The begomovirus Tomato leaf curl New Delhi virus is not seed-transmitted in melon

Transmission of plant viruses through seed can be one of the major factors contributing to long- distance dispersal through global trade of seeds and can have important ecological consequences for virus dissemination. Begomoviruses (genus Begomovirus, family Geminiviridae), and among them isolates of the species Tomato leaf curl New Delhi virus (ToLCNDV), cause significant yield losses in economically important crops worldwide. These viruses are horizontally transmitted in nature in a circulative and persistent manner by the whitefly Bemisia tabaci but in recent years several reports have raised the possibility of vertical transmission through seeds for some members of this genus. We have investigated the possible transmission by melon (Cucumis melo L.) seeds of a ToLCNDV isolate of the “Spain” strain, in three different melon cultivars (all susceptible to ToLCNDV). The presence of ToLCNDV in floral tissues and the detection of viral DNA in seeds reveals the seed-borne nature of this virus. However, grow-out studies conducted with the progeny of melon plants germinated from seeds collected from ToLCNDV-infected plants and evaluated at early (1 leaf) or at late (20 leaves) growth stages did not support the vertical transmission of ToLCNDV from seeds to the offspring.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

The begomovirus tomato leaf curl New Delhi virus is not seed-transmitted in melon

Transmission of plant viruses through seed can be one of the major factors contributing to longdistance dispersal through global trade of seeds and can have important ecological consequences for virus dissemination. Begomoviruses (genus Begomovirus, family Geminiviridae), and among them isolates of the species Tomato leaf curl New Delhi virus (ToLCNDV), cause significant yield losses in economically important crops worldwide. These viruses are horizontally transmitted in nature in a circulative and persistent manner by the whitefly Bemisia tabaci but in recent years several reports have raised the possibility of vertical transmission through seeds for some members of this genus. We have investigated the possible transmission by melon (Cucumis melo L.) seeds of a ToLCNDV isolate of the “Spain” strain, in three different melon cultivars (all susceptible to ToLCNDV). The presence of ToLCNDV in floral tissues and the detection of viral DNA in seeds reveals the seed-borne nature of this virus. However, grow-out studies conducted with the progeny of melon plants germinated from seeds collected from ToLCNDV-infected plants and evaluated at early (1 leaf) or at late (20 leaves) growth stages did not support the vertical transmission of ToLCNDV from seeds to the offspring.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Seed oil content and composition of Jatropha curcas (L.) and grafted Jatropha curcas (L.) on Jatropha cinerea (Ortega) Muell. Arg. rootstock

Jatropha curcas has been investigated for its high content of oil, its moderate salinity and drought tolerance, and Jatropha cinerea is a species that can withstand long drought periods and tolerate salinity up to 100 mM of NaCl. The aim of this study was to graft J. curcas plants on J. cinerea and grow them in experimental semiarid conditions, different soil and climate conditions from those of J. curcas native area to analyze their effects on oil seed composition and content. The survival of grafted J. curcas on J. cinerea rootstock was 95%. Seeds from grafted and non-grafted plants were analyzed to determine their oil content. The grafted plants showed greater height (150.7 cm) and oil content (51.3%) than the non-grafted plants (123.5 cm and 49.2%, respectively) without affecting their fatty acid composition. The meteorological information of the experimental plot (Baja California Sur, Mexico) showed values below those necessary for good phenological development; nonetheless, the graft improved its characteristics. Therefore, the use of grafted plants is an option for the establishment of J. curcas plantations in other parts of the world with different soil and climate conditions than those where they grow in the wild.Jatropha curcas has been investigated for its high content of oil, its moderate salinity and drought tolerance, and Jatropha cinerea is a species that can withstand long drought periods and tolerate salinity up to 100 mM of NaCl. The aim of this study was to graft J. curcas plants on J. cinerea and grow them in experimental semiarid conditions, different soil and climate conditions from those of J. curcas native area to analyze their effects on oil seed composition and content. The survival of grafted J. curcas on J. cinerea rootstock was 95%. Seeds from grafted and non-grafted plants were analyzed to determine their oil content. The grafted plants showed greater height (150.7 cm) and oil content (51.3%) than the non-grafted plants (123.5 cm and 49.2%, respectively) without affecting their fatty acid composition. The meteorological information of the experimental plot (Baja California Sur, Mexico) showed values below those necessary for good phenological development; nonetheless, the graft improved its characteristics. Therefore, the use of grafted plants is an option for the establishment of J. curcas plantations in other parts of the world with different soil and climate conditions than those where they grow in the wild

Design and synthesis of Mannich base-type derivatives containing imidazole and benzimidazole as lead compounds for drug discovery in Chagas Disease.

The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease, the most important parasitic infection in Latin America. The only treatments currently available are nitro-derivative drugs that are characterised by high toxicity and limited efficacy. Therefore, there is an urgent need for more effective, less toxic therapeutic agents. We have previously identified the potential for Mannich base derivatives as novel inhibitors of this parasite. To further explore this family of compounds, we synthesised a panel of 69 new analogues, based on multi-parametric structure-activity relationships, which allowed optimization of both anti-parasitic activity, physicochemical parameters and ADME properties. Additionally, we optimized our in vitro screening approaches against all three developmental forms of the parasite, allowing us to discard the least effective and trypanostatic derivatives at an early stage. We ultimately identified derivative 3c, which demonstrated excellent trypanocidal properties, and a synergistic mode of action against trypomastigotes in combination with the reference drug benznidazole. Both its druggability and low-cost production make this derivative a promising candidate for the preclinical, in vivo assays of the Chagas disease drug-discovery pipeline

Role of Thioredoxin-1 on Myocardial Stunning in Transgenic Mice

Introducción: La disfunción ventricular posisquémica (miocardio atontado) involucra un aumento del estrés oxidativo. En este sentido, la célula cuenta con mecanismos de defensa, como la tiorredoxina-1, un antioxidante que protege al miocardio de la lesión por isquemia/reperfusión, reduciendo el tamaño del infarto. Objetivo: Evaluar el comportamiento de la función ventricular sistólica y diastólica, particularmente estudiando la rigidez miocárdica y la relajación isovolúmica en el miocardio atontado en diferentes ratones transgénicos. Material y métodos: Se utilizaron corazones de ratones que sobreexpresan tiorredoxina-1 y de ratones transgénicos que sobreexpresan tiorredoxina-1 mutada en su sitio activo (dominante negativo), comparados con los de ratones no transgénicos, los cuales fueron sometidos a 15 minutos de isquemia global y 30 minutos de reperfusión utilizando la técnica de Langendorff. Se evaluó la función ventricular sistólica y diastólica y se calculó el t63 y el t93 como índice de relajación isovolúmica. Resultados: Las mediciones a los 30 minutos de reperfusión mostraron una mejoría significativa del estado contráctil en los ratones tiorredoxina-1 (57,4 ± 4,9 mm Hg; p ≤ 0,05 vs. no transgénicos) y también en la rigidez (11,8 ± 2,9 mm Hg; p ≤ 0,05 vs. no transgénicos). Por otra parte, en los ratones dominantes negativos se observó un aumento de la rigidez (37,7 ± 5,5 mm Hg; p ≤ 0,05 vs. no transgénicos) y un enlentecimiento de la relajación a los 30 minutos de la reperfusión (78,2 ± 9,8 mseg; p ≤ 0,05 vs. no transgénicos). Conclusión: Este trabajo evidencia el rol protector de la tiorredoxina-1 en el miocardio atontado y su importancia fisiopatológica en ratones que sobreexpresan este antioxidante.Background: Postischemic ventricular dysfunction (myocardial stunning) involves increased oxidative stress. In this sense, the cell has defense mechanisms, as thioredoxin-1, an antioxidant that protects the myocardium from ischemia/reperfusion injury, reducing infarct size. Objective: The aim of this study was to evaluate systolic and diastolic ventricular function, specifically analyzing myocardial stiffness and isovolumic relaxation, during myocardial stunning in different transgenic mice. Methods: Hearts from mice overexpressing thioredoxin-1 and transgenic mice overexpressing thioredoxin-1 with gene mutation in its active site (dominant negative) were compared with hearts from non-transgenic mice after 15-minute global ischemia and 30-minute reperfusion using the Langendorff technique. Systolic and diastolic ventricular function was evaluated and t63 and t93 were calculated as ventricular relaxation index. Results: At 30-minute reperfusion, thioredoxin-1 mice showed a significantly improved contractile state (57.4±4.9 mmHg; p≤0.05 vs. non-transgenic mice) and stiffness (11.8±2.9 mmHg; p≤0.05 vs. non-transgenic mice). Conversely, at the same reperfusion time, dominant negative mice exhibited increased stiffness (37.7±5.5 mmHg; p≤0.05 vs. non-transgenic mice) and slower relaxation (78.2±9.8 ms; p≤0.05 vs. non-transgenic mice). Conclusion: This study reveals the protective role of thioredoxin-1 on myocardial stunning and its pathophysiological importance in mice overexpressing this antioxidant.Fil: Mazo, Tamara. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; ArgentinaFil: Pérez, María Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; ArgentinaFil: Gómez, Aldana Anabella. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; ArgentinaFil: Llamosas, María Clara. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; ArgentinaFil: Valdez, Laura Batriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Zaobornyj, Tamara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Nicolosi, Liliana N.. Hospital Español de Buenos Aires;Fil: Rubio, María Cristina. Hospital Español de Buenos Aires;Fil: D'Anunzio, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; ArgentinaFil: Gelpi, Ricardo Jorge. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentin

Association of HLA-B*41:02 with Henoch-Schönlein Purpura (IgA Vasculitis) in Spanish individuals irrespective of the HLA-DRB1 status

INTRODUCTION: To determine whether the human leukocyte antigen (HLA) B alleles are implicated in the susceptibility to Henoch-Schönlein purpura (HSP) in the largest series of Caucasian HSP patients ever assessed for genetic studies. METHODS: The study population was composed of 349 Spanish patients diagnosed with HSP fulfilling the American College of Rheumatology and the Michel et al. classification criteria, and 335 sex and ethnically matched controls. HLA-B phenotypes were determined by sequencing-based typing (SBT) and analyzed by chi-square or Fisher exact test. RESULTS: A statistically significant increase of HLA-B*41:02 allele in HSP patients when compared with controls was found (8.3% versus 1.5% respectively; p = 0.0001; OR (odds ratio) =5.76 [2.15-19.3]). These results remained statistically significant after adjusting for Bonferroni correction (p = 0.0028). An internal validation also confirmed the susceptibility effect on HSP associated with HLA-B*41:02 (OR = 5.70 [1.98-16.44]). Since a former study described an association between HLA-DRB1*01:03 and HSP susceptibility, we also evaluated the implication of HLA-B*41:02 independently of HLA-DRB1*01:03. Interestingly, the association remained statistically significant (p = 0.0004, OR = 4.97 [1.8-16.9]). No HLA-B association with specific HSP clinical features was found. CONCLUSIONS: Our study indicates that HLA-B*41:02 is associated with the susceptibility to HSP in Spanish patients irrespective of HLA-DRB1 status

Role of the IL33 and IL1RL1 pathway in the pathogenesis of Immunoglobulin A vasculitis

Cytokines signalling pathway genes are crucial factors of the genetic network underlying the pathogenesis of Immunoglobulin-A vasculitis (IgAV), an inflammatory vascular condition. An influence of the interleukin (IL)33- IL1 receptor like (IL1RL)1 signalling pathway on the increased risk of several immune-mediated diseases has been described. Accordingly, we assessed whether the IL33-IL1RL1 pathway represents a novel genetic risk factor for IgAV. Three tag polymorphisms within IL33 (rs3939286, rs7025417 and rs7044343) and three within IL1RL1 (rs2310173, rs13015714 and rs2058660), that also were previously associated with several inflammatory diseases, were genotyped in 380 Caucasian IgAV patients and 845 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when IL33 and IL1RL1 variants were analysed independently. Likewise, no statistically significant differences were found in IL33 or IL1RL1 genotype and allele frequencies when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when IL33 and IL1RL1 haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that the IL33-IL1RL1 signalling pathway does not contribute to the genetic network underlying IgAV.Acknowledgements: We are indebted to the patients and healthy controls for their essential collaboration to this study. We also thank the National DNA Bank Repository (Salamanca) for supplying part of the control samples. This study was supported by European Union FEDER funds and `Fondo de Investigaciones Sanitarias´ (Grant PI18/00042) from ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain). DP-P is a recipient of a Río Hortega programme fellowship from the ISCIII, co-funded by the European Social Fund (ESF, `Investing in your future´) (Grant Number CM20/00006). SR-M is supported by funds of the RETICS Program (RD16/0012/0009) (ISCIII, cofunded by the European Regional Development Fund (ERDF)). VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL 18/01). BA-M is a recipient of a `López Albo´ Post-Residency Programme funded by Servicio Cántabro de Salud. LL-G is supported by funds from IDIVAL (INNVAL20/06). OG is staff personnel of Xunta de Galicia (Servizo Galego de Saude (SERGAS)) through a research-staff stabilization contract (ISCIII/SERGAS) and his work is funded by ISCIII and the European Union FEDER fund (Grant Numbers RD16/0012/0014 (RIER) and PI17/00409). He is beneficiary of project funds from the Research Executive Agency (REA) of the European Union in the framework of MSCA-RISE Action of the H2020 Programme, project 734899—Olive-Net. RL-M is a recipient of a Miguel Servet type I programme fellowship from the ISCIII, co-funded by ESF (`Investing in your future´) (Grant Number CP16/00033)

HLA-DRB1 association with Henoch-Schonlein purpura

Objective: Henoch-Schönlein purpura (HSP) is the most common vasculitis in children but it is not exceptional in adults. Increased familial occurrence supports a genetic predisposition for HSP. In this context, an association with the human leukocyte antigen-HLA-DRB1*01 phenotype has been suggested in Caucasian individuals with HSP. However, data on the potential association of HSP with HLA-DRB1*01 were based on small case series. To further investigate this issue, we performed HLA-DRB1 genotyping of the largest series of HSP patients ever assessed for genetic studies in Caucasians. Methods: 342 Spanish patients diagnosed with HSP fulfilling the American College of Rheumatology and the Michel et al classification criteria, and 303 sex and ethnically matched controls were assessed. HLA-DRB1 alleles were determined using a PCR-Sequence-Specific-Oligonucleotide Probe (PCR-SSOP) method. Results: A statistically significant increase of HLA-DRB1*01 in HSP patients when compared with controls was found (43% vs 7%, respectively; p<0.001; odds ratio-OR=2.03 [1.43-2.87]). It was due to the increased frequency of HLA-DRB1*0103 phenotype in HSP (14% vs 2%; p<0.001; OR=8.27 [3.46-23.9]). These results remained statistically significant after adjusting for Bonferroni correction. In contrast, a statistically significant decreased frequency of the HLA-DRB1*0301 phenotype was observed in patients compared to controls (5.6% vs 18.1%, respectively; p<0.001, OR=0.26 [0.14-0.47]), even after adjustment for Bonferroni correction. No HLA-DRB1 association with specific features of the disease was found. Conclusion: Our study confirms an association of HSP with HLA-DRB1*01 in Caucasians. Also, a protective effect against the development of HSP appears to exist in Caucasians carrying the HLA-DRB1*03 phenotype

Mucosal Immune Defence Gene Polymorphisms as Relevant Players in the Pathogenesis of IgA Vasculitis?

ITGAM&ndash;ITGAX (rs11150612, rs11574637), VAV3 rs17019602, CARD9 rs4077515, DEFA (rs2738048, rs10086568), and HORMAD2 rs2412971 are mucosal immune defence polymorphisms, that have an impact on IgA production, described as risk loci for IgA nephropathy (IgAN). Since IgAN and Immunoglobulin-A vasculitis (IgAV) share molecular mechanisms, with the aberrant deposit of IgA1 being the main pathophysiologic feature of both entities, we assessed the potential influence of the seven abovementioned polymorphisms on IgAV pathogenesis. These seven variants were genotyped in 381 Caucasian IgAV patients and 997 matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of these seven polymorphisms when the whole cohort of IgAV patients and those with nephritis were compared to controls. Similar genotype and allele frequencies of all polymorphisms were disclosed when IgAV patients were stratified according to the age at disease onset or the presence/absence of gastrointestinal or renal manifestations. Likewise, no ITGAM&ndash;ITGAX and DEFA haplotype differences were observed when the whole cohort of IgAV patients, along with those with nephritis and controls, as well as IgAV patients, stratified according to the abovementioned clinical characteristics, were compared. Our results suggest that mucosal immune defence polymorphisms do not represent novel genetic risk factors for IgAV pathogenesis

Association of HLA-B*41:02 with Henoch-Schönlein Purpura (IgA Vasculitis) in Spanish individuals irrespective of the HLA-DRB1 status

INTRODUCTION: A study was conducted to determine whether the human leukocyte antigen (HLA) B alleles are implicated in the susceptibility to Henoch-Schönlein purpura (HSP) in the largest series of Caucasian HSP patients ever assessed for genetic studies. METHODS: The study population was composed of 349 Spanish patients diagnosed with HSP fulfilling the American College of Rheumatology and the Michel et al. classification criteria, and 335 sex and ethnically matched controls. HLA-B phenotypes were determined by sequencing-based typing (SBT) and analyzed by chi-square or Fisher exact test. RESULTS: A statistically significant increase of HLA-B*41:02 allele in HSP patients when compared with controls was found (8.3% versus 1.5% respectively; P = 0.0001; OR (odds ratio) =5.76 [2.15-19.3]). These results remained statistically significant after adjusting for Bonferroni correction (P = 0.0028). An internal validation also confirmed the susceptibility effect on HSP associated with HLA-B*41:02 (OR = 5.70 [1.98-16.44]). Since a former study described an association between HLA-DRB1*01:03 and HSP susceptibility, we also evaluated the implication of HLA-B*41:02 independently of HLA-DRB1*01:03. Interestingly, the association remained statistically significant (P = 0.0004, OR = 4.97 [1.8-16.9]). No HLA-B association with specific HSP clinical features was found. CONCLUSIONS: Our study indicates that HLA-B*41:02 is associated with the susceptibility to HSP in Spanish patients irrespective of HLA-DRB1 status.This study was supported by a grant from ‘Fondo de Investigaciones Sanitarias’ PI12/00193 (Spain). RLM is a recipient of a Sara Borrell postdoctoral fellowship from the Instituto de Salud Carlos III at the Spanish Ministry of Health (Spain) (CD12/00425). FG and BU are supported by funds from the RETICS Program (RIER) (RD12/0009/0013).Ye