¿Cual es la función de las nucleoporinas AtSAR1 y AtSAR3 en la meiosis de " Arabidopsis thaliana"

El complejo del poro nuclear regula el transporte núcleo-citoplasmático. Existe una relación con la supresión de la resistencia auxinas cuando se alteran algunas nucleoporinas. Concretamente, mutaciones en AtSAR1/AtNUP160 (Suppressor of Auxin Resistance1) y AtSAR3/AtNUP96 suprimen el fenotipo característico de los mutantes Ataxr1 (Auxin Resistant1) como: pérdida de la dominancia apical y del gravitropismo de la raíz, reducción de la formación de raíces laterales, aumento de la longitud de la raíz primaria, reducción de la altura de la planta y de la fertilidad. AtAXR1 es una proteína implicada en la ruta de rubilación. Esta proteína es determinante en la degradación de la proteína Aux/IAA, represora de la expresión de genes de respuesta a auxinas. Además se ha demostrado fundamental durante el proceso de localización de los sobrecruzamientos en la meiosis de Arabidopsis. Los mutantes para las proteínas AtSAR presentaron un fenotipo pleiotrópico, manifestando diversos defectos en el desarrollo vegetativo y la fertilidad. El objetivo del presente trabajo fue caracterizar los mutantes Atsar1-4 y Atsar3-3 para determinar si las alteraciones en fertilidad son debidas a anomalías durante la división meiótica y conocer más sobre las funciones del complejo del poro nuclear

Synthetically induced Arabidopsis thaliana autotetraploids provide insights into the analysis of meiotic mutants with altered crossover frequency

Mutations affecting crossover (CO) frequency and distribution lead to the presence of univalents during meiosis, giving rise to aneuploid gametes and sterility. These mutations may have a different effect after chromosome doubling. The combination of altered ploidy and mutations could be potentially useful to gain new insights into the mechanisms and regulation of meiotic recombination; however, studies using autopolyploid meiotic mutants are scarce. Here, we have analyzed the cytogenetic consequences in colchicine-induced autotetraploids (colchiploids) from different Arabidopsis mutants with an altered CO frequency. We have found that there are three types of mutants: mutants in which chiasma frequency is doubled after chromosome duplication (zip4, mus81), as in the control; mutants in which polyploidy leads to a higher-than-expected increase in chiasma frequency (asy1, mer3, hei10, and mlh3); and mutants in which the rise in chiasma frequency produced by the presence of two extrachromosomal sets is less than doubled (msh5, fancm). In addition, the proportion of class I/class II COs varies after chromosome duplication in the control. The results obtained reveal the potential of colchiploid meiotic mutants for better understanding of the function of key proteins during plant meiosis. This is especially relevant considering that most crops are polyploids.Depto. de Genética, Fisiología y MicrobiologíaFac. de Ciencias BiológicasTRUEpu

Structural Maintenance of Chromosomes 5/6 Complex Is Necessary for Tetraploid Genome Stability in Arabidopsis thaliana

Polyploidization is a common phenomenon in the evolution of flowering plants. However, only a few genes controlling polyploid genome stability, fitness, and reproductive success are known. Here, we studied the effects of loss-of-function mutations in NSE2 and NSE4A subunits of the Structural Maintenance of Chromosomes 5/6 (SMC5/6) complex in autotetraploid Arabidopsis thaliana plants. The diploid nse2 and nse4a plants show partially reduced fertility and produce about 10% triploid offspring with two paternal and one maternal genome copies. In contrast, the autotetraploid nse2 and nse4a plants were almost sterile and produced hexaploid and aneuploid progeny with the extra genome copies or chromosomes coming from both parents. In addition, tetraploid mutants had more severe meiotic defects, possibly due to the presence of four homologous chromosomes instead of two. Overall, our study suggests that the SMC5/6 complex is an important player in the maintenance of tetraploid genome stability and that autotetraploid Arabidopsis plants have a generally higher frequency of but also higher tolerance for aneuploidy compared to diploids

Duplication and divergence: new insights into AXR1 and AXL functions in DNA repair and meiosis

Rubylation is a conserved regulatory pathway similar to ubiquitination and essential in the response to the plant hormone auxin. In Arabidopsis thaliana, AUXIN RESISTANT1 (AXR1) functions as the E1-ligase in the rubylation pathway. The gene AXR1-LIKE (AXL), generated by a relatively recent duplication event, can partially replace AXR1 in this pathway. We have analysed mutants defcient for both proteins and complementation lines (with the AXR1 promoter and either AXR1 or AXL coding sequences) to further study the extent of functional redundancy between both genes regarding two processes: meiosis and DNA repair. Here we report that whereas AXR1 is essential to ensure the obligatory chiasma, AXL seems to be dispensable during meiosis, although its absence slightly alters chiasma distribution. In addition, expression of key DNA repair and meiotic genes is altered when either AXR1 or AXL are absent. Furthermore, our results support a signifcant role for both genes in DNA repair that was not previously described. These fndings highlight that AXR1 and AXL show a functional divergence in relation to their involvement in homologous recombination, exemplifying a duplicate retention model in which one copy tends to have more sub-functions than its paralog

Natural variation identifies SNI1, the SMC5/6 component, as a modifier of meiotic crossover in Arabidopsis.

The frequency and distribution of meiotic crossovers are tightly controlled; however, variation in this process can be observed both within and between species. Using crosses of two natural Arabidopsis thaliana accessions, Col and Ler, we mapped a crossover modifier locus to semidominant polymorphisms in SUPPRESSOR OF NPR1-1 INDUCIBLE 1 (SNI1), which encodes a component of the SMC5/6 complex. The sni1 mutant exhibits a modified pattern of recombination across the genome with crossovers elevated in chromosome distal regions but reduced in pericentromeres. Mutations in SNI1 result in reduced crossover interference and can partially restore the fertility of a Class I crossover pathway mutant, which suggests that the protein affects noninterfering crossover repair. Therefore, we tested genetic interactions between SNI1 and both RECQ4 and FANCM DNA helicases, which showed that additional Class II crossovers observed in the sni1 mutant are FANCM independent. Furthermore, genetic analysis of other SMC5/6 mutants confirms the observations of crossover redistribution made for SNI1 The study reveals the importance of the SMC5/6 complex in ensuring the proper progress of meiotic recombination in plants

mHealth intervention to improve quality of life in patients with chronic diseases during the COVID-19 crisis in Paraguay: A study protocol for a randomized controlled trial

Background Patients with chronic disease represent an at-risk group in the face of the COVID-19 crisis as they need to regularly monitor their lifestyle and emotional management. Coping with the illness becomes a challenge due to supply problems and lack of access to health care facilities. It is expected these limitations, along with lockdown and social distancing measures, have affected the routine disease management of these patients, being more pronounced in low- and middle-income countries with a flawed health care system. Objectives The purpose of this study is to describe a protocol for a randomized controlled trial to test the efficacy of the Adhera® MejoraCare Digital Program, an mHealth intervention aimed at improving the quality of life of patients with chronic diseases during the COVID-19 outbreak in Paraguay. Method A two-arm randomized controlled trial will be carried out, with repeated measures (baseline, 1-month, 3-month, 6-month, and 12-month) under two conditions: Adhera® MejoraCare Digital Program or waiting list. The primary outcome is a change in the quality of life on the EuroQol 5-Dimensions 3-Levels Questionnaire (EQ-5D-3L). Other secondary outcomes, as the effect on anxiety and health empowerment, will be considered. All participants must be 18 years of age or older and meet the criteria for chronic disease. A total of 96 participants will be recruited (48 per arm). Conclusions It is expected that the Adhera® MejoraCare Digital Program will show significant improvements in quality of life and emotional distress compared to the waiting list condition. Additionally, it is hypothesized that this intervention will be positively evaluated by the participants in terms of usability and satisfaction. The findings will provide new insights into the viability and efficacy of mHealth solutions for chronic disease management in developing countries and in times of pandemic

Real-world effectiveness of caplacizumab vs the standard of care in immune thrombotic thrombocytopenic purpura

Immune thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy caused by anti-ADAMTS13 antibodies. Caplacizumab is approved for adults with an acute episode of iTTP in conjunction with plasma exchange (PEX) and immunosuppression. The objective of this study was to analyze and compare the safety and efficacy of caplacizumab vs the standard of care and assess the effect of the concomitant use of rituximab. A retrospective study from the Spanish TTP Registry of patients treated with caplacizumab vs those who did not receive it was conducted. A total of 155 patients with iTTP (77 caplacizumab, 78 no caplacizumab) were included. Patients initially treated with caplacizumab had fewer exacerbations (4.5% vs 20.5%; P <.05) and less refractoriness (4.5% vs 14.1%; P <.05) than those who were not treated. Time to clinical response was shorter when caplacizumab was used as initial treatment vs caplacizumab used after refractoriness or exacerbation. The multivariate analysis showed that its use in the first 3 days after PEX was associated with a lower number of PEX (odds ratio, 7.5; CI, 2.3-12.7; P <.05) and days of hospitalization (odds ratio, 11.2; CI, 5.6-16.9; P <.001) compared with standard therapy. There was no difference in time to clinical remission in patients treated with caplacizumab compared with the use of rituximab. No severe adverse event was described in the caplacizumab group. In summary, caplacizumab reduced exacerbations and refractoriness compared with standard of care regimens. When administered within the first 3 days after PEX, it also provided a faster clinical response, reducing hospitalization time and the need for PEX