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Inflammation is a central pathogenic feature of the acute respiratory distress syndrome (ARDS) in COVID-19. Previous pathologies such as diabetes, autoimmune or cardiovascular diseases become risk factors for the severe hyperinflammatory syndrome. A common feature among these risk factors is the subclinical presence of cellular stress, a finding that has gained attention after the discovery that BiP (GRP78), a master regulator of stress, participates in the SARS-CoV-2 recognition. Here, we show that BiP serum levels are higher in COVID-19 patients who present certain risk factors. Moreover, early during the infection, BiP levels predict severe pneumonia, supporting the use of BiP as a prognosis biomarker. Using a mouse model of pulmonary inflammation, we observed increased levels of cell surface BiP (cs-BiP) in leukocytes during inflammation. This corresponds with a higher number of neutrophiles, which show naturally high levels of cs-BiP, whereas alveolar macrophages show a higher than usual exposure of BiP in their cell surface. The modulation of cellular stress with the use of a clinically approved drug, 4-PBA, resulted in the amelioration of the lung hyperinflammatory response, supporting the anti-stress therapy as a valid therapeutic strategy for patients developing ARDS. Finally, we identified stress-modulated proteins that shed light into the mechanism underlying the cellular stress-inflammation network in lungs.

Inflammation is a central pathogenic feature of the acute respiratory distress syndrome (ARDS) in COVID-19. Previous pathologies such as diabetes, autoimmune or cardiovascular diseases become risk factors for the severe hyperinflammatory syndrome. A common feature among these risk factors is the subclinical presence of cellular stress, a finding that has gained attention after the discovery that BiP (GRP78), a master regulator of stress, participates in the SARS-CoV-2 recognition. Here, we show that BiP serum levels are higher in COVID-19 patients who present certain risk factors. Moreover, early during the infection, BiP levels predict severe pneumonia, supporting the use of BiP as a prognosis biomarker. Using a mouse model of pulmonary inflammation, we demonstrate that cell surface BiP (cs-BiP) responds by increasing its levels in leukocytes. Neutrophiles show the highest levels of cs-BiP and respond by increasing their population, whereas alveolar macrophages increase their levels of cs-BiP. The modulation of cellular stress with the use of a clinically approved drug, 4-PBA, resulted in the amelioration of the lung hyperinflammatory response, supporting the anti-stress therapy as a valid therapeutic strategy for patients developing ARDS. Finally, we identified stress-modulated proteins that shed light into the mechanism underlying the cellular stress-inflammation network in lungs.

A high risk of thrombotic complications has been observed among severely ill COVID-19 patients. Viscoelastic tests (VET) have shown a hypercoagulable profile in these patients, although so far there is no clear evidence on the use of these tools as predictors of risk in the clinical course of patients. In this study we aimed to evaluate the association between Quantra® sonorheometry VET parameters, standard coagulation tests and inflammatory markers in 69 patients with COVID-19 on hospital admission with disease severity and outcome. Inflammatory markers were elevated in a high percentage of patients, as were coagulation-related parameters such as fibrinogen and D-dimer levels. Quantra® sonorheometry analysis revealed increased clot stiffness (CS), especially due to increased fibrinogen contribution (FCS) in 63.7%. Analysis of clot stability to lysis (CSL) on the Quantra showed a value of 100%, suggesting hypofibrinolysis, in 32.4%. Age > 65 years, elevated values of fibrinogen, D-dimer, LDH, increased CS and CSL were significantly associated with worsening disease. The combination of elevated FCS and D-dimer values showed a particularly high prognostic value in distinguishing patients with severe symptomatology. In conclusion, FCS measured by Quantra® system and its combination with D-dimer could be established as a powerful tool to identify poor prognosis in COVID-19 patients on hospital admission.

Yellow Stripe-Like (YSL) proteins are a family of plant transporters that are typically involved in transition metal homeostasis. Three of the four YSL clades (I, II and IV) transport metals complexed with the non-proteinogenic amino acid nicotianamine or its derivatives. No such capability has been shown for any member of clade III, but the link between these YSLs and metal homeostasis could be masked by functional redundancy. We studied the role of the clade III YSL protein MtSYL7 in Medicago truncatula nodules. MtYSL7, which encodes a plasma membrane-bound protein, is mainly expressed in the pericycle and cortex cells of the root nodules. Yeast complementation assays revealed that MtSYL7 can transport short peptides. M. truncatula transposon insertion mutants with decreased expression of MtYSL7 had lower nitrogen fixation rates and showed reduced plant growth whether grown in symbiosis with rhizobia or not. YSL7 mutants accumulated more copper and iron in the nodules, which is likely to result from the increased expression of iron uptake and delivery genes in roots. Taken together, these data suggest that MtYSL7 plays an important role in the transition metal homeostasis of nodules and symbiotic nitrogen fixation.

Legumes form a symbiosis with rhizobia that convert atmospheric nitrogen (N2) to ammonia and provide it to the plant in return for a carbon and nutrient supply. Nodules, developed as part of the symbiosis, harbor rhizobia that are enclosed in a plant-derived symbiosome membrane (SM) to form an organelle-like structure called the symbiosome. In mature nodules exchanges between the symbionts occur across the SM. Here we characterize Yellow Stripe-like 7 (GmYSL7), a Yellow stripe-like family member localized on the SM in soybean (Glycine max) nodules. It is expressed specifically in infected cells with expression peaking soon after nitrogenase becomes active. Unlike most YSL family members, GmYSL7 does not transport metals complexed with phytosiderophores. Rather, it transports oligopeptides of between four and 12 amino acids. Silencing GmYSL7 reduces nitrogenase activity and blocks infected cell development so that symbiosomes contain only a single bacteroid. This indicates the substrate of YSL7 is required for proper nodule development, either by promoting symbiosome development directly or by preventing inhibition of development by the plant. RNAseq of nodules where GmYSL7 was silenced suggests that the plant initiates a defense response against rhizobia with genes encoding proteins involved in amino acid export downregulated and some transcripts associated with metal homeostasis altered. These changes may result from the decrease in nitrogen fixation upon GmYSL7 silencing and suggest that the peptide(s) transported by GmYSL7 monitor the functional state of the bacteroids and regulate nodule metabolism and transport processes accordingly. Further work to identify the physiological substrate for GmYSL7 will allow clarification of this role.

It is not known whether sequential outpatient parenteral antimicrobial (OPAT) is as safe and effective as conventional hospitalization in patients with S. aureus bacteremia (SAB). A post-hoc analysis of the comparative effectiveness of conventional hospitalization versus sequential OPAT was performed in two prospective Spanish cohorts of patients with S. aureus bacteremia. The PROBAC cohort is a national, multicenter, prospective observational cohort of patients diagnosed in 22 Spanish hospitals between October 2016 and March 2017. The DOMUS OPAT cohort is a prospective observational cohort including patients from two university hospitals in Seville, Spain from 2012 to 2021. Multivariate regression was performed, including a propensity score (PS) for receiving OPAT, stratified analysis according to PS quartiles, and matched pair analyses based on PS. Four hundred and thirteen patients were included in the analysis: 150 in sequential OPAT and 263 in the full hospitalization therapy group. In multivariate analysis, including PS and center effect as covariates, 60-day treatment failure was lower in the OPAT group than in the full hospitalization group (p < 0.001; OR 0.275, 95%CI 0.129−0.584). In the PS-based matched analyses, sequential treatment under OPAT was not associated with higher 60-day treatment failure (p = 0.253; adjusted OR 0.660; % CI 0.324−1.345). OPAT is a safe and effective alternative to conventional in-patient therapy for completion of treatment in well-selected patients with SAB, mainly those associated with a low-risk source and without end-stage kidney disease., Supported by Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, CIBERINFEC (CB21/13/00006; CB21/13/00012; CB21/13/00068; CB21/13/00083), co-financed by European Development Regional Fund “A way to achieve Europe”, Operative Program Intelligence Growth 2014-2020.

Exploiting the relationship between the nutritional properties of seeds and the genetic background, constitutes an essential analysis which contributes to broadening our knowledge regarding the control of the nutritional quality of seeds or any other edible plant structure. This constitutes an important aspect when aiming at improving the nutritional characteristics properties of crops, including those of Chenopodium quinoa Willd (quinoa) which is intended to be one of the main nutrient sources ensuring food security worldwide. Changes in the nutritional properties of quinoa seeds due to the influence exerted by the environment, the genotype, or their interaction, have been already described in previous works, but there is an important limitation in the analyses carried out, including the outcomes that can be translated into agronomical practices by which quality can be improved selecting the most adequate genotype. In the present study, several seed nutritional-related parameters from fifteen quinoa cultivars grown in a particular environmental context were analyzed aiming at targeting compounds that can be determinants of seed quality. Important agronomical and nutritional differences were found among cultivars such as distinct mineral or protein contents and seed viability. More importantly, our analyses revealed key correlations between seed quality-related traits in some cultivars, including those that relate yield and antioxidants or the germination rate. These results highlight the importance of considering the genotypic variation in quinoa when selecting improved quinoa varieties with the best nutritional characteristics for new cultivation environments.

Chenopodium quinoa Willd (quinoa) has acquired an increased agronomical and nutritional relevance due to the capacity of adaptation to different environments and the exceptional nutritional properties of their seeds. These include high mineral and protein contents, a balanced amino acid composition, an elevated antioxidant capacity related to the high phenol content, and the absence of gluten. Although it is known that these properties can be determined by the environment, limited efforts have been made to determine the exact changes occurring at a nutritional level under changing environmental conditions in this crop. To shed light on this, this study aimed at characterizing variations in nutritional-related parameters associated with the year of cultivation and different genotypes. Various nutritional and physiological traits were analyzed in seeds of different quinoa cultivars grown in the field during three consecutive years. We found differences among cultivars for most of the nutritional parameters analyzed. It was observed that the year of cultivation was a determinant factor in every parameter studied, being 2018 the year with lower yields, germination rates, and antioxidant capacity, but higher seed weights and seed protein contents. Overall, this work will greatly contribute to increase our knowledge of the impact of the environment and genotype on the nutritional properties of quinoa seeds, especially in areas that share climatic conditions to Southern Europe., This work was supported by the Ministerio de Ciencia e Innovación (MICINN, Spain) (PID2019-105748RA-I00), the Madrid Government (Comunidad de Madrid-Spain) under the Multiannual Agreement with Universidad Autónoma de Madrid in the line of action encouraging youth research doctors, in the context of the V PRICIT (Regional Programme of Research and Technological Innovation) (SI1/PJI/2019-00124), the CYTED (ValSe-Food 119RT0567), the FPI UAM Fellowship Programme 2019 (to SG-R), and the Ramón y Cajal Programme 2019 (to MR).

Quinoa (Chenopodium quinoa Willd.) is receiving increasing attention globally due to the high nutritional value of its seeds, and the ability of this crop to cope with stress. In the current climate change scenario, valorization of crop byproducts is required to support a climate-smart agriculture. Furthermore, research works characterizing and evaluating quinoa stems and their putative uses are scarce. In this work, straw yield and composition, and the relative feed value of five quinoa varieties, were analyzed in two consecutive years (2017–2018) under field conditions in Southwestern Europe. High temperatures were recorded during the 2017 growing season resulting in significantly decreased straw yield and improved feed value, associated with compositional changes under elevated temperatures. Crude protein, ash, phosphorus, and calcium contents were higher under high temperatures, whereas fiber contents decreased. The relative feed value was also higher in 2017 and differed among varieties. Differences among varieties were also found in straw yield, and contents of phosphorus, potassium, and calcium. Overall, the results presented here support a sustainable quinoa productive system by encouraging straw valorization and shedding light on the mechanisms underlying heat-stress responses in this crop.

© 2020 The Author(s)., [Objectives]: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters., [Methods]: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs)., [Results]: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22–0.47; p < 0.001) for tocilizumab, 0.82 (0.71–1.30; p 0.82) for IHDC, 0.61 (0.43–0.86; p 0.006) for PDC, and 1.17 (0.86–1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02–0.17; p < 0.001)., [Conclusions]: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situation., IJ has received honoraria for participating in an advisory board from Gilead Sciences, and for educational activities from ViiV. JB has received research grants from AbbVie, Gilead Sciences, Merck, and ViiV, and honoraria for being a speaker or advisory board participation from AbbVie, Gilead Sciences, Janssen, Merck, and ViiV. JRA received fees for participating in an advisory board, being a speaker, and research grant support from Viiv, Janssen, Gilead, MSD, Teva, Alexa and Serono. PR is involved as speaker or advisory board participant for Gilead Sciences, AbbVie and ViiV. JR-B, JP, JC and MY have no conflicts of interest to declare. SAM-COVID was funded by Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (COV20/01031) co-funded by European Union (ERDF/ESF, “Investing in your future”) and Fundación SEIMC/GeSIDA. In addition, Juan Berenguer, Jesús Rodríguez-Baño, Inmaculada Jarrín, Jordi Carratalá, Jerónimo Pachón, and José R Arribas received funding for research from Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades – co- financed by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014–2020 through the networks: Spanish AIDS Research Network (RIS) [RD16/0025/0017 (JB), RD16/0025/0018 (JRA), RD16/0025/00XX (IJ)] and Spanish Network for Research in Infectious Diseases (REIPI)[RD16/0016/0001 (JRB), RD16/0016/0005 (JC), and RD16/0016/0009 (JP).

CarbaPIRASOA team., [Background] Carbapenem-resistant Gram-negative bacilli (CR-GNB) are among the most threatening microorganisms worldwide and carbapenem use facilitates their spread. Antimicrobial stewardship programmes (ASPs) can help to optimize the use of antibiotics. This study evaluates the impact of a multifaceted educational ASP on carbapenem use and on the epidemiology of CR-GNB., [Methods] We conducted a quasi-experimental, time-series study in seven hospitals, from January 2014 to September 2018. The key intervention was composed of educational interviews promoting the appropriate use of carbapenems. The primary endpoints were carbapenem consumption and incidence density (ID) of CR-GNB. All non-duplicated CR-GNB clinical isolates were tested using phenotypic assays and PCR for the presence of carbapenemases. Joinpoint regression and interrupted time-series analyses were used to determine trends., [Results] A decrease in carbapenem consumption throughout the study period [average quarterly percentage change (AQPC) −1.5%, P, [Conclusions] In conclusion, a multifaceted, educational interview-based ASP targeting carbapenem prescribing reduced carbapenem use and the ID of CR-A. baumannii., This work was funded by the Spanish Infectious Diseases and Clinical Microbiology Society (SEIMC).

PROBAC REIPI/GEIH-SEIMC/SAEI., [Background] Catheter-related bloodstream infections (CRBSIs) increase morbidity and mortality, prolong hospitalization and generate considerable medical costs. Recent guidelines for CRBSI recommend empirical therapy against Gram-positive bacteria (GPB) and restrict coverage for Gram-negative bacteria (GNB) only to specific circumstances., [Objectives]To investigate predictors of GNB aetiology in CRBSI and to assess the predictors of outcome in patients with CRBSI., [Methods] Patients with CRBSI were selected from the PROBAC cohort, a prospective, observational, multicentre national cohort study including patients with bloodstream infections consecutively admitted to 26 Spanish hospitals in a 6 month period (October 2016–March 2017). Outcome variables were GNB aetiology and 30 day mortality. Adjusted analyses were performed by logistic regression., [Results] Six hundred and thirty-one episodes of CRBSI were included in the study. Risk factors independently related to GNB aetiology were central venous catheter (CVC) [OR 1.60 (95% CI: 1.05–2.44), P = 0.028], sepsis/septic shock [OR: 1.76 (95% CI: 1.11–2.80), P = 0.016], antibiotic therapy in the previous 30 days [OR: 1.56 (95% CI: 1.02–2.36), P = 0.037], neutropenia, [Conclusions] Our study reinforces the recommendation that empirical coverage should cover GNB in patients presenting with sepsis/septic shock and in neutropenic patients. Catheter removal and adequate empirical treatment were both protective factors against mortality in patients with CRBSI., This study was funded by Plan Nacional de I+D+i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, through the following grants: Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001; RD16/0016/0007; RD16/0016/0008; RD16/0016/0012), co-financed by European Development Regional Fund ‘A way to achieve Europe’, Operative Program Intelligent Growth 2014–2020, and PI16/01432. F. Caló enjoyed an ESCMID Observership grant at Hospital Universitario Virgen Macarena to develop this research.

13 Pags.- 5 Figs. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Experimental Biology., Symbiotic nitrogen fixation carried out in legume root nodules requires transition metals. These nutrients are delivered by the host plant to the endosymbiotic nitrogen-fixing bacteria living within the nodule cells, a process in which vascular transport is essential. As members of the Yellow Stripe-Like (YSL) family of metal transporters are involved in root to shoot transport, they should also be required for root to nodule metal delivery. The genome of the model legume Medicago truncatula encodes eight YSL proteins, four of them with a high degree of similarity to Arabidopsis thaliana YSLs involved in long-distance metal trafficking. Among them, MtYSL3 is a plasma membrane protein expressed by vascular cells in roots and nodules and by cortical nodule cells. Reducing the expression level of this gene had no major effect on plant physiology when assimilable nitrogen was provided in the nutrient solution. However, nodule functioning was severely impaired, with a significant reduction of nitrogen fixation capabilities. Further, iron and zinc accumulation and distribution changed. Iron was retained in the apical region of the nodule, while zinc became strongly accumulated in the nodule veins in the ysl3 mutant. These data suggest a role for MtYSL3 in vascular delivery of iron and zinc to symbiotic nitrogen fixation., This research was funded by a European Research Council Starting Grant (ERC-2013-StG-335284) and the Spanish State Research Agency (AEI) grant (AGL2015-65866-P) to MGG, and a AEI grant (AGL2016-75226-R) to JA and AA-F co-financed by the European Regional Development Fund (FEDER). RC-R and FJJ-P were supported by a Formación del Personal Investigador fellowship (BES2013-062674 and BES-2017-082913, respectively). IA was the recipient of a Juan de la Cierva- Formación postdoctoral fellowship from Ministerio de Ciencia, Innovación y Universidades (FJCI-2017- 33222). VE was partially funded by the Severo Ochoa Programme for Centres of Excellence in R&D from the AEI (grant SEV-2016- 0672) received by the Centro de Biotecnología y Genómica de Plantas (UPM-INIA). Development of the M. truncatula Tnt1 mutant population was, in part, funded by the National Science Foundation, USA (DBI-0703285) to KSM. AM and HK and the µXRF measurements were supported by the Ministry of Education, Youth and Sports of the Czech Republic with co-financing from the European Union (grant ‘KOROLID’, CZ.02.1.01/0.0/0.0/15_003/0000336) and the Czech Academy of Sciences (RVO: 60077344).

Background Legumes comprise important crops that offer major agronomic benefits, including the capacity of establishing symbiosis with rhizobia, fixing atmospheric N2. It has been proven that legumes are particularly susceptible to boron (B) stress, which leads to important yield penalties. Boron (B) deficiency or toxicity in plants causes the inhibition of growth and an altered development. Under such conditions, the participation of two distinct protein families (the major intrinsic protein family MIP and the Boron transporter family BOR) is required to minimize detrimental effects caused by B stress. However, in legumes, little is known about the transport mechanisms responsible for B uptake and distribution, especially under deficiency. Results A Medicago truncatula protein, MtNIP5;1 (Medtr1g097840) (homologous to the Arabidopsis thaliana AtNIP5;1) was identified as a novel legume B transporter involved in B uptake under deficiency. Further analyses revealed that this M. truncatula aquaporin expression was boron-regulated in roots, being induced under deficiency and repressed under toxicity. It localizes at the plasma membrane of root epidermal cells and in nodules, where B plays pivotal roles in symbiosis. Furthermore, the partial complementation of the nip5;1–1 A. thaliana mutant phenotype under B deficiency supports a functional role of MtNIP5;1 as a B transporter in this legume model plant. Conclusions The results here presented support a functional role of MtNIP5;1 in B uptake under deficiency and provides new insights into B transport mechanisms in legume species.

Legumes form a symbiosis with rhizobia that convert atmospheric nitrogen (N2) to ammonia which they provide to the plant in return for a carbon and nutrient supply. Nodules, developed as part of the symbiosis, harbor rhizobia which are enclosed in the plant-derived symbiosome membrane (SM), to form a symbiosome. In the mature nodule all exchanges between the symbionts occur across the SM. Here we characterize GmYSL7, a member of Yellow stripe-like family which is localized to the SM in soybean nodules. It is expressed specifically in nodule infected cells with expression peaking soon after nitrogenase becomes active. Although most members of the family transport metal complexed with phytosiderophores, GmYSL7 does not. It transports oligopeptides of between four and 12 amino acids. Silencing of GmYSL7 reduces nitrogenase activity and blocks development when symbiosomes contain a single bacteroid. RNAseq of nodules in which GmYSL7 is silenced suggests that the plant initiates a defense response against the rhizobia. There is some evidence that metal transport in the nodules is dysregulated, with upregulation of genes encoding ferritin and vacuolar iron transporter family and downregulation of a gene encoding nicotianamine synthase. However, it is not clear whether the changes are a result of the reduction of nitrogen fixation and the requirement to store excess iron or an indication of a role of GmYSL7 in regulation of metal transport in the nodules. Further work to identify the physiological substrate for GmYSL7 will allow clarification of this role.One sentence summaryGmYSL7 is a symbiosome membrane peptide transporter that is essential for symbiotic nitrogen fixation that when silenced blocks symbiosome development.

Yellow Stripe-Like (YSL) proteins are a family of plant transporters typically involved in transition metal homeostasis. The substrate of three of the four YSL clades (clades I, II, and IV) are metal complexes with non-proteinogenic amino acid nicotianamine or its derivatives. No such transport capabilities have been shown for any member of the remaining clade (clade III), which is able to translocate short peptides across the membranes instead. The connection between clade III YSL members and metal homeostasis might have been masked by the functional redundancy characteristic of this family. This might have been circumvented in legumes through neofunctionalization of YSLs to ensure a steady supply of transition metals for symbiotic nitrogen fixation in root nodules. To test this possibility,Medicago truncatulaclade III transporter MtYSL7 has been studied both when the plant was fertilized with ammonium nitrate or when nitrogen had to be provided by endosymbiotic rhizobia within the root nodules. MtYSL7 is a plasma membrane protein expressed in the vasculature and in the nodule cortex. This protein is able to transport short peptides into the cytosol, although none with known metal homeostasis roles. ReducingMtYSL7expression levels resulted in diminished nitrogen fixation rates. In addition, nodules of mutant lines lackingYSL7accumulated more copper and iron, the later the likely result of increased expression in roots of iron uptake and delivery genes. The available data is indicative of a role of MtYSL7, and likely other clade III YSLs, in transition metal homeostasis.ONE SENTENCE SUMMARYMedicago truncatulaYSL7 is a peptide transporter required for symbiotic nitrogen fixation in legume nodules, likely controlling transition metal allocation to these organs.

Symbiotic nitrogen fixation carried out in legume root nodules requires transition metals. These nutrients are delivered by the host plant to the endosymbiotic nitrogen-fixing bacteria living with the nodule cells, a process in which vascular transport is essential. As occurs in root-to-shoot transport, members of the Yellow Stripe-Like (YSL) family of metal transporters should also be required for root-to-nodule metal delivery. The genome of the model legumeMedicago truncatulaencodes for eight YSL proteins, four of them with a high degree of similarity toArabidopsis thalianaYSLs involved in long-distance metal trafficking. Among them, MtYSL3 is a plasma membrane protein expressed by vascular cells in roots and nodules, and by cortical nodule cells. Reducing expression levels of this gene had no major effect on plant physiology when assimilable nitrogen was provided in the nutrient solution. However, nodule functioning was severely impaired, with a significant reduction of nitrogen fixation capabilities. Further, iron and zinc accumulation and distribution changed. Iron was retained in the apical region of the nodule, while zinc became strongly accumulated in the nodule veins in theysl3mutant. These data suggest a role of MtYSL3 in vascular delivery of iron and zinc to symbiotic nitrogen fixation.HighlightMedicago truncatulaYSL3 transporter is required for optimal nitrogen fixation in root nodules, mediating iron and zinc distribution in these organs.

Significant advances have been made in the last years trying to identify regulatory pathways that control plant responses to boron (B) deficiency. Still, there is a lack of a deep understanding of how they act regulating growth and development under B limiting conditions. Here, we analyzed the impact of B deficit on cell division leading to root apical meristem (RAM) disorganization. Our results reveal that inhibition of cell proliferation under the regulatory control of cytokinins (CKs) is an early event contributing to root growth arrest under B deficiency. An early recovery of QC46:GUS expression after transferring B-deficient seedlings to control conditions revealed a role of B in the maintenance of QC identity whose loss under deficiency occurred at later stages of the stress. Additionally, the D-type cyclin CYCD3 overexpressor and triple mutant cycd3;1-3 were used to evaluate the effect on mitosis inhibition at the G1-S boundary. Overall, this study supports the hypothesis that meristem activity is inhibited by B deficiency at early stages of the stress as it does cell elongation. Likewise, distinct regulatory mechanisms seem to take place depending on the severity of the stress. The results presented here are key to better understand early signaling responses under B deficiency, This work was supported by the MINECO BIO2012-32796 Spanish grant, the Juan de la Cierva Fellowship Program (JCI-2012-14172) (MINECO, Spain) (to M.R), the Postgraduate Studies Scholarship Programme (UAM, Spain) (to L.P.V.) and the FPU Fellowship Program (AP2010-4786) (MECD, Spain) (to I.A)

PROBAC REIPI/GEIH-SEIMC/SAEI Group., The epidemiology of bloodstream infections (BSIs) is dynamic as it depends on microbiological, host and healthcare system factors. The aim of this study was to update the information regarding the epidemiology of BSIs in Spain considering the type of acquisition. An observational, prospective cohort study in 26 Spanish hospitals from October 2016 through March 2017 including all episodes of BSI in adults was performed. Bivariate analyses stratified by type of acquisition were performed. Multivariate analyses were performed by logistic regression. Overall, 6345 BSI episodes were included; 2510 (39.8%) were community-acquired (CA), 1661 (26.3%) were healthcare-associated (HCA) and 2056 (32.6%) hospital-acquired (HA). The 30-day mortality rates were 11.6%, 19.5% and 22.0%, respectively. The median age of patients was 71 years (interquartile range 60–81 years) and 3656 (58.3%; 95% confidence interval 57.1–59.6%) occurred in males. The proportions according to patient sex varied according to age strata. Escherichia coli (43.8%), Klebsiella spp. (8.9%), Staphylococcus aureus (8.9%) and coagulase-negative staphylococci (7.4%) were the most frequent pathogens. Multivariate analyses confirmed important differences between CA and HCA episodes, but also between HCA and HA episodes, in demographics, underlying conditions and aetiology. In conclusion, we have updated the epidemiological information regarding patients’ profiles, underlying conditions, frequency of acquisition types and aetiological agents of BSI in Spain. HCA is confirmed as a distinct type of acquisition., This work was financed by grants from Plan Nacional de I+D+i 2013–2016, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades [PI16/01432] and the Spanish Network for Research in Infectious Diseases (REIPI) [RD16/0016/0001; RD16/0016/0008], co‐financed by the European Development Regional Fund ‘A way to achieve Europe’, Operative program Intelligent Growth 2014–2020.

Boron (B) deficiency affects the development of Pisum sativum nodules and Arabidopsis thaliana root meristems. Both organs show an alteration of cell differentiation that result in the development of tumor-like structures. The fact that B in plants is not only able to interact with components of the cell wall but also with membrane-associated glycoconjugates, led us to analyze changes in high mannose type N-glycans (HMNG). The affinoblots with concanavalin A revealed alterations in the N-glycosylation pattern during early development of nodules and roots under B deprivation. Besides, there is increasing evidence of a B role in animal physiology that brought us to investigate the impact of B deficiency on Danio rerio (zebrafish) development. When B deficiency was induced prior to early cleavage stages, embryos developed as an abnormal undifferentiated mass of cells. Additionally, when B was removed at post-hatching, larvae undergo aberrant organogenesis. Resembling the phenomenon described in plants, alteration of the N-glycosylation pattern occurred in B-deficient zebrafish larvae prior to organogenesis. Overall, these results support a common function of B in plants and animals associated with glycosylation that might be important for cell signaling and cell fate determination during development.

Quinoa has been highlighted as a promising crop to sustain food security. The selection of physiological traits that allow identification genotypes with high Nitrogen use efficiency (NUE) is a key factor to increase Quinoa cultivation. In order to unveil the underpinning mechanisms for N-stress tolerance in Quinoa, three genotypes with similar phenology, but different NUE were developed under high (HN) or low (LN) nitrogen conditions. N metabolism processes and photosynthetic performance were studied after anthesis and in correlation with productivity to identify principal traits related to NUE. We found that protein content, net photosynthesis and leaf dry-mass were determinant attributes for yield at both HN and LN conditions. Contrastingly, the enhancement of N related metabolites ($${{\rm{NH}}}_{4}^{+}$$ NH 4 + , proline, betacyanins) and processes related with re-assimilation of $${{\rm{NH}}}_{4}^{+}$$ NH 4 + , including an increment of glutamine synthetase activity and up-regulation of CqAMT1,1 transporter expression in leaves, were negatively correlated with grain yield at both N conditions. Biochemical aspects of photosynthesis and root biomass were traits exclusively associated with grain yield at LN. The impact of N supply on seed quality is discussed. These results provide new insights towards the understanding the N metabolism of Quinoa.