Populus MYC2 orchestrates root transcriptional reprogramming of defence pathway to impair Laccaria bicolor ectomycorrhizal development.

The jasmonic acid (JA) signalling pathway plays an important role in the establishment of the ectomycorrhizal symbiosis. The Laccaria bicolor effector MiSSP7 stabilizes JA corepressor JAZ6, thereby inhibiting the activity of Populus MYC2 transcription factors. Although the role of MYC2 in orchestrating plant defences against pathogens is well established, its exact contribution to ECM symbiosis remains unclear. This information is crucial for understanding the balance between plant immunity and symbiotic relationships. Transgenic poplars overexpressing or silencing for the two paralogues of MYC2 transcription factor (MYC2s) were produced, and their ability to establish ectomycorrhiza was assessed. Transcriptomics and DNA affinity purification sequencing were performed. MYC2s overexpression led to a decrease in fungal colonization, whereas its silencing increased it. The enrichment of terpene synthase genes in the MYC2-regulated gene set suggests a complex interplay between the host monoterpenes and fungal growth. Several root monoterpenes have been identified as inhibitors of fungal growth and ECM symbiosis. Our results highlight the significance of poplar MYC2s and terpenes in mutualistic symbiosis by controlling root fungal colonization. We identified poplar genes which direct or indirect control by MYC2 is required for ECM establishment. These findings deepen our understanding of the molecular mechanisms underlying ECM symbiosis.

Non-canonical antigens are the largest fraction of peptides presented by MHC class I in mismatch repair deficient murine colorectal cancer.

BACKGROUND: Immunotherapy based on checkpoint inhibitors is highly effective in mismatch repair deficient (MMRd) colorectal cancer (CRC). These tumors carry a high number of mutations, which are predicted to translate into a wide array of neoepitopes; however, a systematic classification of the neoantigen repertoire in MMRd CRC is lacking. Mass spectrometry peptidomics has demonstrated the existence of MHC class I associated peptides (MAPs) originating from non-coding DNA regions. Based on these premises we investigated DNA genomic regions responsible for generating MMRd-induced peptides. METHODS: We exploited mouse CRC models in which the MMR gene Mlh1 was genetically inactivated. Isogenic cell lines CT26 Mlh1+/+ and Mlh1-/- were inoculated in immunocompromised and immunocompetent mice. Whole genome and RNA sequencing data were generated from samples obtained before and after injection in murine hosts. First, peptide databases were built from transcriptomes of isogenic cell lines. We then compiled a database of peptides lost after tumor cells injection in immunocompetent mice, likely due to immune editing. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and matched next-generation sequencing databases were employed to identify the DNA regions from which the immune-targeted MAPs originated. Finally, we adopted in vitro T cell assays to verify whether MAP-specific T cells were part of the in vivo immune response against Mlh1-/- cells. RESULTS: Whole genome sequencing analyses revealed an unbalanced distribution of immune edited alterations across the genome in Mlh1-/- cells grown in immunocompetent mice. Specifically, untranslated (UTR) and coding regions exhibited the largest fraction of mutations leading to highly immunogenic peptides. Moreover, the integrated computational and LC-MS/MS analyses revealed that MAPs originate mainly from atypical translational events in both Mlh1+/+ and Mlh1-/- tumor cells. In addition, mutated MAPs-derived from UTRs and out-of-frame translation of coding regions-were highly enriched in Mlh1-/- cells. The MAPs trigger T-cell activation in mice primed with Mlh1-/- cells. CONCLUSIONS: Our results suggest that-in comparison to MMR proficient CRC-MMRd tumors generate a significantly higher number of non-canonical mutated peptides able to elicit T cell responses. These results reveal the importance of evaluating the diversity of neoepitope repertoire in MMRd tumors.

Programa de infecciones respiratorias agudas en la provincia de Buenos Aires: resultados en 2019 / Program of acute respiratory infections in Buenos Aires province: results in 2019

RESUMEN INTRODUCCIÓN Desde 2002 el Ministerio de Salud de la Provincia de Buenos Aires realiza acciones para disminuir la mortalidad infantil y las internaciones innecesarias por infecciones respiratorias agudas (IRA). A 17 años de la implementación del respectivo Programa, se analizan los datos del Programa en 2019 con el objetivo de evaluar sus resultados. MÉTODOS Se reunieron los datos registrados durante 2019 en toda la Provincia y se analizaron utilizando un software ad hoc. RESULTADOS Se analizaron 161 101 episodios de IRA bajas atendidos entre junio y agosto de 2019, con los siguientes resultados: resolución de 93,7% (97,3% en primer nivel de atención y 92% en segundo nivel; uso de inhalador de dosis medida (IDM) en 87,3%, de nebulizador en 7,4% y mixto en 5,3%; 12,5% en edad de 0-4 meses; 24,5% en 4-6; 22,1% en 7-11 y 40,8% en 12 o más; diagnóstico de síndrome bronquial obstructivo en 94,9%, de neumonía en 3,6% y de ambos en 1,5%; derivación a segundo nivel con uso de IDM en 5,2% y con uso de nebulizador en 8,2%; riesgo de enfermedad de base: 5,2%; madre menor de 17 años: 5,2%; madre con primaria incompleta: 13%; peso de nacimiento menor a 2500 g: 6,3%; fumador en la casa: 33,7%. DISCUSIÓN Hubo mayor resolución de casos en el primer nivel que en el segundo, menor número de internaciones con IDM que con nebulizador, y la sumatoria de riesgos se asoció a incremento de derivaciones y de gravedad.

ABSTRACT INTRODUCTION The Ministry of Health of the Province of Buenos Aires has been carrying out actions since 2002 with the objective of reducing infant mortality and unnecessary hospitalizations due to acute respiratory infections (ARI). Seventeen years after the implementation of the ARI program, an analysis of the 2019 data was performed. METHODS The strategy was focused on nursing and primary care level, including therapeutic test according to clinical score, bronchodilator in a metered-dose inhaler (MDI) and spacer, oxygen according to score, and records since 2004. RESULTS A total of 161,101 episodes of low ARI treated from June to August 2019 were analyzed, with the following results: resolution of 93.7% (97.3% in first level and 92.0% in second level); MDI use in 87.3%, nebulizer in 7.4% and mixed in 5.3%; 12.5% under 4 months of age, 24.5% in 4-6 months, 22.1% in 7-11 months, and 40.8% in 12 months or more; diagnosis of bronchial obstructive syndrome in 94.9%, of pneumonia in 3.6% and of both in 1.5%; referral to Second Level with use of MDI in 5.2% and with use of nebulizer in 8.2%; risk of underlying disease: 5.2%; mother under 17 years old: 5.2%; mother who has not completed elementary school: 13.0%; birth weight less than 2,500 g: 6.3%; smoker in the household: 33.7%. DISCUSSION There was a higher number of cases solved in the first than in the second level of care, lower number of hospitalizations with MDI than with nebulizer, and the sum of risks was associated with a greater number of referrals and greater severity.

Programa de infecciones respiratorias agudas en la provincia de Buenos Aires resultados 2019 / Program of acute respiratory infections in Buenos Aires province: results in 2019

Desde 2002 el Ministerio de Salud de la Provincia de Buenos Aires realiza acciones para disminuir la mortalidad infantil y las internaciones innecesarias por infecciones respiratorias agudas (IRA). A 17 años de la implementación del respectivo Programa, se analizan los datos del Programa en 2019 con el objetivo de evaluar sus resultados. MÉTODOS: Se reunieron los datos registrados durante 2019 en toda la Provincia y se analizaron utilizando un software ad hoc. RESULTADOS: Se analizaron 161 101 episodios de IRA bajas atendidos entre junio y agosto de 2019, con los siguientes resultados: resolución de 93,7% (97,3% en primer nivel de atención y 92% en segundo nivel; uso de inhalador de dosis medida (IDM) en 87,3%, de nebulizador en 7,4% y mixto en 5,3%; 12,5% en edad de 0-4 meses; 24,5% en 4-6; 22,1% en 7-11 y 40,8% en 12 o más; diagnóstico de síndrome bronquial obstructivo en 94,9%, de neumonía en 3,6% y de ambos en 1,5%; derivación a segundo nivel con uso de IDM en 5,2% y con uso de nebulizador en 8,2%; riesgo de enfermedad de base: 5,2%; madre menor de 17 años: 5,2%; madre con primaria incompleta: 13%; peso de nacimiento menor a 2500 g: 6,3%; fumador en la casa: 33,7%. DISCUSIÓN: Hubo mayor resolución de casos en el primer nivel que en el segundo, menor número de internaciones con IDM que con nebulizador, y la sumatoria de riesgos se asoció a incremento de derivaciones y de gravedad