botrytis cinerea induces local hypoxia in arabidopsis leaves

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Multiple bHLH/MYB-based protein complexes regulate proanthocyanidin biosynthesis in the herbage of Lotus spp.

[EN] The environmental impact and health of ruminants fed with forage legumes depend on the herbage's concentration and structure of proanthocyanidins (PAs). Unfortunately, the primary forage legumes (alfalfa and clover) do not contain substantial levels of PAs. No significant progress has been made to induce PAs to agronomically valuable levels in their edible organs by biotechnological approaches thus far. Building this trait requires a profound knowledge of PA regulators and their interplay in species naturally committed to accumulating these metabolites in the target organs. Against this background, we compared the shoot transcriptomes of two inter-fertile Lotus species, namely Lotus tenuis and Lotus corniculatus, polymorphic for this trait, to search for differentially expressed MYB and bHLH genes. We then tested the expression of the above-reported regulators in L. tenuis x L. corniculatus interspecific hybrids, several Lotus spp., and different L. corniculatus organs with contrasting PA levels. We identified a novel MYB activator and MYB-bHLH-based complexes that, when expressed in Nicotiana benthamiana, trans-activated the promoters of L. corniculatus anthocyanidin reductase and leucoanthocyanidin reductase 1 genes. The last are the two critical structural genes for the biosynthesis of PAs in Lotus spp. Competition between MYB activators for the transactivation of these promoters also emerged. Overall, by employing Lotus as a model genus, we refined the transcriptional network underlying PA biosynthesis in the herbage of legumes. These findings are crucial to engineering this trait in pasture legumes.This study was partially supported by CNR (Italy)-CONICET (Argentina) 2021-2022 Bilateral Agreement, by the project Pict 2021-2023 from Agencia de Promocion Cientifica y Tecnologica (Argentina), by Margin Up, funded by the European Union's Horizon research and innovation program GA number no 101082089, and by the Italian Agritech National Research Center funded by the European Union Next-Generation EU (Piano Nazionale di Ripresa e Resilienza (PNRR)- Missione 4 Componente 2, Investitmento 1.4 - D.D. 1032 17/06/2022, CN00000022). In particular, our study represents an original paper related to the Spoke 4 "Multifunctional and resilient agriculture and forestry systems for the mitigation of climate change risks" of the PNRR project. However, views and opinions expressed are those of the authors and do not necessarily reflect those of the European Union or the European Research Agency (REA). Neither the European Union nor the granting authorities can be held responsible. Open access funding provided by Consiglio Nazionale Delle Ricerche (CNR) within the CRUI-CARE Agreement.Escaray, FJ.; Valeri, MC.; Damiani, F.; Ruiz, OA.; Carrasco, P.; Paolocci, F. (2024). Multiple bHLH/MYB-based protein complexes regulate proanthocyanidin biosynthesis in the herbage of Lotus spp. Planta. 259(1). https://doi.org/10.1007/s00425-023-04281-2259

179. Correcting the Bleeding Phenotype in Hemophilia Ausing Lentivirally FVIII-Corrected Endothelial Cells Differentiated from Hemophilic Induced Pluripotent Stem Cell (iPSC)

Hemophilia A (HA) is a bleeding disorder caused by factor VIII (FVIII) gene mutations.Somatic cells can be reprogrammed to generate autologous, disease-free iPSCs, then differentiated into cell targetsrelevant for gene and cell therapy. Our aim is to develop a novel HA treatment strategy generating FVIII-corrected patient-specific iPSCs from peripheral blood cells anddifferentiating them into functional endothelial cells (ECs), secreting FVIII after transplantation

Bioactive compound profiling of olive fruit: the contribution of genotype

The health, therapeutic, and organoleptic characteristics of olive oil depend on functional bioactive compounds, such as phenols, tocopherols, squalene, and sterols. Genotype plays a key role in the diversity and concentration of secondary compounds peculiar to olive. In this study, the most important bioactive compounds of olive fruit were studied in numerous international olive cultivars during two consecutive seasons. A large variability was measured for each studied metabolite in all 61 olive cultivars. Total phenol content varied on a scale of 1–10 (3831–39,252 mg kg1) in the studied cultivars. Squalene values fluctuated over an even wider range (1–15), with values of 274 to 4351 mg kg1. Total sterols ranged from 119 to 969 mg kg1, and total tocopherols varied from 135 to 579 mg kg1 in fruit pulp. In the present study, the linkage among the most important quality traits highlighted the scarcity of cultivars with high content of at least three traits together. This work provided sound information on the fruit metabolite profile of a wide range of cultivars, which will facilitate the studies on the genomic regulation of plant metabolites and development of new olive genotypes through genomics-assisted breeding.EEA San JuanFil: Mousavi, Soraya. National Research Council. Institute of Biosciences and Bioresources; ItaliaFil: Stanzione, Vitale. National Research Council. Institute for Agricultural and Forest Systems of the Mediterranean; ItaliaFil: Mariotti, Roberto. National Research Council. Institute of Biosciences and Bioresources; ItaliaFil: Mastio, Valerio.Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Juan; Argentina.Fil: Mastio, Valerio. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Azariadis, Aristotelis. Mediterranean Agronomic Institute of Chania. Department of Horticultural Genetics and Biotechnology; GreciaFil: Passeri, Valentina. National Research Council. Institute for Agricultural and Forest Systems of the Mediterranean; ItaliaFil: Valeri, Maria Cristina. National Research Council. Institute of Biosciences and Bioresources; ItaliaFil: Baldoni, Luciana. National Research Council. Institute of Biosciences and Bioresources; ItaliaFil: Bufacchi, Marina. National Research Council. Institute for Agricultural and Forest Systems of the Mediterranean; Itali

Upregulation of NKG2D ligands impairs hematopoietic stem cell function in Fanconi anemia

Cellular immune response; Immunology; Stem cellsRespuesta inmune celular; Inmunología; Células madreResposta immune cel·lular; Immunologia; Cèl·lules mareFanconi anemia (FA) is the most prevalent inherited bone marrow failure (BMF) syndrome. Nevertheless, the pathophysiological mechanisms of BMF in FA have not been fully elucidated. Since FA cells are defective in DNA repair, we hypothesized that FA hematopoietic stem and progenitor cells (HSPCs) might express DNA damage–associated stress molecules such as natural killer group 2 member D ligands (NKG2D-Ls). These ligands could then interact with the activating NKG2D receptor expressed in cytotoxic NK or CD8+ T cells, which may result in progressive HSPC depletion. Our results indeed demonstrated upregulated levels of NKG2D-Ls in cultured FA fibroblasts and T cells, and these levels were further exacerbated by mitomycin C or formaldehyde. Notably, a high proportion of BM CD34+ HSPCs from patients with FA also expressed increased levels of NKG2D-Ls, which correlated inversely with the percentage of CD34+ cells in BM. Remarkably, the reduced clonogenic potential characteristic of FA HSPCs was improved by blocking NKG2D–NKG2D-L interactions. Moreover, the in vivo blockage of these interactions in a BMF FA mouse model ameliorated the anemia in these animals. Our study demonstrates the involvement of NKG2D–NKG2D-L interactions in FA HSPC functionality, suggesting an unexpected role of the immune system in the progressive BMF that is characteristic of FA.This work was supported by the “Ministerio de Ciencia e Innovación y Competitividad y Fondo Europeo de Desarrollo Regional (FEDER)” (SAF2015-68073-R, SAF2015-64152-R, and RTI2018-097125-B-I00); Next Generation EU; Plan de Recuperación Transformación y Resilencia (Instituto de Salud Carlos III; TERAV) (RD12/0019/0023); Programs of the European Commission (HEALTHF5-2012-305421 and EUROFANCOLEN); the “Ministerio de Sanidad, Servicios Sociales e Igualdad” (EC11/060 and EC11/550 “Comunidad de Madrid” (AvanCell, B2017/BMD-3692); and the ICREA-Academia program

Molecular mechanisms underlying AMH elevation in hyperoestrogenic states in males

Anti-Müllerian hormone (AMH) is secreted by Sertoli cells of the testes from early fetal life until puberty, when it is downregulated by androgens. In conditions like complete androgen insensitivity syndrome (CAIS), AMH downregulation does not occur and AMH increases at puberty, due in part to follicle-stimulating hormone (FSH) effect. However, other conditions like Peutz-Jeghers syndrome (PJS), characterised by low FSH, also have increased AMH. Because both CAIS and PJS may present as hyperoestrogenic states, we tested the hypothesis that oestradiol (E2) upregulates AMH expression in peripubertal Sertoli cells and explored the molecular mechanisms potentially involved. The results showed that E2 is capable of inducing an upregulation of endogenous AMH and of the AMH promoter activity in the prepubertal Sertoli cell line SMAT1, signalling through ERα binding to a specific ERE sequence present on the hAMH promoter. A modest action was also mediated through the membrane oestrogen receptor GPER. Additionally, the existence of ERα expression in Sertoli cells in patients with CAIS was confirmed by immunohistochemistry. The evidence presented here provides biological plausibility to the hypothesis that testicular AMH production increases in clinical conditions in response to elevated oestrogen levels.Fil: Valeri, Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Lovaisa, María M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Racine, Chrystèle. Inserm; FranciaFil: Edelsztein, Nadia Yasmín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Riggio, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Giulianelli, Sebastian Jesus. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Biología de Organismos Marinos; ArgentinaFil: Venara, Marcela Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Bedecarras, Patricia Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Ballerini, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: di Clemente, Nathalie. Inserm; FranciaFil: Lamb, Caroline Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Schteingart, Helena Fedora. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Rey, Rodolfo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentin

Exploring olive genetic diversity in the Maltese Islands

comprehensive effort was devoted to exploring, collecting and characterizing the local Maltese olive germplasm, often represented by ancient, monumental trees and by plants of uncertain origin. SSR and cp-SSR analysis of all samples enabled the identification of 46 genotypes and establishment of the correspondence between ancient trees, main local varieties and other Mediterranean cultivars. The application of plastid markers enabled identification of two lineages among Maltese genotypes, with more than 50% represented by lineage E2. Twenty-nine cases of grafting were identified among the various genotypes and lineages. In most cases, E1 canopies were grafted on E2 rootstocks, but reverse cases were also observed. The phylogenetic study of Maltese genotypes, together with hundreds of cultivars from the Mediterranean Basin and beyond, highlights the richness of Maltese olive diversity and drawing attention to the genetic similarity of some Maltese olive genotypes with neighboring Italian and Algerian varieties. These results underline the long-lasting presence of the olive in the country, contributing to the reconstruction of its phylogeny and demonstrating a possible autochthonous origin of many samples. Some still-living ancient trees are at serious risk of extinction due to abandonment, urban expansion and environmental threats. This study supports the preservation of the Maltese olive germplasm and highlights its importance as a rich genetic source to face new agronomical challenges and future climatic constraints.This research was funded by GAL XLOKK of Malta as a part of Measure 19.3 of the EU LEADER Program 2014–2020.peer-reviewe

Autism Spectrum Disorder and Early Psychosis: a narrative review from a neurodevelopmental perspective

Autism Spectrum Disorder (ASD), characterized by socio-communicative abnormalities and restricted, repetitive, and stereotyped behaviors, is part of Neurodevelopmental Disorders (NDDs), a diagnostic category distinctly in accordance with the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, (DSM-5), clearly separated from Schizophrenia Spectrum Disorder (SSD) (schizophrenia, schizophreniform disorder, schizoaffective disorder, schizotypal personality disorder). Over the last four decades, this clear distinction is gradually being replaced, describing ASD and SSD as two heterogeneous conditions but with neurodevelopmental origins and overlaps. Referring to the proposal of a neurodevelopmental continuum model, the current research’s aim is to provide an update of the knowledge to date on the course of clinical symptoms and their overlaps among ASD and SSD. A narrative review of the literature published between January 2010 and June 2023 was conducted. Five studies were included. All studies show a global impairment in both conditions. Two studies show a focus on neurodevelopmental perspective in ASD and SSD. Only one study of these adopts a longitudinal prospective in terms of prognostic markers among ASD and SSD. Three studies underline the overlap between ASD and SSD in terms of negative, disorganized and positive symptomatology. To date, there is a gap in the current scientific literature focused on ASD-SSD course of clinical symptoms and their overlaps from a neurodevelopmental perspective. Future longitudinal studies to identify risk markers and tailored treatments are needed

MicroRNA 193b-3p as a predictive biomarker of chronic kidney disease in patients undergoing radical nephrectomy for renal cell carcinoma

Background: A significant proportion of patients undergoing radical nephrectomy (RN) for clear-cell renal cell carcinoma (RCC) develop chronic kidney disease (CKD) within a few years following surgery. Chronic kidney disease has important health, social and economic impact and no predictive biomarkers are currently available. MicroRNAs (miRs) are small non-coding RNAs implicated in several pathological processes. Methods: Primary objective of our study was to define miRs whose deregulation is predictive of CKD in patients treated with RN. Ribonucleic acid from formalin-fixed paraffin embedded renal parenchyma (cortex and medulla isolated separately) situated >3 cm from the matching RCC was tested for miR expression using nCounter NanoString technology in 71 consecutive patients treated with RN for RCC. Validation was performed by RT–PCR and in situ hybridisation. End point was post-RN CKD measured 12 months post-operatively. Multivariable logistic regression and decision curve analysis were used to test the statistical and clinical impact of predictors of CKD. Results: The overexpression of miR-193b-3p was associated with high risk of developing CKD in patients undergoing RN for RCC and emerged as an independent predictor of CKD. The addition of miR-193b-3p to a predictive model based on clinical variables (including sex and estimated glomerular filtration rate) increased the sensitivity of the predictive model from 81 to 88%. In situ hybridisation showed that miR-193b-3p overexpression was associated with tubule-interstitial inflammation and fibrosis in patients with no clinical or biochemical evidence of pre-RN nephropathy. Conclusions: miR-193b-3p might represent a useful biomarker to tailor and implement surveillance strategies for patients at high risk of developing CKD following RN

Deep phenotyping of the neuroimaging and skeletal features in KBG syndrome: a study of 53 patients and review of the literature

Background: KBG syndrome is caused by haploinsufficiency of ANKRD11and is characterised by macrodontia of upper central incisors, distinctive facial features, short stature, skeletal anomalies, developmental delay, brain malformations and seizures. The central nervous system (CNS) and skeletal features remain poorly defined. Methods: CNS and/or skeletal imaging were collected from molecularly confirmed individuals with KBG syndrome through an international network. We evaluated the original imaging and compared our results with data in the literature. Results: We identified 53 individuals, 44 with CNS and 40 with skeletal imaging. Common CNS findings included incomplete hippocampal inversion and posterior fossa malformations; these were significantly more common than previously reported (63.4% and 65.9% vs 1.1% and 24.7%, respectively). Additional features included patulous internal auditory canal, never described before in KBG syndrome, and the recurrence of ventriculomegaly, encephalic cysts, empty sella and low-lying conus medullaris. We found no correlation between these structural anomalies and epilepsy or intellectual disability. Prevalent skeletal findings comprised abnormalities of the spine including scoliosis, coccygeal anomalies and cervical ribs. Hand X-rays revealed frequent abnormalities of carpal bone morphology and maturation, including a greater delay in ossification compared with metacarpal/phalanx bones. Conclusion: This cohort enabled us to describe the prevalence of very heterogeneous neuroradiological and skeletal anomalies in KBG syndrome. Knowledge of the spectrum of such anomalies will aid diagnostic accuracy, improve patient care and provide a reference for future research on the effects ofANKRD11variants in skeletal and brain development