Fine-mapping and evolutionary history of R-BPMV, a dominant resistance gene to Bean pod mottle virus in Phaseolus vulgaris L.

KEY MESSAGE: R-BPMV is located within a recently expanded TNL cluster in the Phaseolus genus with suppressed recombination and known for resistance to multiple pathogens including potyviruses controlled by the I gene. Bean pod mottle virus (BPMV) is a comovirus that infects common bean and legumes in general. BPMV is distributed throughout the world and is a major threat on soybean, a closely related species of common bean. In common bean, BAT93 was reported to carry the R-BPMV resistance gene conferring resistance to BPMV and linked with the I resistance gene. To fine map R-BPMV, 182 recombinant inbred lines (RILs) derived from the cross BAT93 × JaloEEP558 were genotyped with polymerase chain reaction (PCR)-based markers developed using genome assemblies from G19833 and BAT93, as well as BAT93 BAC clone sequences. Analysis of RILs carrying key recombination events positioned R-BPMV to a target region containing at least 16 TIR-NB-LRR (TNL) sequences in BAT93. Because the I cluster presents a suppression of recombination and a large number of repeated sequences, none of the 16 TNLs could be excluded as R-BPMV candidate gene. The evolutionary history of the TNLs for the I cluster were reconstructed using microsynteny and phylogenetic analyses within the legume family. A single I TNL was present in Medicago truncatula and lost in soybean, mirroring the absence of complete BPMV resistance in soybean. Amplification of TNLs in the I cluster predates the divergence of the Phaseolus species, in agreement with the emergence of R-BPMV before the separation of the common bean wild centers of diversity. This analysis provides PCR-based markers useful in marker-assisted selection (MAS) and laid the foundation for cloning of R-BPMV resistance gene in order to transfer the resistance into soybean.

Construction of a questionnaire to characterise environmental exposures in patients with systemic lupus erythematosus / Construcción de un cuestionario para caracterizar exposiciones ambientales en pacientes con lupus eritematoso sistémico

ABSTRACT Introduction: As the knowledge of systemic lupus erythematosus (SLE) advances, the need to characterise the burden of environmental exposure in patients becomes increasingly relevant. However, there is currently no tool validated to measure such exposure. For this reason, the objective of this work was the construction of a questionnaire-type tool, in order to detail the exposure to multiple environmental factors previously associated with SLE. Methods: The literature was reviewed to identify relevant environmental factors associated with SLE, and the first version of the questionnaire was constructed. After expert review and feedback, the questionnaire was consolidated and applied to 40 patients and 20 healthy controls. Finally, exploratory Rasch analysis was performed to determine the performance of the tool's response function. Results: The tool showed a favourable performance in the exploratory analysis of its psychometric properties. Additionally, it allowed the characterisation of 10 environmental factors and the differences in the frequencies of exposure between patients with SLE and healthy controls. A high co-occurrence of exposures was identified, as most of the patients had positive exposures to three or more factors simultaneously. Conclusion: A practical and easy-to-apply tool has been constructed, with a favourable performance in its psychometric properties. To our knowledge, this is the first tool in the Spanish language for the characterisation of multiple environmental exposures, and constructed explicitly for patients with SLE with a validation analysis. It enabled us to identify that most of the lupus patients were exposed to the sum of three or more environmental factors.

RESUMEN Introducción: Con el avance en el conocimiento del lupus eritematoso sistémico (LES), se hace relevante la necesidad de caracterizar la carga de la exposición ambiental en los pacientes. Sin embargo, en la actualidad no se dispone de un instrumento validado para medirlo. Por consiguiente, el objetivo de este trabajo fue la construcción de un instrumento tipo cuestionario, a fin de detallar la exposición a múltiples factores ambientales previamente asociados a LES. Métodos: Se llevó a cabo una revisión de la literatura para identificar los factores ambientales asociados a LES y se construyó la primera versión del cuestionario. El instrumento se consolidó luego de la revisión y retroalimentación por expertos y se aplicó a 40 pacientes y 20 participantes sanos. Finalmente, se hizo análisis de Rasch exploratorio para determinar el desempeño en la función de respuesta. Resultados: El instrumento mostró un desempeño favorable en sus propiedades psicométricas. Adicionalmente, permitió la caracterización de 10 factores ambientales y sus diferencias en las frecuencias de exposición entre pacientes con LES y participantes sanos. Se identificó una alta co-ocurrencia de exposiciones reflejada en que la mayoría de los pacientes mostró exposición a tres o más factores simultáneamente. Conclusión: Se construyó un instrumento práctico y de fácil aplicación, con un desempeño favorable en sus propiedades psicométricas. Este instrumento, que es el primero para la caracterización de múltiples exposiciones ambientales específicamente diseñado para pacientes con LES, validado y en idioma español, permitió identificar que la mayoría de los pacientes con lupus estuvieron expuestos a la sumatoria de tres o más factores ambientales.

Advances in the Development of Pharmacological Chaperones for the Mucopolysaccharidoses.

The mucopolysaccharidoses (MPS) are a group of 11 lysosomal storage diseases (LSDs) produced by mutations in the enzymes involved in the lysosomal catabolism of glycosaminoglycans. Most of the mutations affecting these enzymes may lead to changes in processing, folding, glycosylation, pH stability, protein aggregation, and defective transport to the lysosomes. It this sense, it has been proposed that the use of small molecules, called pharmacological chaperones (PCs), can restore the folding, trafficking, and biological activity of mutated enzymes. PCs have the advantages of wide tissue distribution, potential oral administration, lower production cost, and fewer issues of immunogenicity than enzyme replacement therapy. In this paper, we will review the advances in the identification and characterization of PCs for the MPS. These molecules have been described for MPS II, IVA, and IVB, showing a mutation-dependent enhancement of the mutated enzymes. Although the results show the potential of this strategy, further studies should focus in the development of disease-specific cellular models that allow a proper screening and evaluation of PCs. In addition, in vivo evaluation, both pre-clinical and clinical, should be performed, before they can become a real therapeutic strategy for the treatment of MPS patients.

Widening of posterior glottis through rotation of the arytenoid on its axis: Report of nine cases.

INTRODUCTION: Bilateral vocal folds' immobility is a challenge in laryngology. Multiple procedures have been proposed to improve breathing by statically enlarging the glottal airway, what also results in loss of voice and aspiration. We proposed a technique to enlarge the posterior glottis by rotating the arytenoids on its axis, imitating the function of the posterior cricoarytenoid muscle, with the objective of evaluating the results regarding decannulation, voice quality, and bronchoaspiration. METHODS: This study is a clinical case series of patients with bilateral vocal fold paralysis who underwent an arytenoid rotation surgery at a single tertiary university care institution between 2011 and 2017. Data were prospectively collected and was complemented with information from medical charts. Patients were assessed for decannulation, dyspnea, posterior glottic opening, quality of voice, and swallowing disorders. RESULTS: Nine patients were included in the study. Out of three patients who required tracheostomy, two were successfully decannulated. Six patients reported a significant improvement in their dyspnea, while four patients reported a worsening of their voice. The stroboscopy evidenced a posterior glottic opening of at least 7 mm in six patients. Eight patients had no aspiratory symptoms, and the acoustic analysis showed that only one patient has a normal voice. CONCLUSION: The arytenoid rotation on its axis by imitating the posterior cricoarytenoid muscle preserves the physiological functions of the larynx, which allows sufficient opening of the posterior glottis for breathing, and could alter in a lesser extent the anterior glottis to maintain a good quality of voice and swallowing.