RESUMEN
BACKGROUND: Microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are the two major antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). OBJECTIVES: To characterize a homogenous AAV cohort and to assess the impact of clinicopathological profiles and ANCA serotypes on clinical presentation and prognosis. Clinical differences in GPA patients according to ANCA serotype and the diagnostic yield for vasculitis of biopsies in different territories were also investigated. RESULTS: This retrospective study (2000-2021) included 152 patients with AAV (77 MPA/75 GPA). MPA patients (96.1% myeloperoxidase [MPO]-ANCA and 2.6% proteinase 3 [PR3]-ANCA) presented more often with weight loss, myalgia, renal involvement, interstitial lung disease (ILD), cutaneous purpura, and peripheral nerve involvement. Patients with GPA (44% PR3-ANCA, 33.3% MPO, and 22.7% negative/atypical ANCA) presented more commonly with ear, nose, and throat and eye/orbital manifestations, more relapses, and higher survival than patients with MPA. GPA was the only independent risk factor for relapse. Poor survival predictors were older age at diagnosis and peripheral nerve involvement. ANCA serotypes differentiated clinical features in a lesser degree than clinical phenotypes. A mean of 1.5 biopsies were performed in 93.4% of patients in different territories. Overall, vasculitis was identified in 80.3% (97.3% in MPA and 61.8% in GPA) of patients. CONCLUSIONS: The identification of GPA presentations associated with MPO-ANCA and awareness of risk factors for relapse and mortality are important to guide proper therapeutic strategies in AAV patients. Biopsies of different affected territories should be pursued in difficult-to-diagnose patients based on their significant diagnostic yield.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Granulomatosis con Poliangitis , Poliangitis Microscópica , Humanos , Granulomatosis con Poliangitis/diagnóstico , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/tratamiento farmacológico , Poliangitis Microscópica/diagnóstico , Poliangitis Microscópica/complicaciones , Anticuerpos Anticitoplasma de Neutrófilos/uso terapéutico , Estudios Retrospectivos , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Mieloblastina , RecurrenciaRESUMEN
Food insecurity has been associated with negative short, medium, and long-term health consequences, which are more detrimental for children and adolescents. These effects may depend on the coping strategies developed to deal with food shortages. The present research aimed at exploring coping strategies in food insecure households with children and adolescents in Uruguay, incorporating sociological theoretical insights from Bourdieu. A qualitative approach based on individual semi-structured interviews was used. A total of 40 interviews were conducted with adults who had parental responsibilities of children and adolescents and who received different types of food assistance, between July and December 2022, in four cities. Results showed that adults tend to develop a wide range of coping strategies aimed at: reducing food expenditure, increasing the availability of money for purchasing food, increasing food availability and/or rationing the food available in the household. Some of the strategies were implemented regardless of the severity of food insecurity, whereas others were characteristic of the moderate and severe levels of the construct. Evidence to support the mediation effect of coping strategies on health outcomes was found. Discourses suggested that lower accumulation of economic and cultural capital may be aligned with the adoption of less socially accepted mechanisms to access to food. Expressions of a specific habitus aimed at securing food were identified among participants with more deprivations. Taken together, the findings suggest that coping strategies may not be a universal or invariant sequence according to the severity of food insecurity and stress the importance of considering households' resources and local context for the development of strategies to improve access to food.
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Habilidades de Afrontamiento , Composición Familiar , Inseguridad Alimentaria , Investigación Cualitativa , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Asistencia Alimentaria , Renta , Factores Socioeconómicos , UruguayRESUMEN
Fibrosing interstitial lung diseases (ILDs) are characterized by the gradual and irreversible accumulation of scar tissue in the lung parenchyma. The role of the immune response in the pathogenesis of pulmonary fibrosis remains unclear. In recent years, substantial advancements have been made in our comprehension of the pathobiology driving fibrosing ILDs, particularly concerning various age-related cellular disturbances and immune mechanisms believed to contribute to an inadequate response to stress and increased susceptibility to lung fibrosis. Emerging studies emphasize cellular senescence as a key mechanism implicated in the pathobiology of age-related diseases, including pulmonary fibrosis. Cellular senescence, marked by antagonistic pleiotropy, and the complex interplay with immunity, are pivotal in comprehending many aspects of lung fibrosis. Here, we review progress in novel concepts in cellular senescence, its association with the dysregulation of the immune response, and the evidence underlining its detrimental role in fibrosing ILDs.
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Senescencia Celular , Enfermedades Pulmonares Intersticiales , Fibrosis Pulmonar , Humanos , Senescencia Celular/inmunología , Enfermedades Pulmonares Intersticiales/inmunología , Enfermedades Pulmonares Intersticiales/patología , Fibrosis Pulmonar/inmunología , Fibrosis Pulmonar/patología , Animales , Pulmón/inmunología , Pulmón/patología , InmunidadRESUMEN
BACKGROUND: The role of the immune system in the pathobiology of Idiopathic Pulmonary Fibrosis (IPF) is controversial. METHODS: To investigate it, we calculated immune signatures with Gene Set Variation Analysis (GSVA) and applied them to the lung transcriptome followed by unbiased cluster analysis of GSVA immune-enrichment scores, in 109 IPF patients from the Lung Tissue Research Consortium (LTRC). Results were validated experimentally using cell-based methods (flow cytometry) in lung tissue of IPF patients from the University of Pittsburgh (n = 26). Finally, differential gene expression and hypergeometric test were used to explore non-immune differences between clusters. RESULTS: We identified two clusters (C#1 and C#2) of IPF patients of similar size in the LTRC dataset. C#1 included 58 patients (53%) with enrichment in GSVA immune signatures, particularly cytotoxic and memory T cells signatures, whereas C#2 included 51 patients (47%) with an overall lower expression of GSVA immune signatures (results were validated by flow cytometry with similar unbiased clustering generation). Differential gene expression between clusters identified differences in cilium, epithelial and secretory cell genes, all of them showing an inverse correlation with the immune response signatures. Notably, both clusters showed distinct features despite clinical similarities. CONCLUSIONS: In end-stage IPF lung tissue, we identified two clusters of patients with very different levels of immune signatures and gene expression but with similar clinical characteristics. Weather these immune clusters differentiate diverse disease trajectories remains unexplored.
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Perfilación de la Expresión Génica , Fibrosis Pulmonar Idiopática , Humanos , Perfilación de la Expresión Génica/métodos , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/genética , Fibrosis Pulmonar Idiopática/metabolismo , Pulmón/metabolismo , TranscriptomaRESUMEN
Pulmonary hypertension (PH) is a common complication of chronic lung diseases, particularly in chronic obstructive pulmonary disease (COPD) and interstitial lung diseases (ILD) and especially in advanced disease. It is associated with greater mortality and worse clinical course. Given the high prevalence of some respiratory disorders and because lung parenchymal abnormalities might be present in other PH groups, the appropriate diagnosis of PH associated with respiratory disease represents a clinical challenge. Patients with chronic lung disease presenting symptoms that exceed those expected by the pulmonary disease should be further evaluated by echocardiography. Confirmatory right heart catheterization is indicated in candidates to surgical treatments, suspected severe PH potentially amenable with targeted therapy, and, in general, in those conditions where the result of the hemodynamic assessment will determine treatment options. The treatment of choice for these patients who are hypoxemic is long-term oxygen therapy and pulmonary rehabilitation to improve symptoms. Lung transplant is the only curative therapy and can be considered in appropriate cases. Conventional vasodilators or drugs approved for pulmonary arterial hypertension (PAH) are not recommended in patients with mild-to-moderate PH because they may impair gas exchange and their lack of efficacy shown in randomized controlled trials. Patients with severe PH (as defined by pulmonary vascular resistance >5 Wood units) should be referred to a center with expertise in PH and lung diseases and ideally included in randomized controlled trials. Targeted PAH therapy might be considered in this subset of patients, with careful monitoring of gas exchange. In patients with ILD, inhaled treprostinil has been shown to improve functional ability and to delay clinical worsening.
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Hipertensión Pulmonar , Enfermedades Pulmonares Intersticiales , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/terapia , Pronóstico , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/terapia , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/terapia , Ecocardiografía/efectos adversosRESUMEN
Exposing pigs to heat stress (HS) provokes higher death of intestinal cells, resulting in elevated endogenous intestinal losses (EIL) of amino acids (AA) and damage to intestinal epithelia. Arginine (Arg) is precursor for the synthesis of polyamines, which are involved in proliferation of intestinal cells and restoration of the intestinal epithelia. Thus the effect of adding L-Arg to diets for HS pigs on the EIL of AA was analyzed. Twelve pigs (23.1 ± 1.1 kg body weight) implanted with T-type cannulas at the end of ileum were individually housed and allowed 15-days for surgery recovery under thermoneutral (TN) conditions (22 ± 2 °C). Following, the pigs were randomly assigned to one of three treatments: TN pigs fed a semi-purified, corn starch-3% casein basal diet (TN-B); HS pigs with the basal diet (HS-B); HS pigs consuming the basal diet supplemented with 0.20% L-Arg (HS-Arg). The experiment consisted of two 9-day periods; each period included 7-days of adaptation to their respective diet, followed by a 2-day ileal digesta collection period. Digesta was collected during 12 consecutive hours each day. The pigs were fed twice a-day. Ambient temperature (AT) inside the TN and HS rooms ranged from 18.6 to 27.6 °C and from 29.5 to 40.7 °C, respectively. Body temperature followed a pattern similar to that of AT. The daily EIL of indispensable AA increased (P < 0.01) in the HS-B pigs compared to both the TN-B and the HS-Arg pigs, however, there was no EIL difference between the TN-B and the HS-Arg pigs (P > 0.05). Likewise, with the exception of serine, daily losses of endogenous dispensable AA in the HS-B pigs were higher (P < 0.01) in comparison with those of TN-B and HS-Arg pigs. In summary, HS exposure compared to TN conditions increases the loss of endogenous AA, but dietary supplementation with L-Arg helped to counteract the negative HS effect.
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Aminoácidos , Trastornos de Estrés por Calor , Animales , Aminoácidos/metabolismo , Alimentación Animal/análisis , Arginina/farmacología , Suplementos Dietéticos , Trastornos de Estrés por Calor/prevención & control , Trastornos de Estrés por Calor/veterinaria , Trastornos de Estrés por Calor/metabolismo , Respuesta al Choque Térmico , PorcinosRESUMEN
(1) The role of the immune response in the pathogenesis of idiopathic pulmonary fibrosis (IPF) remains controversial. We hypothesized that peripheral blood immune phenotypes will be different in IPF patients and may relate to the disease severity and progression. (2) Whole blood flow cytometry staining was performed at diagnosis in 32 IPF patients, and in 32 age- and smoking-matched healthy controls. Thirty-one IPF patients were followed up for one year and categorized as stable or progressors based on lung function, deterioration and/or death. At 18-60 months, immunophenotypes were characterized again. (3) The main results showed that: (1) compared to matched controls, at diagnosis, patients with IPF showed more neutrophils, CD8+HLA-DR+ and CD8+CD28- T cells, and fewer B lymphocytes and naïve T cells; (2) in IPF, circulating neutrophils, eosinophils and naïve T cells were associated with lung function abnormalities; (3) patients whose disease progressed during the 12 months of follow-up showed evidence of cytotoxic dysregulation, with increased CD8+CD28- T cells, decreased naïve T cells and an inverted CD4/CD8 ratio at baseline; and (4) blood cell alterations were stable over time in survivors. (4) IPF is associated with abnormalities in circulating immune cells, particularly in the cytotoxic cell domain. Patients with progressive IPF, despite antifibrotic therapy, present an over-activated and exhausted immunophenotype at diagnosis, which is maintained over time.
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Antígenos CD28 , Fibrosis Pulmonar Idiopática , Humanos , Fibrosis Pulmonar Idiopática/diagnóstico , Linfocitos T , Citometría de Flujo , Gravedad del Paciente , Progresión de la EnfermedadRESUMEN
BACKGROUND: Human Gut Microbiota (HGM) is composed of more than one thousand species, playing an important role in the health status of individuals. Dysbiosis (an HGM imbalance) is augmented as chronic kidney disease (CKD) progresses, as loss of kidney function accelerates. Increased antibiotic use in CKD subjects and consumption of nephrotoxic heavy metals and metalloids such as lead, cadmium, arsenic, and mercury in tap water increases the dysbiosis state. Studies in people with stage 3 CKD are complex to carry out, mainly because patients are self-reliant who rarely consult a specialist. The current work focused on this type of patient. RESULTS: Lead and arsenic-resistant bacteria were obtained from self-reliant (that stands on its own) stage 3 CKD subjects. Pathogen-related Firmicutes and Proteobacteria genus bacteria were observed. Resistance and potentiation of antibiotic effects in the presence of metal(loid)s in vitro were found. Furthermore, the presence of the following genes markers for antibiotic and metal(loid) resistance were identified by qPCR: oxa10, qnrB1, mphB, ermB, mefE1, arr2, sulll, tetA, floR, strB, dhfr1, acrB, cadA2k, cadA3k, arsC, pbrA. We observed a decrease in the number of metal resistance markers. CONCLUSIONS: The presence of cadA and arsC genetic markers of antibiotics and metal(loid)s resistance were detected in samples from stage 3 CKD subjects. Lower gene amplification in advanced stages of CKD were also observed, possibly associated with a decrease in resident HGM during kidney disease progression.
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Arsénico , Microbioma Gastrointestinal , Metales Pesados , Insuficiencia Renal Crónica , Antibacterianos/farmacología , Bacterias/genética , Farmacorresistencia Microbiana , Disbiosis/microbiología , HumanosRESUMEN
BACKGROUND: Different clinical predictors of physical activity (PA) have been described in idiopathic pulmonary fibrosis (IPF), but studies are lacking evaluating the potential role of muscle strength and anxiety and depression symptoms in PA limitation. Moreover, little is known about the impact of changes in PA in the course of the disease. The aim of the present study was to investigate the relationship between baseline PA and a wide range of variables in IPF, to assess its longitudinal changes at 12 months and its impact on progression free-survival. METHODS: PA was assessed by accelerometer and physiological, clinical, psychological factors and health-related quality of life were evaluated in subjects with IPF at baseline and at 12 month follow-up. Predictors of PA were determined at baseline, evolution of PA parameters was described and the prognostic role of PA evolution was also established. RESULTS: Forty participants with IPF were included and 22 completed the follow-up. At baseline, subjects performed 5765 (3442) daily steps and spent 64 (44) minutes/day in moderate to vigorous PA. Multivariate regression models showed that at baseline, a lower six-minute walked distance, lower quadriceps strength (QMVC), and a higher depression score in the Hospital Anxiety and Depression scale were associated to lower daily step number. In addition, being in (Gender-Age-Physiology) GAP III stage, having a BMI ≥ 25 kg/m2 and lower QMVC or maximum inspiratory pressure were factors associated with sedentary behaviour. Adjusted for age, gender and forced vital capacity (FVC) (%pred.) a lower progression-free survival was evidenced in those subjects that decreased PA compared to those that maintained, or even increased it, at 12 months [HR 12.1 (95% CI, 1.9-78.8); p = 0.009]. CONCLUSION: Among a wide range of variables, muscle strength and depression symptoms have a predominant role in PA in IPF patients. Daily PA behaviour and its evolution should be considered in IPF clinical assessment and as a potential complementary indicator of disease prognosis.
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Fibrosis Pulmonar Idiopática , Ejercicio Físico , Humanos , Lactante , Fuerza Muscular , Calidad de Vida , Conducta SedentariaRESUMEN
BACKGROUND: In breeding programs, the selection of cultivars with the highest yield potential consisted in the selection of the yield per se, which resulted in cultivars with higher grains per spike (GN) and occasionally increased grain weight (GW) (main numerical components of the yield). In this study, quantitative trait loci (QTL) for GW, GN and spike fertility traits related to GN determination were mapped using two doubled haploid (DH) populations (Baguette Premium 11 × BioINTA 2002 and Baguette 19 × BioINTA 2002). RESULTS: In total 305 QTL were identified for 14 traits, out of which 12 QTL were identified in more than three environments and explained more than 10% of the phenotypic variation in at least one environment. Eight hotspot regions were detected on chromosomes 1A, 2B, 3A, 5A, 5B, 7A and 7B in which at least two major and stable QTL sheared confidence intervals. QTL on two of these regions (R5A.1 and R5A.2) have previously been described, but the other six regions are novel. CONCLUSIONS: Based on the pleiotropic analysis within a robust physiological model we conclude that two hotspot genomic regions (R5A.1 and R5A.2) together with the QGW.perg-6B are of high relevance to be used in marker assisted selection in order to improve the spike yield potential. All the QTL identified for the spike related traits are the first step to search for their candidate genes, which will allow their better manipulation in the future.
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Sitios de Carácter Cuantitativo/genética , Triticum/genética , Cromosomas de las Plantas/genética , Haploidia , Fenotipo , FitomejoramientoRESUMEN
Population growth has been closely associated with agricultural production, since the first famine predicted by Malthus (1798) up to the Green Revolution of the past century. Today, we continue to face increasing demand for food and crop production (Tilman et al., 2011). Considering the combined caloric or protein content of the 275 major crops used directly as human foods or as livestock and fish feeds, Tilman et al. (2011) forecast a 100% increase in global demand for crops from 2005 to 2050. Meeting this demand with the lowest impact on the environment could be achieved by sustainable intensification of existing cropland with reduced land clearing (Tilman et al., 2011; Fischer and Connor, 2018).
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Agricultura , Productos Agrícolas , Animales , Producción de Cultivos , PredicciónRESUMEN
Fruiting efficiency (FE, grains per g of spike dry weight at anthesis) was proposed as a promising spike trait to improve wheat yield potential, based on its functional relationship with grain number determination and the evidence of trait variability in elite germplasm. During the last few years, we have witnessed great advances in the understanding of the physiological and genetic basis of this trait. The present review summarizes the recent heritability estimations and the genetic gains obtained when fruiting efficiency was measured at maturity (FEm, grains per g of chaff) and used as selection criterion. In addition, we propose spike ideotypes for contrasting fruiting efficiencies based on the fertile floret efficiency (FFE, fertile florets per g of spike dry weight at anthesis) and grain set (grains per fertile floret), together with other spike fertility-related traits. We also review novel genes and quantitative trait loci available for using marker-assisted selection for fruiting efficiency and other spike fertility traits. The possible trade-off between FE and grain weight and the genes reported to alter this relation are also considered. Finally, we discuss the benefits and future steps towards the use of fruiting efficiency as a selection criterion in breeding programs.
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Fitomejoramiento , Triticum , Grano Comestible , Fenotipo , Sitios de Carácter Cuantitativo/genética , Triticum/genéticaRESUMEN
In May 2020, Uruguay was one of the few Latin American countries that had managed to control the outbreak of COVID-19 without mandatory curfews or quarantines. However, several social distancing measures created a major disruption in different aspects of the daily life of Uruguayan citizens. In this context, the objectives of the present work were i) to identify changes in eating habits perceived by Uruguayan citizens as a consequence of the COVID-19 pandemic, and ii) to explore factors associated with different perceived changes on eating habits. A cross-sectional online study was conducted with 891 participants, recruited using an advertisement on Facebook and Instagram. Fifty-one percent of the participants indicated that their eating habits had changed since the detection of the first cases of COVID-19 in Uruguay. Large heterogeneity in the categorization of the changes existed: 45% of the participants regarded the changes as positive, 32% as negative and 23% as neither positive nor negative. A multinomial logistic regression analysis was used to study the influence of explanatory variables in the likelihood of belonging to groups who reported different changes in eating habits (no changes, positive, negative, or neither positive nor negative changes). Household income and reliance on instrumental and emotional support increased the likelihood of reporting positive changes in eating habits, whereas negative changes were associated with a reduction in household income due to COVID-19 and the coping strategies self-distraction and self-blaming. Insights for policy making to reinforce positive effects and minimize threats to healthy eating are discussed.
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COVID-19 , Pandemias , Estudios Transversales , Dieta Saludable , Conducta Alimentaria , Humanos , SARS-CoV-2 , Encuestas y Cuestionarios , Uruguay/epidemiologíaRESUMEN
Fibrosing interstitial lung diseases (ILDs) are chronic and ultimately fatal age-related lung diseases characterized by the progressive and irreversible accumulation of scar tissue in the lung parenchyma. Over the past years, significant progress has been made in our incomplete understanding of the pathobiology underlying fibrosing ILDs, in particular in relation to diverse age-related processes and cell perturbations that seem to lead to maladaptation to stress and susceptibility to lung fibrosis. Growing evidence suggests that a specific biological phenomenon known as cellular senescence plays an important role in the initiation and progression of pulmonary fibrosis. Cellular senescence is defined as a cell fate decision caused by the accumulation of unrepairable cellular damage and is characterized by an abundant pro-inflammatory and pro-fibrotic secretome. The senescence response has been widely recognized as a beneficial physiological mechanism during development and in tumour suppression. However, recent evidence strengthens the idea that it also drives degenerative processes such as lung fibrosis, most likely by promoting molecular and cellular changes in chronic fibrosing processes. Here, we review how cellular senescence may contribute to lung fibrosis pathobiology, and we highlight current and emerging therapeutic approaches to treat fibrosing ILDs by targeting cellular senescence.
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Senescencia Celular/fisiología , Fibrosis Pulmonar Idiopática/etiología , Pulmón/patología , Progresión de la Enfermedad , Fibrosis , Humanos , Fibrosis Pulmonar Idiopática/patología , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/patologíaRESUMEN
Coupling anthesis date to the most suitable environmental conditions is critical for wheat (Triticum aestivum L.) adaptation and yield potential. Development to anthesis is controlled by temperature and photoperiod. Response to photoperiod is chiefly modulated by Ppd-1 genes, but their effect on the quantitative response to photoperiod of (i) time to anthesis and (ii) pre-anthesis phases remains largely unknown. A photoperiod-sensitive spring cultivar, Paragon, and near-isogenic lines of it carrying different combinations of Ppd-1a insensitivity alleles were tested under a wide range of photoperiods, including switches in photoperiod at the onset of stem elongation. Using multimodel inference we found that Ppd-1a alleles reduced photoperiod sensitivity of (i) emergence to anthesis and (ii) emergence to onset of stem elongation, both in a less than additive manner, while threshold photoperiod and intrinsic earliness were unaffected. Sensitivity to current photoperiod from onset of stem elongation to flag leaf and from then to anthesis was milder than for previous phases and was not related to variability in Ppd-1. However, 'memory' effects of previously experienced photoperiod on the duration from onset of stem elongation to flag leaf were related to variability in Ppd-1. The characterization and quantification provided here of the effects on development of Ppd-1 allelic combinations should help increase accuracy of genotype-to-phenotype models in predicting wheat phenology.
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Flores/crecimiento & desarrollo , Modelos Biológicos , Fotoperiodo , Triticum/genética , Triticum/crecimiento & desarrolloRESUMEN
KEY MESSAGE: This study identified and validated two QTL associated with spike fertile floret and fruiting efficiencies. They represent two new loci to use in MAS to improve wheat yield potential. The spike fruiting efficiency (FE-grains per unit spike dry weight at anthesis, GN/SDW) is a promising trait to improve wheat yield potential. It depends on fertile floret efficiency (fertile florets per unit SDW-FFE, FF/SDW) and grain set (grains per fertile floret-GST). Given its difficult measurement, it is often estimated as the grains per unit of nongrain spike dry weight at maturity (FEm). In this study, quantitative trait loci (QTL) were mapped using a double haploid population (Baguette 19/BIOINTA 2002, with high and low FE, respectively) genotyped with the iSelect 90 K SNP array and evaluated in five environments. We identified 37 QTL, but two were major with an R2 > 10% and stable for being at least present in three environments: the QFEm.perg-3A (on Chr. 3A, 51.6 cM, 685.12 Mb) for FEm and the QFFE.perg-5A (on Chr. 5A, 42.1 cM, 461.49 Mb) for FFE, FE and FEm. Both QTL were validated using two independent F2 populations and KASP markers. For the most promising QTL, QFFE.perg-5A, the presence of the allele for high FFE resulted in + 4% FF, + 9% GN, + 13% GST, + 16% yield gSDW-1 and + 5% yield spike-1. QFEm.perg-3A and QFFE.perg-5A represent two new loci to use in MAS to improve wheat yield potential.
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Flores/crecimiento & desarrollo , Sitios de Carácter Cuantitativo , Semillas/crecimiento & desarrollo , Triticum/genética , Alelos , Mapeo Cromosómico , Genotipo , Haploidia , Fenotipo , PoliploidíaRESUMEN
PURPOSE OF REVIEW: Sarcoidosis is a granulomatous systemic disease of unknown cause where the lung is the most frequently affected organ. Therapeutic management of the disease is challenging as clinical presentation and prognosis are very heterogeneous. In the present review, we will summarize the main advances in sarcoidosis therapy. RECENT FINDINGS: Current sarcoidosis therapies are categorized in three lines: glucocorticoids (first line), immunosuppressants (second line), and biologics (third line). Recent glucocorticoid studies have reported that efficacy could be similar with high and low doses, but with an increase in side effects with higher doses. In immunosuppressants, recent publications in mycophenolate and repository corticotropin injection (RCI) have added more information in their use and efficacy. Finally, new evidence has been published in the use of antitumor necrosis factor (anti-TNFα) agents in refractory cardiac sarcoidosis and neurosarcoidosis. SUMMARY: Sarcoidosis therapy is constantly evolving, and new drugs have been added to the recommended treatments. However, extensive clinical trials are still necessary to optimize the current recommendations.
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Productos Biológicos/uso terapéutico , Glucocorticoides/uso terapéutico , Inmunosupresores/uso terapéutico , Sarcoidosis/tratamiento farmacológico , Cardiomiopatías/tratamiento farmacológico , Enfermedades del Sistema Nervioso Central/tratamiento farmacológico , Humanos , Pulmón , Pronóstico , Sarcoidosis Pulmonar/tratamiento farmacológico , Inhibidores del Factor de Necrosis Tumoral/uso terapéuticoRESUMEN
Small molecule libraries for virtual screening are becoming a well-established tool for the identification of new hit compounds. As for experimental assays, the library quality, defined in terms of structural complexity and diversity, is crucial to increase the chance of a successful outcome in the screening campaign. In this context, Diversity-Oriented Synthesis has proven to be very effective, as the compounds generated are structurally complex and differ not only for the appendages, but also for the molecular scaffold. In this work, we automated the design of a library of lactams by applying a Diversity-Oriented Synthesis strategy called Build/Couple/Pair. We evaluated the novelty and diversity of these compounds by comparing them with lactam moieties contained in approved drugs, natural products, and bioactive compounds from ChEMBL. Finally, depending on their scaffold we classified them into ß-, γ-, δ-, ε-, and isolated, fused, bridged and spirolactam groups and we assessed their drug-like and lead-like properties, thus providing the value of this novel in silico designed library for medicinal chemistry applications.
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Diseño de Fármacos , Lactamas/química , Bibliotecas de Moléculas Pequeñas/química , Productos Biológicos/química , Técnicas Químicas Combinatorias , Lactamas/metabolismo , Bibliotecas de Moléculas Pequeñas/metabolismoRESUMEN
Lengthening the pre-anthesis period of stem elongation (or late-reproductive phase, LRP) through altering photoperiod sensitivity has been suggested as a potential means to increase the number of fertile florets at anthesis (NFF) in wheat. However, little is known about the effects that the Ppd-1 genes modulating plant response to photoperiod may have on reproductive development. Here, five genotypes with either sensitive (b) or insensitive (a) alleles were grown in chambers under contrasting photoperiods (12 h or 16 h) to assess their effects. The genotypes consisted of the control cultivar Paragon (three Ppd-1b) and four near-isogenic lines of Paragon with Ppd-1a alleles introgressed from: Chinese Spring (Ppd-B1a), GS-100 (Ppd-A1a), Sonora 64 (Ppd-D1a), and Triple Insensitive (three Ppd-1a). Under a 12-h photoperiod, NFF in the genotypes followed the order three Ppd-1b > Ppd-B1a > Ppd-A1a > Ppd-D1a > three Ppd-1a. Under a 16-h photoperiod the differences were milder, but three Ppd-1b still had a greater NFF than the rest. As Ppd-1a alleles shortened the LRP, spikes were lighter and the NFF decreased. The results demonstrated for the first time that Ppd-1a decreases the maximum number of florets initiated through shortening the floret initiation phase, and this partially explained the variations in NFF. The most important impact of Ppd-1a alleles, however, was related to a reduction in survival of floret primordia, which resulted in the lower NFF. These findings reinforce the idea that an increased duration of the LRP, achieved through photoperiod sensitivity, would be useful for increasing wheat yield potential.
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Flores/genética , Genes de Plantas , Fotoperiodo , Triticum/genética , Alelos , Flores/crecimiento & desarrollo , Genotipo , Triticum/crecimiento & desarrolloRESUMEN
HaHB4 is a sunflower transcription factor belonging to the homeodomain-leucine zipper I family whose ectopic expression in Arabidopsis triggers drought tolerance. The use of PCR to clone the HaHB4 coding sequence for wheat transformation caused unprogrammed mutations producing subtle differences in its activation ability in yeast. Transgenic wheat plants carrying a mutated version of HaHB4 were tested in 37 field experiments. A selected transgenic line yielded 6% more (P<0.001) and had 9.4% larger water use efficiency (P<0.02) than its control across the evaluated environments. Differences in grain yield between cultivars were explained by the 8% improvement in grain number per square meter (P<0.0001), and were more pronounced in stress (16% benefit) than in non-stress conditions (3% benefit), reaching a maximum of 97% in one of the driest environments. Increased grain number per square meter of transgenic plants was accompanied by positive trends in spikelet numbers per spike, tillers per plant, and fertile florets per plant. The gene transcripts associated with abiotic stress showed that HaHB4's action was not dependent on the response triggered either by RD19 or by DREB1a, traditional candidates related to water deficit responses. HaHB4 enabled wheat to show some of the benefits of a species highly adapted to water scarcity, especially in marginal regions characterized by frequent droughts.