Morphological and genetic diversity of maize landraces along an altitudinal gradient in the Southern Andes

Maize (Zea mays ssp. mays) is a major cereal crop worldwide and is traditionally or commercially cultivated almost all over the Americas. The northwestern region of Argentina (NWA) constitutes one of the main diversity hotspots of the Southern Andes, with contrasting landscapes and a large number of landraces. Despite the extensive collections performed by the “Banco Activo de Germoplasma INTA Pergamino, Argentina” (BAP), most of them have not been characterized yet. Here we report the morphological and molecular evaluation of 30 accessions collected from NWA, along an altitudinal gradient between 1120 and 2950 meters above sea level (masl). Assessment of morphological variation in a common garden allowed the discrimination of two groups, which differed mainly in endosperm type and overall plant size. Although the groups retrieved by the molecular analyses were not consistent with morphological clusters, they showed a clear pattern of altitudinal structuring. Affinities among accessions were not in accordance with racial assignments. Overall, our results revealed that there are two maize gene pools co-existing in NWA, probably resulting from various waves of maize introduction in pre-Columbian times as well as from the adoption of modern varieties by local farmers. In conclusion, the NWA maize landraces preserved at the BAP possess high morphological and molecular variability. Our results highlight their potential as a source of diversity for increasing the genetic basis of breeding programs and provide useful information to guide future sampling and conservation efforts.EEA PergaminoFil: Rivas, Juan Gabriel. Instituto Nacional de Tecnología Agropecuaria-Consejo Nacional de Investigaciones Científicas y Técnicas (INTA-CONICET). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); ArgentinaFil: Gutiérrez, Ángela V. Instituto Nacional de Tecnología Agropecuaria-Consejo Nacional de Investigaciones Científicas y Técnicas (INTA-CONICET). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); ArgentinaFil: Defacio, Raquel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Recursos Genéticos; ArgentinaFil: Schimpf, Jorge. Universidad Nacional de Jujuy. Facultad de Ciencias Agrarias; ArgentinaFil: Vicario, Ana L. Instituto Nacional de Semillas (INASE). Laboratorio de Marcadores Moleculares y Fitopatología; ArgentinaFil: Hopp, H. Esteban. Instituto Nacional de Tecnología Agropecuaria-Consejo Nacional de Investigaciones Científicas y Técnicas (INTA-CONICET). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); ArgentinaFil: Hopp, H. Esteban. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Paniego, Norma Beatriz. Instituto Nacional de Tecnología Agropecuaria-Consejo Nacional de Investigaciones Científicas y Técnicas (INTA-CONICET). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); ArgentinaFil: Lia, Veronica V. Instituto Nacional de Tecnología Agropecuaria-Consejo Nacional de Investigaciones Científicas y Técnicas (INTA-CONICET). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); ArgentinaFil: Lia, Veronica V. Esteban. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentin

Carotenoides en agroalimentación y salud

Los carotenoides son compuestos especiales; si bien es común referirse a ellos como pigmentos, lo cierto es que son compuestos de gran versatilidad e importancia en la naturaleza. Más específicamente, son de gran interés en agroalimentación y salud. Así, por ejemplo, son pigmentos naturales y por lo tanto tienen un importante papel en la elección de alimentos por parte de los consumidores. Asimismo, algunos de ellos son precursores de la vitamina A. Sin embargo, que cada vez exista más interés en los carotenoides en este contexto se debe en gran parte a muchos estudios de distinta naturaleza que indican que pueden proporcionar beneficios para la salud. Su interés en alimentación funcional es por lo tanto indudable. En este libro se refleja la experiencia en carotenoides de un gran número de profesionales de la región iberoamericana. En conjunto, se ofrece una visión general de la investigación sobre estos compuestos en agroalimentación y salud. Los autores son miembros de la red IBERCAROT (http://carotenoides.us.es), que tiene entre sus objetivos conformar una red estable y funcional de profesionales que aúnen esfuerzos en pos de identificar nuevas fuentes de carotenoides de interés nutricional, mejorar su producción y aumentar el valor de los productos que los contengan

miR-16 and miR-125b are involved in barrier function dysregulation through the modulation of claudin-2 and cingulin expression in the jejunum in IBS with diarrhoea

Micro-RNAs (miRNAs) play a crucial role in controlling intestinal epithelial barrier function partly by modulating the expression of tight junction (TJ) proteins. We have previously shown differential messenger RNA (mRNA) expression correlated with ultrastructural abnormalities of the epithelial barrier in patients with diarrhoea-predominant IBS (IBS-D). However, the participation of miRNAs in these differential mRNA-associated findings remains to be established. Our aims were (1) to identify miRNAs differentially expressed in the small bowel mucosa of patients with IBS-D and (2) to explore putative target genes specifically involved in epithelial barrier function that are controlled by specific dysregulated IBS-D miRNAs. Healthy controls and patients meeting Rome III IBS-D criteria were studied. Intestinal tissue samples were analysed to identify potential candidates by: (a) miRNA-mRNA profiling; (b) miRNA-mRNA pairing analysis to assess the co-expression profile of miRNA-mRNA pairs; (c) pathway analysis and upstream regulator identification; (d) miRNA and target mRNA validation. Candidate miRNA-mRNA pairs were functionally assessed in intestinal epithelial cells. IBS-D samples showed distinct miRNA and mRNA profiles compared with healthy controls. TJ signalling was associated with the IBS-D transcriptional profile. Further validation of selected genes showed consistent upregulation in 75% of genes involved in epithelial barrier function. Bioinformatic analysis of putative miRNA binding sites identified hsa-miR-125b-5p and hsa-miR-16 as regulating expression of the TJ genes CGN (cingulin) and CLDN2 (claudin-2), respectively. Consistently, protein expression of CGN and CLDN2 was upregulated in IBS-D, while the respective targeting miRNAs were downregulated. In addition, bowel dysfunction, perceived stress and depression and number of mast cells correlated with the expression of hsa-miR-125b-5p and hsa-miR-16 and their respective target proteins. Modulation of the intestinal epithelial barrier function in IBS-D involves both transcriptional and post-transcriptional mechanisms. These molecular mechanisms include miRNAs as master regulators in controlling the expression of TJ proteins and are associated with major clinical symptoms

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

HIF-1 and c-Src Mediate Increased Glucose Uptake Induced by Endothelin-1 and Connexin43 in Astrocytes

In previous work we showed that endothelin-1 (ET-1) increases the rate of glucose uptake in astrocytes, an important aspect of brain function since glucose taken up by astrocytes is used to supply the neurons with metabolic substrates. In the present work we sought to identify the signalling pathway responsible for this process in primary culture of rat astrocytes. Our results show that ET-1 promoted an increase in the transcription factor hypoxia-inducible factor-1α (HIF-1α) in astrocytes, as shown in other cell types. Furthermore, HIF-1α-siRNA experiments revealed that HIF-1α participates in the effects of ET-1 on glucose uptake and on the expression of GLUT-1, GLUT-3, type I and type II hexokinase. We previously reported that these effects of ET-1 are mediated by connexin43 (Cx43), the major gap junction protein in astrocytes. Indeed, our results show that silencing Cx43 increased HIF-1α and reduced the effect of ET-1 on HIF-1α, indicating that the effect of ET-1 on HIF-1α is mediated by Cx43. The activity of oncogenes such as c-Src can up-regulate HIF-1α. Since Cx43 interacts with c-Src, we investigated the participation of c-Src in this pathway. Interestingly, both the treatment with ET-1 and with Cx43-siRNA increased c-Src activity. In addition, when c-Src activity was inhibited neither ET-1 nor silencing Cx43 were able to up-regulate HIF-1α. In conclusion, our results suggest that ET-1 by down-regulating Cx43 activates c-Src, which in turn increases HIF-1α leading to the up-regulation of the machinery required to take up glucose in astrocytes. Cx43 expression can be reduced in response not only to ET-1 but also to various physiological and pathological stimuli. This study contributes to the identification of the signalling pathway evoked after Cx43 down-regulation that results in increased glucose uptake in astrocytes. Interestingly, this is the first evidence linking Cx43 to HIF-1, which is a master regulator of glucose metabolism

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Haploidentical transplantation in pediatric non-malignant diseases: A retrospective analysis on behalf of the Spanish Group for Hematopoietic Transplantation (GETH)

[Objective]: Describe the GETH haploidentical stem cell transplantation (haplo‐HSCT) activity in non‐malignant disease (NMDs).[Methods]: We retrospectively analyzed data from children with NMDs who underwent haplo‐HSCT.[Results]: From January 2001 to December 2016, 26 pediatric patients underwent 31 haplo‐HSCT through ex vivo T cell‐depleted (TCD) graft platforms or post‐transplantation cyclophosphamide (PT‐Cy) at 7 Spanish centers. Five cases employed unmanipulated PT‐Cy haplo‐HSCT, 16 employed highly purified CD34+ cells, and 10 employed ex vivo TCD grafts manipulated either with CD3+CD19+ depletion, TCRαβ+CD19+ selection or naive CD45RA+ T‐cell depletion. Peripheral blood stem cells were the sole source for patients following TCD haplo‐HSCT, and bone marrow was the source for one PT‐Cy haplo‐HSCT. The most common indications for transplantation were primary immunodeficiency disorders (PIDs), severe aplastic anemia, osteopetrosis, and thalassemia. The 1‐year cumulative incidence of graft failure was 27.4%. The 1‐year III‐IV acute graft‐versus‐host disease (GvHD) and 1‐year chronic GvHD rates were 34.6% and 16.7%, respectively. The 2‐year overall survival was 44.9% for PIDs, and the 2‐year graft‐versus‐host disease‐free and relapse‐free survival rate was 37.6% for the other NMDs. The transplantation‐related mortality at day 100 was 30.8%.[Conclusion]: Although these results are discouraging, improvements will come if procedures are centralized in centers of expertise.This work was supported in part by the National Health Service of Spain, Carlos III Health Institute (ISCIII), FONDOS FEDER grant (FIS) PI18/01301, the CRIS Cancer Foundation (http://criscancer.org), and the Association Pablo Ugarte (http://www.asociacionpablougarte.es/)

Carotenoides en agroalimentación y salud

Los carotenoides son compuestos especiales; si bien es común referirse a ellos como pigmentos, lo cierto es que son compuestos de gran versatilidad e importancia en la naturaleza. Más específicamente, son de gran interés en agroalimentación y salud. Así, por ejemplo, son pigmentos naturales y por lo tanto tienen un importante papel en la elección de alimentos por parte de los consumidores. Asimismo, algunos de ellos son precursores de la vitamina A. Sin embargo, que cada vez exista más interés en los carotenoides en este contexto se debe en gran parte a muchos estudios de distinta naturaleza que indican que pueden proporcionar beneficios para la salud. Su interés en alimentación funcional es por lo tanto indudable. En este libro se refleja la experiencia en carotenoides de un gran número de profesionales de la región iberoamericana. En conjunto, se ofrece una visión general de la investigación sobre estos compuestos en agroalimentación y salud. Los autores son miembros de la red ibercarot (http://carotenoides.us.es), que tiene entre sus objetivos conformar una red estable y funcional de profesionales que aúnen esfuerzos en pos de identificar nuevas fuentes de carotenoides de interés nutricional, mejorar su producción y aumentar el valor de los productos que los contengan. Me gustaría agradecer a todas y cada una de las personas que han contribuido de una u otra forma a que este libro sea una realidad. Todos esperamos que sea de ayuda para personas interesadas en los temas desarrollados. Gracias especialmente al Programa Iberoamericano de Ciencia y Tecnología para el Desarrollo (Cyted, http:// www.cyted.org/) que, con su apoyo económico a la red ibercarot, ha hecho posible que varias decenas de equipos interaccionen en torno a temas de interés común para contribuir al desarrollo a distintos niveles de la región iberoamericana.RED TEMÁTICA IBERCAROT (referencia 112RT445) http://carotenoides.us.es PROGRAMA IBEROAMERICANO DE CIENCIA Y TECNOLOGIA PARA EL DESARROLLO – CYTEDPeer reviewe

miR-16 and miR-125b are involved in barrier function dysregulation through the modulation of claudin-2 and cingulin expression in the jejunum in IBS with diarrhoea

Micro-RNAs (miRNAs) play a crucial role in controlling intestinal epithelial barrier function partly by modulating the expression of tight junction (TJ) proteins. We have previously shown differential messenger RNA (mRNA) expression correlated with ultrastructural abnormalities of the epithelial barrier in patients with diarrhoea-predominant IBS (IBS-D). However, the participation of miRNAs in these differential mRNA-associated findings remains to be established. Our aims were (1) to identify miRNAs differentially expressed in the small bowel mucosa of patients with IBS-D and (2) to explore putative target genes specifically involved in epithelial barrier function that are controlled by specific dysregulated IBS-D miRNAs. Healthy controls and patients meeting Rome III IBS-D criteria were studied. Intestinal tissue samples were analysed to identify potential candidates by: (a) miRNA-mRNA profiling; (b) miRNA-mRNA pairing analysis to assess the co-expression profile of miRNA-mRNA pairs; (c) pathway analysis and upstream regulator identification; (d) miRNA and target mRNA validation. Candidate miRNA-mRNA pairs were functionally assessed in intestinal epithelial cells. IBS-D samples showed distinct miRNA and mRNA profiles compared with healthy controls. TJ signalling was associated with the IBS-D transcriptional profile. Further validation of selected genes showed consistent upregulation in 75% of genes involved in epithelial barrier function. Bioinformatic analysis of putative miRNA binding sites identified hsa-miR-125b-5p and hsa-miR-16 as regulating expression of the TJ genes CGN (cingulin) and CLDN2 (claudin-2), respectively. Consistently, protein expression of CGN and CLDN2 was upregulated in IBS-D, while the respective targeting miRNAs were downregulated. In addition, bowel dysfunction, perceived stress and depression and number of mast cells correlated with the expression of hsa-miR-125b-5p and hsa-miR-16 and their respective target proteins. Modulation of the intestinal epithelial barrier function in IBS-D involves both transcriptional and post-transcriptional mechanisms. These molecular mechanisms include miRNAs as master regulators in controlling the expression of TJ proteins and are associated with major clinical symptoms

Rationale for combined therapies in severe-to-critical COVID-19 patients

An unprecedented global social and economic impact as well as a significant number of fatalities have been brought on by the coronavirus disease 2019 (COVID-19), produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Acute SARS-CoV-2 infection can, in certain situations, cause immunological abnormalities, leading to an anomalous innate and adaptive immune response. While most patients only experience mild symptoms and recover without the need for mechanical ventilation, a substantial percentage of those who are affected develop severe respiratory illness, which can be fatal. The absence of effective therapies when disease progresses to a very severe condition coupled with the incomplete understanding of COVID-19’s pathogenesis triggers the need to develop innovative therapeutic approaches for patients at high risk of mortality. As a result, we investigate the potential contribution of promising combinatorial cell therapy to prevent death in critical patients.This research was funded by the financial support to BS from: Institute of Health Carlos III (Co-funded by Fondos FEDER), Project ICI21/00016 and Agencia Valenciana de Innovacion Projects AVI-GVA COVID-19-68 and GVA-COVI19/2021/047 and Project JDRF 2-SRA-2019-837