A2ML1 and otitis media: novel variants, differential expression, and relevant pathways

A genetic basis for otitis media is established, however, the role of rare variants in disease etiology is largely unknown. Previously a duplication variant within A2ML1 was identified as a significant risk factor for otitis media in an indigenous Filipino population and in US children. In this report exome and Sanger sequencing was performed using DNA samples from the indigenous Filipino population, Filipino cochlear implantees, US probands, Finnish, and Pakistani families with otitis media. Sixteen novel, damaging A2ML1 variants identified in otitis media patients were rare or low-frequency in population-matched controls. In the indigenous population, both gingivitis and A2ML1 variants including the known duplication variant and the novel splice variant c.4061 + 1 G>C were independently associated with otitis media. Sequencing of salivary RNA samples from indigenous Filipinos demonstrated lower A2ML1 expression according to the carriage of A2ML1 variants. Sequencing of additional salivary RNA samples from US patients with otitis media revealed differentially expressed genes that are highly correlated with A2ML1 expression levels. In particular, RND3 is upregulated in both A2ML1 variant carriers and high-A2ML1 expressors. These findings support a role for A2ML1 in keratinocyte differentiation within the middle ear as part of otitis media pathology and the potential application of ROCK inhibition in otitis media

The VISCACHA survey: III. Star clusters counterpart of the Magellanic Bridge and Counter-Bridge in 8D

Context. The interactions between the Small and Large Magellanic Clouds (SMC and LMC) created the Magellanic Bridge; a stream of gas and stars pulled out of the SMC towards the LMC about 150 Myr ago. The tidal counterpart of this structure, which should include a trailing arm, has been predicted by models but no compelling observational evidence has confirmed the Counter-Bridge so far. Aims. The main goal of this work is to find the stellar counterpart of the Magellanic Bridge and Counter-Bridge. We use star clusters in the SMC outskirts as they provide a 6D phase-space vector, age, and metallicity which help characterise the outskirts of the SMC. Methods. Distances, ages, and photometric metallicities were derived from fitting isochrones to the colour-magnitude diagrams from the VISCACHA survey. Radial velocities and spectroscopic metallicities were derived from the spectroscopic follow-up using GMOS in the CaII triplet region. Results. Among the seven clusters analysed in this work, five belong to the Magellanic Bridge, one belongs to the Counter-Bridge, and the other belongs to the transition region. Conclusions. The existence of the tidal counterpart of the Magellanic Bridge is evidenced by star clusters. The stellar component of the Magellanic Bridge and Counter-Bridge are confirmed in the SMC outskirts. These results are an important constraint for models that seek to reconstruct the history of the orbit and interactions between the LMC and SMC as well as constrain their future interaction including with the Milky Way.Fil: Dias, B.. Universidad de Tarapacá; ChileFil: Angelo, M.S.. Centro Federal de Educação Tecnológica de Minas Gerais; BrasilFil: Oliveira, R.A.P.. Universidade de Sao Paulo; BrasilFil: Maia, F.. Universidade Federal do Rio de Janeiro; BrasilFil: Parisi, Maria Celeste. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; ArgentinaFil: de Bórtoli, Bruno Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Souza, S.O.. Universidade de Sao Paulo; BrasilFil: Katime Santrich, O.J.. Universidade Estadual de Santa Cruz; BrasilFil: Bassino, Lilia Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Barbuy, B.. Universidade de Sao Paulo; BrasilFil: Bica, E.. Universidade Federal do Rio Grande do Sul; BrasilFil: Geisler, D.. Universidad de La Serena; Chile. Universidad de Concepción; ChileFil: Kerber, L.. Universidade Estadual de Santa Cruz; BrasilFil: Pérez Villegas, A.. Universidade de Sao Paulo; Brasil. Universidad Nacional Autónoma de México; MéxicoFil: Quint, B.. Gemini Observatory; ChileFil: Sanmartim, D.. Las Campanas Observatory; ChileFil: Santos Jr., João F. C.. Universidade Federal de Minas Gerais; BrasilFil: Westera, P.. Universidade Federal Do Abc; Brasi