenek Videla Richardson, Guillermo Agustín Graner, Michael W. Kobayashi, Ken Zhou, Yilong Wiese, Meike Akhtar, Asifa Espinosa, Joaquín M. Perez-Castro, Carolina https://repositorio.fleni.org.ar/xmlui/handle/123456789/1521 2026-07-02T18:17:01Z 2026-03-05T00:00:00Z

Nucleoli-localized KANSL2 as an epigenetic regulator of ribosome biogenesis in glioblastoma cells Budnik, Nicolás; Canedo, Lucía; Morellato, Agustín E.; Cuenca, Marina B.; Garmendia, Martina; Senin, Sergio; Romano, Sebastián A.; Andrysik, Zdenek; Videla Richardson, Guillermo Agustín; Graner, Michael W.; Kobayashi, Ken; Zhou, Yilong; Wiese, Meike; Akhtar, Asifa; Espinosa, Joaquín M.; Perez-Castro, Carolina KANSL2 is a subunit of the non-specific lethal (NSL) chromatin-modifying complex associated with glioblastoma (GBM) progression, but the intrinsic role of KANSL2 in GBM cells is poorly understood. By analyzing TCGA-GBM and GTEx datasets, we found that KANSL2 is upregulated in GBM and positively correlates with genes involved in ribosome biogenesis. Immunofluorescence and cell cycle analyses reveal a dynamic nuclear distribution, with KANSL2 becoming enriched in nucleoli mainly during G1/early S and G2 phases. Overexpression of KANSL2 increases 45S pre-rRNA and 28S rRNA levels, whereas its silencing reduces rRNA expression and histone H4 acetylation at lysines 5 and 8 within rDNA promoters. RNA-seq of patient-derived GBM spheroids confirms a global downregulation of ribosome biogenesis genes upon silencing of KANSL2. Together, these findings identify KANSL2 as a nuclear factor that transiently associates with nucleoli to promote rRNA transcription and ribosome biogenesis, supporting the biosynthetic and proliferative capacity of glioblastoma cells.

2026-03-05T00:00:00Z Sevlever, Federico Waisman, Ariel Miriuka, Santiago Ventura, Alejandra C. https://repositorio.fleni.org.ar/xmlui/handle/123456789/1498 2026-05-27T13:56:09Z 2025-11-21T00:00:00Z

Persistent memory in network topologies following temporary stimuli Sevlever, Federico; Waisman, Ariel; Miriuka, Santiago; Ventura, Alejandra C. Molecular memory in signaling and gene regulatory networks shapes how cells respond to transient inputs. Here, we present a mathematical framework to quantify memory as changes in system state after temporary stimulation. Using computational models, we show that circuits with positive feedback loops, particularly those enabling bistability, sustain long-term memory, while certain negative feedbacks can erase it. We further identify minimal network motifs that reliably confer memory, revealing symmetry between activating and inactivating mechanisms. In addition, oscillatory circuits can encode memory even without positive feedback, storing information in the phase of their oscillations. Applying this approach to mouse embryonic stem cells exposed to transient differentiation cues, we find that different genes display distinct degrees of memory retention, with some reflecting partial reversion and others indicating commitment to differentiation. This framework provides a unified way to compare memory across systems and highlights how circuit architecture influences information storage in biology.

2025-11-21T00:00:00Z Castañeda, Sheila Amín, Guadalupe Freiberger, María Inés Zabalegui, Federico Renes, Sol Fernández Gamba, Ágata Rosa, Alberto Luis Cejas, Claudia Patricia Pastor Rueda, José Manuel Waisman, Ariel Ferreiro, Diego Sevlever, Gustavo Emilio Miriuka, Santiago Moro, Lucía Natalia https://repositorio.fleni.org.ar/xmlui/handle/123456789/1492 2026-05-19T14:39:14Z 2025-12-31T00:00:00Z

Novel in-frame variant in DES (p.Glu353dup) causes myofibrillar myopathy: clinical, in silico and functional studies Castañeda, Sheila; Amín, Guadalupe; Freiberger, María Inés; Zabalegui, Federico; Renes, Sol; Fernández Gamba, Ágata; Rosa, Alberto Luis; Cejas, Claudia Patricia; Pastor Rueda, José Manuel; Waisman, Ariel; Ferreiro, Diego; Sevlever, Gustavo Emilio; Miriuka, Santiago; Moro, Lucía Natalia Background: Desmin (DES) is a major intermediate filament protein involved in the structural integrity and function of striated muscles. Pathogenic mutations in DES are predominantly missense variants, causing isolated cardiomyopathy and combinations of myopathy and cardiomyopathy. In-frame insertions are very rare and usually classified as variants of uncertain significance or likely pathogenic due to limited predictive and/or experimental evidence. Methods: This study describes a novel heterozygous in-frame insertion in exon 6 of DES (RefSeq NM_001927.4:c.1059_1061dup) identified in an Argentine family with myofibrillar myopathy (MFM). This mutation results in the duplication of a glutamic acid residue at position 353 (NP_001918.3:p.(Glu353dup)), in the 2B subdomain of the central rod domain. Clinical, computational and functional analyses were performed to study the pathogenicity of this variant. Results: Clinically, the index patient exhibited hallmark MFM features, including progressive muscle weakness, atrophy and fatty muscle replacement. In silico analyses of molecular dynamics revealed that p.Glu353dup alters DES dimer assembly by stabilising an aberrant coiled-coil conformation, a mechanism not previously proposed for DES mutations. Functional studies in HEK293T cells and C2C12 myocytes suggested that the p.Glu353dup variant induces aberrant DES aggregation, confirming its detrimental effect on filament organisation. Conclusion: These findings are consistent with the idea that p.Glu353dup is a pathogenic variant, supported by clinical studies, in silico protein modelling and functional evidence, highlighting the impact of in-frame insertions on DES filament homeostasis. By providing computational and experimental evidence, this study expands our understanding of desminopathies and offers new perspectives for pathogenicity assessment of uncertain DES variants.

2025-12-31T00:00:00Z