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1

MORETTI, Samuele, Andrea PACETTI, Romain PIERRON, Hanns-Heinz KASSEMEYER, Michael FISCHER, Jean-Pierre PÉROS, Gabriel PEREZ-GONZALEZ et al. « Fomitiporia mediterranea M. Fisch., the historical Esca agent : a comprehensive review on the main grapevine wood rot agent in Europe ». Phytopathologia Mediterranea 60, no 2 (13 septembre 2021) : 351–79. http://dx.doi.org/10.36253/phyto-13021.

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Fomitiporia mediterranea M. Fisch. (Fmed) is a basidiomycete first described in 2002, and was considered up to then as part of Fomitiporia punctata (P. Karst) Murrill. This fungus can degrade lignocellulosic biomass, causing white rot and leaving bleached fibrous host residues. In Europe Fmed is considered the main grapevine wood rot (Esca) agent within the Esca disease complex, which includes some of the most economically important Grapevine Trunk Diseases (GTDs). This review summarises and evaluates published research on Fmed, on white rot elimination by curettage or management by treatments with specific products applied to diseased grapevines, and on the relationship between wood symptoms and Grapevine Leaf Stripe Disease (GLSD) in the Esca disease complex. Information is also reviewed on the fungus biology, mechanisms of pathogenicity, and their possible relationships with external foliar symptoms of the Esca disease complex. Information on Fmed control strategies is also reviewed.
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Yi, Jia, Shui Bing Xiao, Zhi Xiong Zeng, Jin Fang Lu, Lu Yi Liu, Zubair Ahmed Laghari, Pin Nie, Hong Bing Yu et Hai Xia Xie. « EseE of Edwardsiella tarda Augments Secretion of Translocon Protein EseC and Expression of theescC-eseEOperon ». Infection and Immunity 84, no 8 (6 juin 2016) : 2336–44. http://dx.doi.org/10.1128/iai.00106-16.

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Edwardsiella tardais an important Gram-negative pathogen that employs a type III secretion system (T3SS) to deliver effectors into host cells to facilitate bacterial survival and replication. These effectors are translocated into host cells through a translocon complex composed of three secreted proteins, namely, EseB, EseC, and EseD. The secretion of EseB and EseD requires a chaperone protein called EscC, whereas the secretion of EseC requires the chaperone EscA. In this study, we identified a novel protein (EseE) that also regulates the secretion of EseC. AneseEdeletion mutant secreted much less EseC into supernatants, accompanied by increased EseC levels within bacterial cells. We also demonstrated that EseE interacted directly with EseC in a pulldown assay. Interestingly, EseC, EseE, and EscA were able to form a ternary complex, as revealed by pulldown and gel filtration assays. Of particular importance, the deletion ofeseEresulted in decreased levels of EseB and EseD proteins in both the bacterial pellet and supernatant fraction. Furthermore, real-time PCR assays showed that EseE positively regulated the transcription of the translocon operonescC-eseE, comprisingescC,eseB,escA,eseC,eseD, andeseE. These effects of EseE on the translocon components/operon appeared to have a functional consequence, since the ΔeseEstrain was outcompeted by wild-typeE. tardain a mixed infection in blue gourami fish. Collectively, our results demonstrate that EseE not only functions as a chaperone for EseC but also acts as a positive regulator controlling the expression of the translocon operonescC-eseE, thus contributing to the pathogenesis ofE. tardain fish.
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CLAVERIE, Marion, Martin NOTARO, Florence FONTAINE et Jacques WERY. « Current knowledge on Grapevine Trunk Diseases with complex etiology : a systemic approach ». Phytopathologia Mediterranea 59, no 1 (16 avril 2020) : 29–53. http://dx.doi.org/10.36253/phyto-11150.

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Among all causes of grapevine decline, Grapevine Trunk Diseases (GTDs) are major concerns for grape growers. This paper reviews knowledge and proposes hypotheses on two major GTDs, esca and Botryosphaeria dieback, and assembles a conceptual model. The objective was to collect information into a sequence, from grapevine nursery propagation processes, through foliar symptom expression, to plant death in mature vineyards. Pathogen infection and colonization steps in woody vine tissues, and the hypotheses that have been formulated to explain the outburst of foliar symptoms, are reported and discussed. Factors that could aggravate or repress GTD symptoms and incidence expansion are also addressed. Vine physiology and pathology together could expand understanding of these diseases. Knowledge and hypotheses that need validation are summarized, and a conceptual model is proposed to explain the occurrence of symptoms and the influencing factors. The model could be useful to cope with the complexity of GTDs, and as a starting point for research to unravel knowledge gaps and suggest new disease management strategies.
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Pacetti, Andrea, Samuele Moretti, Catia Pinto, Stéphane Compant, Sibylle Farine, Christophe Bertsch et Laura Mugnai. « Trunk Surgery as a Tool to Reduce Foliar Symptoms in Diseases of the Esca Complex and Its Influence on Vine Wood Microbiota ». Journal of Fungi 7, no 7 (29 juin 2021) : 521. http://dx.doi.org/10.3390/jof7070521.

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In the last few years, trunk surgery has gained increasing attention as a method to reduce foliar symptoms typical of some of the Esca complex diseases. The technique relies on the mechanical removal of decayed wood by a chainsaw. A study on a 14-year-old Cabernet Sauvignon vineyard was carried out to validate the efficacy of trunk surgery and explore possible explanations behind it. Three levels of treatment were applied to three of the most characteristic symptoms associated with some diseases of the Esca complex, such as leaf stripe symptoms (LS), wilted shoots (WS) and apoplexy (APP). The most promising results were obtained by complete trunk surgery, where the larger decay removal allowed lower symptom re-expression. According to the wood types analyzed (decay, medium and sound wood), different changes in microbiota were observed. Alpha-diversity generally decreased for bacteria and increased for fungi. More specifically, main changes were observed for Fomitiporia mediterranea abundance that decreased considerably after trunk surgery. A possible explanation for LS symptom reduction after trunk surgery could be the microbiota shifting caused by the technique itself affecting a microbic-shared biochemical pathway involved in symptom expression.
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Magnin-Robert, Maryline, Marielle Adrian, Sophie Trouvelot, Alessandro Spagnolo, Lucile Jacquens, Patricia Letousey, Fanja Rabenoelina et al. « Alterations in Grapevine Leaf Metabolism Occur Prior to Esca Apoplexy Appearance ». Molecular Plant-Microbe Interactions® 30, no 12 (décembre 2017) : 946–59. http://dx.doi.org/10.1094/mpmi-02-17-0036-r.

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Esca disease is one of the major grapevine trunk diseases in Europe and the etiology is complex, since several inhabiting fungi are identified to be associated with this disease. Among the foliar symptom expressions, the apoplectic form may be distinguished and characterized by sudden dieback of shoots, leaf drop, and shriveling of grape clusters in a few days that can ultimately induce the plant death. To further understand this drastic event, we conducted transcriptomic and metabolomic analyses to characterize responses of leaves during the period preceding symptom appearance (20 and 7 days before foliar symptom expression) and at the day of apoplexy expression. Transcriptomic and metabolomic analyses provide signatures for the apoplectic leaves and most changes concerning the metabolism of carbohydrates, amino acids, and phenylpropanoids. In deciphering glutathione-S-transferase (GST), its preferential location in phloem, correlated with the upregulation of GST genes and a decrease of the glutathione level, offers further support to the putative role of glutathione during apoplexy expression.
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DEL FRARI, Giovanni, Francesco CALZARANO et Ricardo BOAVIDA FERREIRA. « Understanding the control strategies effective against the esca leaf stripe symptom : the edge hypothesis ». Phytopathologia Mediterranea 61, no 1 (13 mai 2022) : 153–64. http://dx.doi.org/10.36253/phyto-13295.

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A peculiar symptom that may develop in grapevines affected by wood pathogens involved in the esca complex of diseases is the leaf stripe symptom, which also gives the name to the Grapevine Leaf Stripe Disease. Multiple studies have revealed strong links between fungal presence, wood symptomatology and expression of the leaf stripe symptom. However, numerous other factors have been shown to play roles in symptom onset, incidence, severity and yearly fluctuation of this disease. While the factors triggering the leaf stripe symptom are still under investigation, three control strategies have been proven effective for substantially reducing its expression, namely trunk surgery, and applications of sodium arsenite or a fertilizer mixture. These control strategies are examined here, including their (putative or confirmed) modes of action, and how they may influence the leaf stripe symptom development. In this article, we also propose the ‘edge’ hypothesis to tentatively explain symptoms onset, keeping in consideration past knowledge and recent advances in the understanding of the esca leaf stripe symptom. Ultimately, it is our intention to offer food-for-thought and stimulate debate within the phytopathological community.
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Mondello, Vincenzo, Aurélie Songy, Enrico Battiston, Catia Pinto, Cindy Coppin, Patricia Trotel-Aziz, Christophe Clément, Laura Mugnai et Florence Fontaine. « Grapevine Trunk Diseases : A Review of Fifteen Years of Trials for Their Control with Chemicals and Biocontrol Agents ». Plant Disease 102, no 7 (juillet 2018) : 1189–217. http://dx.doi.org/10.1094/pdis-08-17-1181-fe.

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Grapevine trunk diseases (GTDs) represent one of the most important problems for viticulture worldwide. Beyond the original causes of this outbreak in some countries like France, the lack of efficient control protocols and the prohibition of using active ingredients such as sodium arsenite and benzimidazoles, until recently used to reduce the impact of some GTDs but deleterious for humans and the environment, have probably worsened the impact of the diseases, leading to increasing economic losses. Since 1990, searches have been made to find efficient tools to control GTDs, testing a wide range of active ingredients and biocontrol agents. This review provides readers with an overview of the results reported in the scientific literature over the last 15 years. In particular, the review focuses on the trials carried out applying chemicals or microorganisms to control Esca complex diseases, Botryosphaeria dieback, and Eutypa dieback, the most widespread GTDs.
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Calvo-Garrido, Carlos, Aurélie Songy, Ariadna Marmol, Rafael Roda, Christophe Clément et Florence Fontaine. « Description of the relationship between trunk disease expression and meteorological conditions, irrigation and physiological response in Chardonnay grapevines ». OENO One 55, no 2 (20 avril 2021) : 97–113. http://dx.doi.org/10.20870/oeno-one.2021.55.2.4548.

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Esca disease and Botryosphaeria dieback are currently considered as serious grapevine diseases which affect vineyard health and induce economic losses. Both of these trunk diseases (GTDs) are caused by a complex of pathogens, and foliar expression is influenced by several factors, including environmental factors such as water stress. To manage water stress in some vine areas, culture practice based on irrigation systems for limiting water stress have been developed; however, little knowledge of the influence of such systems on GTD emergence is currently available. The present paper addresses the impact of irrigation systems and climatic factors (rainfall and temperature) on the expression of GTDs, specifically esca and Botryosphaeria dieback. A field experiment on Chardonnay in North East Spain, a vine growing area where drought is present and which is managed by an irrigation system, was therefore carried out during a 3-year period. The water stress impact on GTD expression was evaluated by measuring the GTD incidence and analysing different physiological parameters at different phenological stages, including principal component analysis and gene expression. The main finding of this study was the significant roles of vine transpiration and water availability, which depend on irrigation volume and rainfall amount; together, they may explain the erratic symptom expression in plants infected by GTD fungi depending on the year. All these parameters are discussed to better understand the relationship between GTD expression, irrigation system and climatic factors.
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Reveglia, Pierluigi, Regina Billones-Baaijens et Sandra Savocchia. « Phytotoxic Metabolites Produced by Fungi Involved in Grapevine Trunk Diseases : Progress, Challenges, and Opportunities ». Plants 11, no 23 (5 décembre 2022) : 3382. http://dx.doi.org/10.3390/plants11233382.

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Grapevine trunk diseases (GTDs), caused by fungal pathogens, are a serious threat to vineyards worldwide, causing significant yield and economic loss. To date, curative methods are not available for GTDs, and the relationship between the pathogen and symptom expression is poorly understood. Several plant pathologists, molecular biologists, and chemists have been investigating different aspects of the pathogenicity, biochemistry, and chemical ecology of the fungal species involved in GTDs. Many studies have been conducted to investigate virulence factors, including the chemical characterization of phytotoxic metabolites (PMs) that assist fungi in invading and colonizing crops such as grapevines. Moreover, multidisciplinary studies on their role in pathogenicity, symptom development, and plant-pathogen interactions have also been carried out. The aim of the present review is to provide an illustrative overview of the biological and chemical characterization of PMs produced by fungi involved in Eutypa dieback, Esca complex, and Botryosphaeria dieback. Moreover, multidisciplinary investigations on host-pathogen interactions, including those using cutting-edge Omics techniques, will also be reviewed and discussed. Finally, challenges and opportunities in the role of PMs for reliable field diagnosis and control of GTDs in vineyards will also be explored.
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TOMOIAGA, Liliana Lucia, et Veronica Sanda CHEDEA. « Grapevine Trunk Diseases Management in Vineyards from Central Transylvania ». Bulletin of University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca. Horticulture 77, no 1 (3 juin 2020) : 117. http://dx.doi.org/10.15835/buasvmcn-hort:2019.0041.

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Grapevine trunk diseases (GTD) are among the most important diseases reported in vineyards in central Transylvania. On average, up to 5% of the vineyards are affected by the GTD although there are also vineyards where the incidence of the attack exceeds 15%. Recent studies show that the importance of pathogens in wood is so great that they are considered limiting factors that affect the stability of the world’s vineyards. The main objective of this study is to develop new sustainable management alternatives for the GTD control. For this purpose, an agroecological variant including prophylactic and cultural measures and two treatments with biofungicides based on: Trichoderma atroviride strain 8, Trichoderma atroviride strain B11 and Trichoderma harzianum, were tested. The frequency of the attack of the main four GTD diseases (Esca complex, Phomopsis dieback, Eutypa dieback and Crown gall) on the SCDVV Blaj homologated grapevine varieties, ‘Astra’, ‘Amurg’, ‘Brumariu’, ‘Blasius’ ‘Radames’, ‘Rubin’ and ‘Selena’, was assessed showing that these had a lower frequency of the symptoms compared with the widely cultivated variety ‘Feteasca regala’. Also the effect of training system (Classical versus semi-high Guyot) on GTD is presented. The classical system had decreased the frequency of crown gall and Phomopsis dieback, and the semi-high Guyot system had decreased Eutypa dieback’s frequency, indicating that the training system is an important tool of the agroecological system in maintaing the health of grapevine. Biofungicides tested help reduce the symptoms of GTD, but not enough to help reduce the premature death of grapevine.
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Hillis, Vicken, Mark Lubell, Jonathan Kaplan et Kendra Baumgartner. « Preventative Disease Management and Grower Decision Making : A Case Study of California Wine-Grape Growers ». Phytopathology® 107, no 6 (juin 2017) : 704–10. http://dx.doi.org/10.1094/phyto-07-16-0274-r.

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Preventative disease management is challenging to farmers because it requires paying immediate costs in the hopes of returning uncertain future benefits. Understanding farmer decision making about prevention has the potential to reduce disease incidence and minimize the need for more costly postinfection practices. For example, the grapevine trunk-disease complex (esca, Botryosphaeria dieback, Eutypa dieback, and Phomopsis dieback) significantly affects vineyard productivity and longevity. Given the chronic nature of the infections and inability to eradicate the fungal pathogens, the preventative practices of delayed pruning, applications of pruning-wound protectants, and double pruning (also known as prepruning) are the most effective means of management. We surveyed wine-grape growers in six regions of California on their use of these three practices. In spite of acknowledging the yield impacts of trunk diseases, a substantial number of respondents either choose not to use preventative practices or incorrectly adopted them in mature vineyards, too late in the disease cycle to be effective. Growers with more negative perceptions of cost efficacy were less likely to adopt preventative practices or were more likely to time adoption incorrectly in mature vineyards. In general, preventative management may require strong intervention in the form of policy or extension to motivate behavioral change.
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Bhatt, Shantanu, Adrianne Nehrling Edwards, Hang Thi Thu Nguyen, Didier Merlin, Tony Romeo et Daniel Kalman. « The RNA Binding Protein CsrA Is a Pleiotropic Regulator of the Locus of Enterocyte Effacement Pathogenicity Island of Enteropathogenic Escherichia coli ». Infection and Immunity 77, no 9 (6 juillet 2009) : 3552–68. http://dx.doi.org/10.1128/iai.00418-09.

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ABSTRACT The attaching and effacing (A/E) pathogen enteropathogenic Escherichia coli (EPEC) forms characteristic actin-filled membranous protrusions upon infection of host cells termed pedestals. Here we examine the role of the RNA binding protein CsrA in the expression of virulence genes and proteins that are necessary for pedestal formation. The csrA mutant was defective in forming actin pedestals on epithelial cells and in disrupting transepithelial resistance across polarized epithelial cells. Consistent with reduced pedestal formation, secretion of the translocators EspA, EspB, and EspD and the effector Tir was substantially reduced in the csrA mutant. Purified CsrA specifically bound to the sepL espADB mRNA leader, and the corresponding transcript levels were reduced in the csrA mutant. In contrast, Tir synthesis was unaffected in the csrA mutant. Reduced secretion of Tir appeared to be in part due to decreased synthesis of EscD, an inner membrane architectural protein of the type III secretion system (TTSS) and EscF, a protein that forms the protruding needle complex of the TTSS. These effects were not mediated through the locus of enterocyte effacement (LEE) transcriptional regulator GrlA or Ler. In contrast to the csrA mutant, multicopy expression of csrA repressed transcription from LEE1, grlRA, LEE2, LEE5, escD, and LEE4, an effect mediated by GrlA and Ler. Consistent with its role in other organisms, CsrA also regulated flagellar motility and glycogen levels. Our findings suggest that CsrA governs virulence factor expression in an A/E pathogen by regulating mRNAs encoding translocators, effectors, or transcription factors.
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BRUNO, Giovanni Luigi, Maria Paola IPPOLITO, Francesco MANNERUCCI, Luca BRAGAZZI et Franca TOMMASI. « Physiological responses of ‘Italia’ grapevines infected with Esca pathogens ». Phytopathologia Mediterranea 60, no 2 (13 septembre 2021) : 321–36. http://dx.doi.org/10.36253/phyto-12171.

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Physiological features were examined of a 20-year-old Vitis vinifera ‘Italia’ table grape vineyard cropped in Apulia, Italy. Healthy vines with no foliar symptoms and any indications of wood or berry alterations, vines with natural wood infections by Phaeoacremonium minimum (syn. P. aleophilum) and Phaeomoniella chlamydospora showing brown wood streaking symptoms, and vines naturally infected with P. minimum, P. chlamydospora and Fomitiporia mediterranea with brown wood streaking and white rot symptoms, were surveyed. Bleeding xylem sap, collected at bud-break from healthy vines showed the greatest total ascorbic acid level, while vines with brown wood streaking and white rot had the greatest viscosity coefficient, glutathione concentration, and plant growth regulator activities. Compared to healthy vines, leaves of wood affected vines, sampled during the unfolded leaf, fruit setting, cluster closing and bunch ripening vine growth stages, had reduced fresh and dry weights, total chlorophyll concentrations, and increased leaf surface area. Low ascorbic acid and reduced glutathione concentrations, weak redox state, and moderate levels of dehydroascorbic acid and oxidized glutathione were also detected in these vines. Analyses also detected reduced activities of dehydroascorbate reductase, ascorbate free radical reductase and glutathione reductase in diseased vines. The cell membrane damage, associated with lipid peroxidation, was coupled with high hydrogen peroxide concentrations. These changes could contribute to the cell death of leaves and foliar symptom development. The ascorbate-glutathione cycle supports grapevine susceptibility to Esca complex-associated fungi.
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Fu, Li, Yan-Ru Qin, Xiao-Yan Ming, Xian-Bo Zuo, Yu-Wen Diao, Li-Yi Zhang, Jiaoyu Ai et al. « RNA editing of SLC22A3 drives early tumor invasion and metastasis in familial esophageal cancer ». Proceedings of the National Academy of Sciences 114, no 23 (22 mai 2017) : E4631—E4640. http://dx.doi.org/10.1073/pnas.1703178114.

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Like many complex human diseases, esophageal squamous cell carcinoma (ESCC) is known to cluster in families. Familial ESCC cases often show early onset and worse prognosis than the sporadic cases. However, the molecular genetic basis underlying the development of familial ESCC is mostly unknown. We reported that SLC22A3 is significantly down-regulated in nontumor esophageal tissues from patients with familial ESCC compared with tissues from patients with sporadic ESCCs. A-to-I RNA editing of the SLC22A3 gene results in its reduced expression in the nontumor esophageal tissues of familial ESCCs and is significantly correlated with lymph node metastasis. The RNA-editing enzyme ADAR2, a familial ESCC susceptibility gene identified by our post hoc genome-wide association study, is positively correlated with the editing level of SLC22A3. Moreover, functional studies showed that SLC22A3 is a metastasis suppressor in ESCC, and deregulation of SLC22A3 facilitates cell invasion and filopodia formation by reducing its direct association with α-actinin-4 (ACTN4), leading to the increased actin-binding activity of ACTN4 in normal esophageal cells. Collectively, we now show that A-to-I RNA editing of SLC22A3 contributes to the early development and progression of familial esophageal cancer in high-risk individuals.
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Telesh, A., et T. Morozova. « THE POSSIBILITIES OF COMPLEX VISUAL DIAGNOSTICS OF LIVER PATHOLOGY IN PATIENTS WITH DIFFUSE LIVER DISEASES ASSOCIATED WITH COVID-19. » East European Scientific Journal 4, no 11(75) (16 décembre 2021) : 41–45. http://dx.doi.org/10.31618/essa.2782-1994.2021.4.75.173.

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The research shows the possibilities of visual diagnostics of liver pathology in patients with various diffuse liver diseases and COVID-19. The analysis is based on the results of examination of patients, who got hospital treatment in Clinical Hospital №1 of Smolensk from September to November 2021. The research shows the efficiency of ultrasound diagnosis as the first step of examination. Using Magnetic Resonance Imaging (MRI) allowed to study the symptoms of liver pathology more deeply. In order to improve the exact specific diagnosis of liver pathology in patients with diffuse liver diseases and COVID-19, arterial spin labeling technique is recommended to use. The research shows the efficiency of complex using of diagnostic methods in patients with diffuse liver diseases and SARS-CoV-2 infection
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Wang, Zhiwei, Ling Ran, Chunxia Chen, Ranran Shi, Yu Dong, Yubing Li, Xiuman Zhou et al. « Identification of HLA-A2-Restricted Mutant Epitopes from Neoantigens of Esophageal Squamous Cell Carcinoma ». Vaccines 9, no 10 (1 octobre 2021) : 1118. http://dx.doi.org/10.3390/vaccines9101118.

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Esophageal squamous cell carcinoma (ESCC), one of the deadliest gastrointestinal cancers, has had limited effective therapeutic strategies up to now. Accumulating evidence suggests that effective immunotherapy in cancer patients has been associated with T cells responsive to mutant peptides derived from neoantigens. Here, we selected 35 human leukocyte antigen-A2 (HLA-A2)-restricted mutant (MUT) peptides stemmed from neoantigens of ESCC. Among them, seven mutant peptides had potent binding affinity to HLA-A*0201 molecules and could form a stable peptide/HLA-A*0201 complex. Three mutant peptides (TP53-R267P, NFE2L2-D13N, and PCLO-E4090Q) of those were immunogenic and could induce the cytotoxic T lymphocytes (CTLs) recognizing mutant peptides presented on transfected cells in an HLA-A2-restricted and MUT peptide-specific manner. In addition, the CTL response in immunized HLA-A2.1/Kb transgenic (Tg) mice was enhanced by coupling MUT peptides to peptide WH, a peptide delivery carrier targeting Clec9a+ DCs. Then, the possible binding model conversions between the WT and MUT candidate peptides were analyzed by docking with the pockets of HLA-A*0201 molecule. We therefore propose a novel strategy and epitopes for immunotherapy of ESCC based on neoantigens.
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Dossou, Mahulome Anne-Marie. « Drainage of purulent wounds of soft tissues (review article) ». Tambov Medical Journal, no 4 (2022) : 47–52. http://dx.doi.org/10.20310/2782-5019-2022-4-4-47-52.

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Abstract. Wound infection and purulent-inflammatory diseases of soft tissues in surgery are an urgent problem that requires an integrated approach to treatment. One of the key factors to eliminate this pathology is drainage. The purpose of this review is to study the principles and methods of drainage used, in particular those used in the treatment of purulent soft tissue wounds. To study this issue, we analyzed the educational and applied literature, scientific literature from List of HAC, databases SCOPUS, RSCI, ESCI, CAS, PUBMED. We note the results of applying various drainage methods. A surgical operation does not always lead to the complete elimination of the inflammatory process, which can be aggravated by the appearance of exudation, natural necrosis, and the development of pathogenic microflora. To ensure in the postoperative period a complex cleansing of the wound from exudate, necrosis products, microbial flora, different drainage methods are used. After studying the current literature, one can not only be convinced of the need for drainage, but also clearly trace the development of drainage principles that are aimed at combining physical and pharmacological methods of wound cleaning with the maximum possible elimination of the negative iatrogenic factor.
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Mack, Andrew R., Christopher Bethel, Magdalena A. Taracilla, Focco van den Akker, Brittany A. Miller, Tsuyoshi Uehara, David A. Six, Krisztina M. Papp-Wallace et Robert A. Bonomo. « 1286. Taniborbactam Inhibits Cefepime-Hydrolyzing Variants of Pseudomonas-derived Cephalosporinase (PDC) ». Open Forum Infectious Diseases 8, Supplement_1 (1 novembre 2021) : S731—S732. http://dx.doi.org/10.1093/ofid/ofab466.1478.

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Abstract Background PDC is a class C β-lactamase in P. aeruginosa. PDC-88 is a variant characterized by a Thr-Pro amino acid deletion in the R2-loop (Δ289-290; Fig. 1). This deletion reduces susceptibility to cefepime (FEP), ceftazidime (CAZ), and ceftolozane-tazobactam (TOL/TZB), but the mechanism for this “gain of function” is unknown. Taniborbactam (TAN) is a novel cyclic boronate β-lactamase inhibitor (BLI) with activity against all four β-lactamase classes and is currently undergoing a phase 3 clinical trial paired with FEP. Herein, we studied the extended-spectrum AmpC (ESAC) phenotype of PDC-88 and examined the ability of TAN to inhibit this variant. Structure of PDC-1 (PDB ID: 4GZB) with PDC-88 deleted residues in red and substitutions in green. All four amino acid substitutions (T79A, V178L, V329I, and G346A) are common (occurring in 10% or more of PDC variants) and have not been associated with resistance. Image rendered using UCSF Chimera. Methods Broth microdilution minimum inhibitory concentrations (MIC) were determined in accordance with CLSI. PDC-3 and PDC-88 were purified, and steady-state enzyme kinetics were determined. Quadrupole time-of-flight mass spectrometry (Q-TOF-MS) was performed. Results In isogenic E. coli expressing PDC-3 or PDC-88, FEP MIC increased 8- or 128-fold, respectively, compared to the empty vector. Addition of TAN at 4 μg/ml restored FEP activity with MIC lowered to 0.25 μg/ml (Table 1) for both PDC-3 and PDC-88 bearing strains. PDC-88 demonstrated a 9-fold lower KM, 3.4-fold lower kcat, and 2.6-fold higher kcat/KM for FEP compared to PDC-3 (Table 2A). TAN Ki values were 4- to 10-fold lower than avibactam (AVI) and 40- to 95-fold lower than TZB. The TAN acylation constant (k2/K) was 7- to 12-fold greater than AVI and 133- to 366-fold higher than TZB (Table 2B). Q-TOF-MS revealed faster deacylation of FEP by PDC-88 compared to TOL and CAZ. TOL was acylated and deacylated by PDC-88 but not by PDC-3. CAZ was readily acylated but slowly deacylated by PDC-88 compared to PDC-3 (Fig. 2). Cefepime Minimum Inhibitory Concentration (MIC) for PDC-1 and a series of partial R2-loop deletions with and without taniborbactam, avibactam, and tazobactam. In all variants, taniborbactam and avibactam restored susceptiblity while tazobactam is less effective against PDC-88 and variants. Summary of kinetic constants. (A) Comparison of Michaelis constant (KM), turnover number (kcat), and catalytic efficiency (kcat/KM) of nitrocefin and cefepime with PDC-3 and PDC-88. (B) Comparison of inhibition constant (Ki) and acylation constant (k2/K) for avibactam, tazobactam, and taniborbactam with PDC-3 and PDC-88. Graphical summary of mass spectrometry results for substrate acyl-enzyme complex capture experiments. FEP, cefepime; CAZ, ceftazidime; TOL, ceftolozane. Primes indicate a modified substrate (loss of R2 group). TOL does not form an acyl-enzyme complex with PDC-3. Conclusion Different kinetic constants are responsible for the elevated cephalosporin MICs. We posit that PDC-88 increases FEP MIC by enhanced hydrolysis; TOL MICs by enabling acylation; and CAZ MICs by both trapping and enhanced hydrolysis. TAN inhibits both PDC-3 and PDC-88 with similar kinetic profiles. Notably, TAN appears to be a more efficient inhibitor of PDC than current BLIs targeted for use against P. aeruginosa (lower Ki, higher k2/K values). The combination of TAN and FEP may represent an important treatment option for P. aeruginosa isolates that develop ESAC phenotypes. Disclosures Focco van den Akker, PhD, Venatorx Pharmaceuticals, Inc. (Grant/Research Support) Brittany A. Miller, BS, Venatorx Pharmaceuticals, Inc. (Employee) Tsuyoshi Uehara, PhD, Venatorx Pharmaceuticals, Inc. (Employee) David A. Six, PhD, Venatorx Pharmaceuticals, Inc. (Employee) Krisztina M. Papp-Wallace, Ph.D., Merck & Co., Inc. (Grant/Research Support)Spero Therapeutics, Inc. (Grant/Research Support)Venatorx Pharmaceuticals, Inc. (Grant/Research Support)Wockhardt Ltd. (Other Financial or Material Support, Research Collaborator) Robert A. Bonomo, MD, entasis (Research Grant or Support)Merck (Grant/Research Support)NIH (Grant/Research Support)VA Merit Award (Grant/Research Support)VenatoRx (Grant/Research Support)
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Soloviova, Alina, Olha Kaliuzhnaia, Oksana Strilets, Dmytro Lytkin et Olga Goryacha. « The main stages of pharmaceutical development of emulgel “Probioskin” ». ScienceRise : Pharmaceutical Science, no 6 (34) (30 décembre 2021) : 75–84. http://dx.doi.org/10.15587/2519-4852.2021.249710.

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The aim. To conduct research on the pharmaceutical development of a complex preparation with probiotic “Probioskin” in the form of an emulgel for the treatment of infectious and inflammatory dermatological diseases. Methods. Uniformity was determined by visual inspection of the test samples using an XSP-128 ULAB biological microscope. The study of the rheological properties of the samples was carried out using a Rheolab QC rheovisosimeter (Anton Paar, Austria) using a system of coaxial cylinders C-CC27 / SS. Microbiological studies and biotesting on a biological model of ciliates were carried out in aseptic conditions of a laminar box (biological safety cabinet AC2-4E1 “Esco”, Indonesia) of the Department of Biotechnology of the National University of Pharmacy (completely). Pharmacological studies (determination of the parameters of acute toxicity and anti-inflammatory properties on the model of acute exudative inflammation of the foot in rats caused by zymosan and carrageenan) were carried out on the basis of the Central Research Laboratory of the NUPh. Results. On the basis of the complex of the carried out studies, the composition of the complex preparation for skin use “Probioskin” was substantiated. The analysis of the microbiological purity of the developed agent during the proposed shelf life of 12 months showed that the drug meets the requirements of the State Pharmacopoeia Monograph for cutaneous application in terms of the level of microbial contamination by foreign microflora. The complex of pharmacological studies carried out indicates that the drug “Probioskin” can be attributed to group 6 of class and classified as a “relatively harmless” agent. The study of the anti-inflammatory effect of the drug indicates that the drug exhibits moderate anti-inflammatory properties. Under the condition of zymosan inflammation, which is associated with the activation of leukotrienes as inflammatory mediators, the average antiexudative activity of the drug is 33 %. The drug has a moderate antiexudative effect under the condition of carrageenan edema, which is evidence of its effect on exudation processes mediated by prostaglandins. The mean AEA of the study drug was 24 %. Conclusions. For the development of a soft preparation for skin use for the treatment of infectious and inflammatory dermatological diseases, the following components have been selected: active – lactobacilli, dexpanthenol, lactic acid; auxiliary - propylene glycol, peach oil, polysorbate-80, aristophlex, tocopherol, the concentration of which was substantiated on the basis of a complex of organoleptic, physicochemical, pharmacological, microbiological and biological studies. It has been experimentally established that the “Probioskin” emulgel meets the requirements of the SPhU in terms of the level of microbial contamination by extraneous microflora. Pharmacological studies allow the drug to be classified as “relatively harmless” with anti-inflammatory properties at a level not lower than the reference drug
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Pires, João, Magdalena Taracila, Christopher R. Bethel, Yohei Doi, Sara Kasraian, Regula Tinguely, Parham Sendi, Robert A. Bonomo et Andrea Endimiani. « In VivoEvolution of CMY-2 to CMY-33 β-Lactamase in Escherichia coli Sequence Type 131 : Characterization of an Acquired Extended-Spectrum AmpC Conferring Resistance to Cefepime ». Antimicrobial Agents and Chemotherapy 59, no 12 (21 septembre 2015) : 7483–88. http://dx.doi.org/10.1128/aac.01804-15.

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ABSTRACTCefepime is frequently prescribed to treat infections caused by AmpC-producing Gram-negative bacteria. CMY-2 is the most common plasmid-mediated AmpC (pAmpC) β-lactamase. Unfortunately, CMY variants conferring enhanced cefepime resistance have been reported. Here, we describe the evolution of CMY-2 to an extended-spectrum AmpC (ESAC) in clonally identicalEscherichia coliisolates obtained from a patient. The CMY-2-producingE. coliisolate (CMY-2-Ec) was isolated from a wound. Thirty days later, one CMY-33-producingE. coliisolate (CMY-33-Ec) was detected in a bronchoalveolar lavage fluid sample. Two weeks before the isolation of CMY-33-Ec, the patient received cefepime. CMY-33-Ecand CMY-2-Ecwere identical by repetitive extragenic palindromic-PCR (rep-PCR), being of hyperepidemic sequence type 131 (ST131) but showing different β-lactam MICs (e.g., cefepime MIC, 16 and ≤0.5 μg/ml for CMY-33-Ecand CMY-2-Ec, respectively). Identical CMY-2-Ecisolates were also found in a rectal swab. CMY-33 differs from CMY-2 by a Leu293-Ala294 deletion. Expressed inE. colistrain DH10B, both CMYs conferred resistance to ceftazidime (≥256 μg/ml), but the cefepime MICs were higher for CMY-33 than CMY-2 (8 versus 0.25 μg/ml, respectively). Thekcat/Kmor inhibitor complex inactivation (kinact)/Kiapp(μM−1s−1) indicated that CMY-33 possesses an extended-spectrum β-lactamase (ESBL)-like spectrum compared to that of CMY-2 (e.g., cefoxitin, 0.2 versus 0.4; ceftazidime, 0.2 versus not measurable; cefepime, 0.2 versus not measurable; and tazobactam, 0.0018 versus 0.0009, respectively). Using molecular modeling, we show that a widened active site (∼4-Å shift) may play a significant role in enhancing cefepime hydrolysis. This is the firstin vivodemonstration of a pAmpC that under cephalosporin treatment expands its substrate spectrum, resembling an ESBL. The prevalence of CMY-2-Ecisolates is rapidly increasing worldwide; therefore, awareness that cefepime treatment may select for resistant isolates is critical.
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Ye, Qingtong, Jingyi Jia, Ishara S. Manawasinghe, Xinghong Li, Wei Zhang, Laura Mugnai, Xuehong Wu, Kevin D. Hyde et Jiye Yan. « Fomitiporia punicata and Phaeoacremonium minimum associated with Esca complex of grapevine in China ». Phytopathology Research 3, no 1 (25 mai 2021). http://dx.doi.org/10.1186/s42483-021-00087-w.

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AbstractThe Esca disease complex includes some of the most important trunk diseases of grapevines (Vitis spp.) and causes serious yield losses in grape production worldwide. However, there has been no detailed study on its presence and associated pathogens in China. During 2017–2019, a preliminary field survey was conducted in eight vineyards in Hebei and Ningxia provinces, China when unusual foliar symptoms were observed. Symptoms were distinct tiger striped leaves, which are typical of grapevine leaf stripe disease (GLSD), one of the most common diseases in the Esca complex. Tiger-stripe leaf symptoms were found in four vineyards, and incidence was cultivar dependent varying with vineyard and year. A total of 266 fungal isolates were obtained from wood tissues of grapevines with typical foliar symptoms of GLSD. Based on morphological characters and multigene-combined phylogenetic analyses, the Ascomycete Phaeoacremonium minimum, one of the pathogens associated with Esca complex was identified. The basidiomycete Fomitiporia punicata, which has never been reported infecting grapevine, was also identified and found to be associated with wood rot in grapevine. The remaining isolates included some known wood pathogens, such as Neofusicoccum species and Diaporthe species. Koch’s postulates were performed in the greenhouse, confirming that both F. punicata and P. minimum caused leaf interveinal chlorosis and necrosis that resembled the GLSD symptoms of the Esca complex observed in the field. The present study provides the first detailed report of the Esca complex in China. In addition, this is the first record of F. punicata associated with Esca complex of grapevine worldwide. The results of this study provide new insights into the knowledge of the Esca complex.
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Kovács, Cs, et E. Sándor. « The increasing importance of grapevine trunk diseases ». International Journal of Horticultural Science 22, no 3-4 (18 octobre 2016). http://dx.doi.org/10.31421/ijhs/22/3-4./1188.

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Grapevine trunk diseases (GTDs) are destroying the woody parts of the plants, resulting decline or dieback of the grapevine. More detailed research of the GTD began in 1950s, when Hewitt et al. (1957) observed that specific symptoms cannot be detected on the diseased trunks every year. Latest results have also proved that abiotic factors affect the appearance and the severity of the disease. Moreover several pathogenic fungi may play role as causative agents (Bertsch et al., 2013). Eutypa, Botryosphaeria, Phomopsis dieback, esca disease complex, and Petri disease are considered the major GTDs, where a variety of pathogens attack the woody perennial organs of the vine and ultimately lead to the death of the plant (Lehoczky, 1974; Larignon & Dubos, 1997; Rolshausen et al. 2010; Kotze et al., 2011; Bertsch et al., 2013; Fontaine et al., 2015).The GTD incidence has been reported to be increased during the last decades (Úrbez-Torres et al., 2014). The esca incidence has reached 60% to 80% in some old vineyards in southern Italy (Pollastro et al., 2000; Surico et al., 2000; Calzarano & Di Marco, 2007). The disease incidence of the esca was reported to be increased from 1.83% to almost 13%, between 2003 and 2007 in Hungary (Dula, 2011). There was detected a five times increase in the GTD disease incidence in the Tokaj Wine Region, Hungary between 2014 and 2016 (Bihari et al,2016).
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Chervin, Justine, Ana Romeo-Oliván, Sylvie Fournier, Virginie Puech-Pages, Bernard Dumas, Alban Jacques et Guillaume Marti. « Modification of Early Response of Vitis vinifera to Pathogens Relating to Esca Disease and Biocontrol Agent Vintec® Revealed By Untargeted Metabolomics on Woody Tissues ». Frontiers in Microbiology 13 (2 mars 2022). http://dx.doi.org/10.3389/fmicb.2022.835463.

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Esca disease is one of the most destructive grapevine trunk diseases. Phaeoacremonium minimum and Phaeomoniella chlamydospora are two of the known fungal pathogens associated with this disease. Today, biocontrol agents against Esca are mainly based on the use of the strain of the mycoparasite fungal genus Trichoderma such as the Vintec® product. The aim of this study was to investigate early response of woody tissues to Esca pathogens and identify metabolites that could be correlated with a biocontrol activity within a complex woody matrix. An untargeted liquid chromatography–high-resolution mass spectrometry metabolomic approach coupled to a spectral similarity network was used to highlight clusters of compounds associated with the plant response to pathogens and biocontrol. Dereplication highlighted the possible role of glycerophospholipids and polyphenol compounds, the latest mainly belonging to stilbenoids. Antifungal activity of some relevant biomarkers, evaluated in vitro on Phaeomoniella chlamydospora and Botrytis cinerea, suggests that some of these compounds can play a role to limit the development of Esca pathogens in planta.
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Qin, Guimin, Luqiong Yang, Yuying Ma, Jiayan Liu et Qiuyan Huo. « The exploration of disease-specific gene regulatory networks in esophageal carcinoma and stomach adenocarcinoma ». BMC Bioinformatics 20, S22 (décembre 2019). http://dx.doi.org/10.1186/s12859-019-3230-6.

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Abstract Background Feed-forward loops (FFLs), consisting of miRNAs, transcription factors (TFs) and their common target genes, have been validated to be important for the initialization and development of complex diseases, including cancer. Esophageal Carcinoma (ESCA) and Stomach Adenocarcinoma (STAD) are two types of malignant tumors in the digestive tract. Understanding common and distinct molecular mechanisms of ESCA and STAD is extremely crucial. Results In this paper, we presented a computational framework to explore common and distinct FFLs, and molecular biomarkers for ESCA and STAD. We identified FFLs by combining regulation pairs and RNA-seq data. Then we constructed disease-specific co-expression networks based on the FFLs identified. We also used random walk with restart (RWR) on disease-specific co-expression networks to prioritize candidate molecules. We identified 148 and 242 FFLs for these two types of cancer, respectively. And we found that one TF, E2F3 was related to ESCA, two genes, DTNA and KCNMA1 were related to STAD, while one TF ESR1 and one gene KIT were associated with both of the two types of cancer. Conclusions This proposed computational framework predicted disease-related biomolecules effectively and discovered the correlation between two types of cancers, which helped develop the diagnostic and therapeutic strategies of Esophageal Carcinoma and Stomach Adenocarcinoma.
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Di Marco, Stefano, Elisa Giorgia Metruccio, Samuele Moretti, Marco Nocentini, Giuseppe Carella, Andrea Pacetti, Enrico Battiston, Fabio Osti et Laura Mugnai. « Activity of Trichoderma asperellum Strain ICC 012 and Trichoderma gamsii Strain ICC 080 Toward Diseases of Esca Complex and Associated Pathogens ». Frontiers in Microbiology 12 (28 janvier 2022). http://dx.doi.org/10.3389/fmicb.2021.813410.

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Grapevine trunk diseases are widespread in all grape-growing countries. The diseases included in the Esca complex of diseases are particularly common in European vineyards. Their distinctive foliar symptoms are well known to be associated not only with losses in quantity, as with all grapevine wood diseases, but also with losses in the quality of the crop. Protection of pruning wounds is known to reduce infections in artificial inoculations and, to some extent, reduce the external leaf symptoms. The application of biological control agents in the field is typically started at the first appearance of symptoms. In this article, the two strains belonging to two different species, Trichoderma asperellum ICC 012 and T. gamsii ICC 080, which are present in a commercial formulation, were tested in vitro, in vivo in artificial inoculation, and in the field in long-term experiments where the wounds on four young asymptomatic vineyards were protected since 1 or 2 years after planting. The in vitro trials highlighted the different temperature requirements of the two strains, the direct mycoparasitizing activity of T. asperellum, and the indirect activity shown by both Trichoderma strains. The in vivo trials confirmed the ability of the two strains to reduce the colonization following artificial inoculations with the high, unnatural concentration of spores used in artificial infections, even if with variable efficacy, and with long persistence as they could be reisolated 7 months post-application. The preventive applications carried out over 9 years showed a very high reduction in symptom development in the treated vines, on annual and cumulated incidence and on the death of vines, with disease reduction varying from 66 to almost 90%. Early and annual application of protection to the pruning wounds appears to be the best method for reducing damages caused by grapevine leaf stripe disease (a disease of the Esca complex of diseases). Trichoderma appears to offer an efficient, environmentally friendly, and long-lasting protection in the presence of a natural inoculum concentration.
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Perez-Gonzalez, Gabriel, Dana Sebestyen, Elsa Petit, Jody Jellison, Laura Mugnai, Eric Gelhaye, Norman Lee, Sibylle Farine, Christophe Bertsch et Barry Goodell. « Oxygen Radical-Generating Metabolites Secreted by Eutypa and Esca Fungal Consortia : Understanding the Mechanisms Behind Grapevine Wood Deterioration and Pathogenesis ». Frontiers in Plant Science 13 (4 juillet 2022). http://dx.doi.org/10.3389/fpls.2022.921961.

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Eutypa dieback and Esca complex are fungal diseases of grape that cause large economic losses in vineyards. These diseases require, or are enhanced by, fungal consortia growth which leads to the deterioration of the wood tissue in the grapevine trunk; however, pathogenesis and the underlying mechanisms involved in the woody tissue degradation are not understood. We examined the role that the consortia fungal metabolome may play the role in generating oxygen radicals that could potentially play a role in trunk decay and pathogenesis. Unique metabolites were isolated from the consortia fungi with some metabolites preferentially reducing iron whereas others were involved in redox cycling to generate hydrogen peroxide. Metabolite suites with different functions were produced when fungi were grown separately vs. when grown in consortia. Chelator-mediated Fenton (CMF) chemistry promoted by metabolites from these fungi allowed for the generation of highly reactive hydroxyl radicals. We hypothesize that this mechanism may be involved in pathogenicity in grapevine tissue as a causal mechanism associated with trunk wood deterioration/necrosis in these two diseases of grape.
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Ji, Tao, Valeria Altieri, Irene Salotti et Vittorio Rossi. « Effects of Temperature and Moisture Duration on Spore Germination of Four Fungi that Cause Grapevine Trunk Diseases ». Plant Disease, 18 octobre 2022. http://dx.doi.org/10.1094/pdis-08-22-1802-sc.

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Grapevine trunk diseases (GTDs) are serious threats worldwide and are difficult to control, in part because the environmental requirements for epidemiological processes of the causal fungi are poorly understood. We therefore investigated the effects of temperature and moisture duration on spore germination of four fungi associated with two GTDs (Esca complex and Eutypa dieback): Phaeomoniella chlamydospora (Pch), Phaeoacremonium minimum (Pm), Cadophora luteo-olivacea (Cl), and Eutypa lata (El). Conidia of Pch, Pm, and Cl were similar: conidia of these fungi germinated profusely (>90%) between 20 and 30°C; Pch and Pm tended to germinate at higher temperatures (up to 40°C for Pm), and Cl at lower temperatures (as low as 5°C). El ascospores germinated between 10 and 30°C. The required duration of moist periods for germination was shortest for Cl (about 6 h), followed by Pm and El (about 12 h), and Pch (about 24 h). Further research on the environmental requirements of GTD fungi may increase our ability to predict infection periods and to thereby improve disease control.
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Ji, Tao, Irene Salotti, Valeria Altieri, Ming Li et Vittorio Rossi. « Temperature-dependent growth and spore germination of fungi causing Grapevine Trunk Diseases : quantitative analysis of literature data ». Plant Disease, 10 novembre 2022. http://dx.doi.org/10.1094/pdis-09-22-2249-re.

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Grapevine trunk diseases (GTDs) are serious threats in all viticultural areas of the world, and their management is always complex and usually inadequate. Fragmented and inconsistent information on the epidemiology and environmental requirements of the causal fungi is among the reasons for poor disease control. We therefore conducted a quantitative analysis of literature data to determine the effects of temperature on mycelial growth and the effects of temperature and moisture duration on spore germination. Using the collected information, we then developed mathematical equations describing the response of mycelial growth to temperature, and the response of spore germination to temperature and moisture for the different species and disease syndromes. We considered 27 papers (selected from a total of 207 papers found through a systematic literature search) and 116 cases; these involved 43 fungal species belonging to three disease syndromes. The mycelial growth of the fungi causing Botryosphaeria dieback (BD) and the Esca complex (EC) responded similarly to temperature, and preferred higher temperatures than those causing Eutypa dieback (ED) (with optimal temperature of 25.3, 26.5°C, and 23.3°C, respectively). At any temperature, the minimal duration of the moist period required for 50% spore germination was shorter for BD (3.0 h) than for EC (17.2 h) or ED (15.5 h). Mathematical equations were developed accounting for temperature/moisture relationships of GTD fungi, which showed concordance correlation coefficients  0.888; such equations should be useful for reducing the risk of infection.
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Rosace, Maria Chiara, Sara Elisabetta Legler, Irene Salotti et Vittorio Rossi. « Susceptibility of pruning wounds to grapevine trunk diseases : A quantitative analysis of literature data ». Frontiers in Plant Science 14 (23 février 2023). http://dx.doi.org/10.3389/fpls.2023.1063932.

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IntroductionPruning wounds are the main entry points for fungi causing grapevine trunk diseases (GTDs). Several studies identified factors influencing the temporal dynamics of wound susceptibility, which include the fungal species and inoculum dose, weather conditions, grape variety, pruning date, and so forth. Here, we conducted a quantitative analysis of literature data to synthesise outcomes across studies and to identify the factors that most affect the length of pruning wound susceptibility.MethodsWe extracted data on the frequency at which the inoculated wounds showed GTD symptoms or an inoculated pathogen was reisolated following artificial inoculation at the time of pruning or in the following days. A negative exponential model was fit to these data to describe changes in wound susceptibility as a function of time since pruning, in which the rate parameter changed depending on specific factors.Results and DiscussionThe results show that wound susceptibility is high at the time of pruning, and they remain susceptible to invasion by GTD fungi for months after pruning. Infection incidence on wounds was higher for fungi associated with Botryosphaeria dieback than those associated with Eutypa dieback or Esca complex, and wound susceptibility decreased faster for Eutypa dieback than for other GTD agents. Grapevine variety and pruning season also affected the wound susceptibility period. Sauvignon Blanc remains susceptible to GTDs longer than other varieties. We also found that the time of pruning can affect infection dynamics, especially for more susceptible varieties. The results increase our understanding of GTD epidemiology and should help growers control infections.
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Pacetti, Andrea, Samuele Moretti, Célia Perrin, Eric Gelhaye, Evi Bieler, Hanns-Heinz Kassemeyer, Laura Mugnai, Sibylle Farine et Christophe Bertsch. « Grapevine Wood-Degrading Activity of Fomitiporia mediterranea M. Fisch. : A Focus on the Enzymatic Pathway Regulation ». Frontiers in Microbiology 13 (18 mars 2022). http://dx.doi.org/10.3389/fmicb.2022.844264.

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Fomitiporia mediterranea is a Basidiomycetes fungus associated with some of the Esca complex diseases and responsible for decay in grapevine wood. Its role in the onset of foliar symptoms has recently been reconsidered, mainly after evidence showing a reduction in foliar symptom expression after removal of rotten wood. The study of its degradation pathways has already been approached by other authors, and with this study much information is consolidated. A microscopic observation of degraded wood provides a first approach to the characterization of F. mediterranea modalities of wood cellular structure degradation. The decay of grapevine wood was reproduced in vitro, and the measurement of each wood-forming polymer loss highlighted characteristics of F. mediterranea common to selective white rot and showed how fungal strain and vine variety are factors determining the wood degradation. All these observations were supported by the analysis of the laccase and manganese peroxidase enzyme activity, as well as by the expression of the genes coding 6 putative laccase isoforms and 3 manganese peroxidase isoforms, thereby highlighting substantial intraspecific variability.
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Hernandez, Monica, et Achala KC. « A systematic survey on prevalence of grapevine trunk disease pathogens in Oregon vineyards ». Plant Disease, 11 septembre 2022. http://dx.doi.org/10.1094/pdis-05-22-1220-re.

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Grapevine trunk diseases (GTDs) are found in vineyards worldwide and can be caused by different fungal pathogens. To characterize types of GTDs in Oregon vineyards, and how the GTD pathogens’ prevalence is affected by two geographical regions, a survey was conducted in which grapevine trunk samples were collected from 15 and 14 wine grape (Vitis vinifera) vineyards in southern and northern Oregon respectively. Fungal species were identified through culture and PCR based methods. GTD pathogens that were identified included Botryosphaeriaceae spp. and Phaeoacremonium spp. from 72 and 21% of the surveyed vineyards respectively; Phaeomoniella chlamydospora, Cryptovalsa ampelina, Truncatella angustata, Seimatosporium lichenicola, Hormonema viticola from 7% of the surveyed vineyards; and Dactylonectria macrodidyma, and Pestaloptiopsis sp. from 3% of the surveyed vineyards. Pathogens were identified in both regions and in young and mature vineyards. The presence of GTD from the Botryosphaeria dieback complex was significantly affected by regions (P=0.021) with pathogens being significantly more abundant in Willamette Valley (northern region) compared to Rogue Valley (southern region) vineyards. Some differences among other tested variables such as vineyard age, cultivars, rootstocks, and pruning methods were observed for all disease complexes; however the differences were not statistically significant. Our study summarizes that Botryosphaeria dieback and Esca disease complexes are the most prevalent diseases infecting grapevines in Oregon vineyards and management practices need to be geared towards these economically important diseases. In addition, pathogens from other disease complexes are also present suggesting a need for regular disease monitoring and following practices to limit the spread of these pathogens.
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Battiston, Enrico, Sara Falsini, Alessio Giovannelli, Silvia Schiff, Corrado Tani, Roberta Panaiia, Alessio Papini, Stefano Di Marco et Laura Mugnai. « Xylem anatomy and hydraulic traits in Vitis grafted cuttings in view of their impact on the young grapevine decline ». Frontiers in Plant Science 13 (5 octobre 2022). http://dx.doi.org/10.3389/fpls.2022.1006835.

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Grapevine grafting is an essential practice in viticulture and over the years, various bench grafting techniques have been developed to mechanize the nursery process and to increase the yield in number of viable cuttings. Bench grafting is a fundamental nursery practice that can potentially affect the quality of propagation material also in young decline associated to grapevine trunk diseases and has been recently reported to influence leaf symptoms development associated with diseases of Esca complex. The study aimed to investigate how three bench grafting methods [i.e., (i) Omega graft as mechanical technique, (ii) Whip and Tongue graft as manual technique and (iii) Full Cleft graft as semi-mechanical technique] can influence these phenomena. Specifically, the different methods were compared for their effect on the anatomical development of the grafting point and the functionality of the xylem, also considering two factors: the grapevine cultivar (Cabernet Sauvignon, Glera and Teroldego) and the scion/rootstock diameter (thin and large). Observations by light microscopy on the anatomical evolution and measurements on the xylem morphology and hydraulic traits were correlated with the grafting methods and the investigated varieties. The anatomical observations revealed that the mechanical (Omega) and semi-mechanical (Full Cleft) grafting methods have a faster callusing response while the manual technique (Whip and Tongue) has a slower but greater vascularization of the differentiated callus. Significant differences between cultivars and/or grafting types were also detected in necrotic area on the grafted tissues. Statistical analysis of the grapevine vessels suggested differences in xylem parameters between cultivars, while grafting type had no significant effects. On the other hand, the grafting type significantly affected the intrinsic growth rate. The study confirms the potential incidence of lesions and dysfunctionalities correlated with the grafting method applied, which can potentially induce grafted vine declines in vineyards due to the necrotic area detected on the grafted tissues.
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Shu, Jian, Jun Ma, Xiameng Ren, Jian Wang, Yan Wang, Kun Zhang, Hanjie Yu, Xiangqian Guo et Zheng Li. « The Abnormal Glycopatterns of Salivary Glycoproteins in Esophageal Squamous Cell Carcinoma Patients ». Frontiers in Chemistry 9 (4 mars 2021). http://dx.doi.org/10.3389/fchem.2021.637730.

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Glycosylation is one of the most crucial posttranslational modifications of proteins, containing a remarkable amount of biological information. The alteration of glycosylation is closely associated with certain diseases. Exploring glyco-code in the development of diseases is a hot topic in recent years. Esophageal squamous cell carcinoma (ESCC) is the primary pathological histology in developing countries and a severe threat to human health. Although the glycan profiles in the blood samples of ESCC patients were analyzed using glycomic and glycoproteomic methods, the difference of salivary glycopatterns between healthy subjects and ESCC patients is not explicit yet. In the present study, ESCC patients (n = 16) and healthy volunteers (HVs, n = 25) were enrolled. The glycomic strategy combining lectin microarray and lectin blotting was employed to investigate and confirm the altered salivary glycopatterns. Datura stramonium (DSA) was selected to isolate the GlcNAc or Galβ1-4GlcNA-containing glycoproteins due to the distinct difference between ESCC patients and HVs. The N-glycans from DSA-enriched glycoproteins were released by PNGase F and further identified by MALDI-TOF/TOF-MS to obtain the precise structural information of the altered glycans. As a result, the glycopatterns recognized by 13 lectins (e.g., ECA, RCA120, and DSA) showed significant alterations in ESCC patients’ saliva. The ESCC patients showed higher levels of GalNAc and Gal, sialic acid, and GlcNAc expression profiles and lower levels of mannose and fucose expression profiles. The MALDI-TOF/TOF-MS results indicated that the proportion of the GlcNAc or Galβ1-4GlcNAc-containing N-glycans was increased in ESCC patients (79.04%) compared with HV (63.20%), which was consistent with the results of lectin microarrays. Our findings provide comprehensive information to understand the complex physiological changes in ESCC patients. And the altered salivary glycopatterns such as GlcNAc or Galβ1-4GlcNAc-containing N-glycans recognized by DSA might serve as potential biomarkers for the diagnosis of ESCC patients.
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Ren, Lihua, Xin Fang, Sachin Mulmi Shrestha, Qinghua Ji, Hui Ye, Yan Liang, Yang Liu, Yadong Feng, Jingwu Dong et Ruihua Shi. « LncRNA SNHG16 promotes development of oesophageal squamous cell carcinoma by interacting with EIF4A3 and modulating RhoU mRNA stability ». Cellular & ; Molecular Biology Letters 27, no 1 (11 octobre 2022). http://dx.doi.org/10.1186/s11658-022-00386-w.

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Abstract Background Numerous studies have revealed that long noncoding RNAs (lncRNAs) are closely related to the development of many diseases and carcinogenesis. However, their specific biological function and molecular mechanism in oesophageal squamous cell carcinoma (ESCC) remains unclear. Methods RNA-Seq was performed to determine the differential expressions of lncRNAs in ESCC, and the level of SNHG16 expression was detected in ESCC and intraepithelial neoplasia (IEN) samples. In vitro and in vivo experiments were performed to explore the role of SNHG16 and the interaction of EIF4A3 and Ras homologue family member U (RhoU) signalling. Results One hundred and seventy-five upregulated and 134 downregulated lncRNAs were identified by RNA-Seq. SNHG16 was highly expressed in ESCC and intraepithelial neoplasia (IEN) samples, and its expression level was correlated with tumour differentiation and T stage. Overexpression of SNHG16 can facilitate ESCC cell proliferation and metastasis. Mechanistically, we noticed that SNHG16 could bind RNA binding protein (RBP)-eukaryotic translation initiation factor (EIF4A3) and interact with it to form a complex. Importantly, the coalition of SNHG16 and EIF4A3 ultimately regulated Ras homologue family member U (RhoU). SNHG16 modulated RhoU expression by recruiting EIF4A3 to regulate the stability of RhoU mRNA. Knockdown of RhoU further alleviated the effect of the SNHG16 oncogene in ESCC cells. Conclusions The newly identified SNHG16–EIF4A3–RhoU signalling pathway directly coordinates the response in ESCC pathogenesis and suggests that SNHG16 is a promising target for potential ESCC treatment.
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Mitrović, Boško, Shir Lezerovich et Neta Sal-Man. « The Role of the Membrane-Associated Domain of the Export Apparatus Protein, EscV (SctV), in the Activity of the Type III Secretion System ». Frontiers in Microbiology 12 (3 août 2021). http://dx.doi.org/10.3389/fmicb.2021.719469.

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Diarrheal diseases remain a major public health concern worldwide. Many of the causative bacterial pathogens that cause these diseases have a specialized protein complex, the type III secretion system (T3SS), which delivers effector proteins directly into host cells. These effectors manipulate host cell processes for the benefit of the infecting bacteria. The T3SS structure resembles a syringe anchored within the bacterial membrane, projecting toward the host cell membrane. The entry port of the T3SS substrates, called the export apparatus, is formed by five integral membrane proteins. Among the export apparatus proteins, EscV is the largest, and as it forms a nonamer, it constitutes the largest portion of the export apparatus complex. While there are considerable data on the soluble cytoplasmic domain of EscV, our knowledge of its membrane-associated section and its transmembrane domains (TMDs) is still very limited. In this study, using an isolated genetic reporter system, we found that TMD5 and TMD6 of EscV mediate strong self-oligomerization. Substituting these TMDs within the full-length protein with a random hydrophobic sequence resulted in a complete loss of function of the T3SS, further suggesting that the EscV TMD5 and TMD6 sequences have a functional role in addition to their structural role as membrane anchors. As we observed only mild reduction in the ability of the TMD-exchanged variants to integrate into the full or intermediate T3SS complexes, we concluded that EscV TMD5 and TMD6 are not crucial for the global assembly or stability of the T3SS complex but are rather involved in promoting the necessary TMD–TMD interactions within the complex and the overall TMD orientation to allow channel opening for the entry of T3SS substrates.
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Lei, Ling-Ling, Xin Song, Xue-Ke Zhao, Rui-Hua Xu, Meng-Xia Wei, Lin Sun, Pan-Pan Wang et al. « Long-term effect of hospital volume on the postoperative prognosis of 158,618 patients with esophageal squamous cell carcinoma in China ». Frontiers in Oncology 12 (16 février 2023). http://dx.doi.org/10.3389/fonc.2022.1056086.

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BackgroundThe impact of hospital volume on the long-term survival of esophageal squamous cell carcinoma (ESCC) has not been well assessed in China, especially for stage I–III stage ESCC. We performed a large sample size study to assess the relationships between hospital volume and the effectiveness of ESCC treatment and the hospital volume value at the lowest risk of all-cause mortality after esophagectomy in China.AimTo investigate the prognostic value of hospital volume for assessing postoperative long-term survival of ESCC patients in China.MethodsThe date of 158,618 patients with ESCC were collected from a database (1973–2020) established by the State Key Laboratory for Esophageal Cancer Prevention and Treatment, the database includes 500,000 patients with detailed clinical information of pathological diagnosis and staging, treatment approaches and survival follow-up for esophageal and gastric cardia cancers. Intergroup comparisons of patient and treatment characteristics were conducted with the X2 test and analysis of variance. The Kaplan-Meier method with the log-rank test was used to draw the survival curves for the variables tested. A Multivariate Cox proportional hazards regression model was used to analyze the independent prognostic factors for overall survival. The relationship between hospital volume and all-cause mortality was assessed using restricted cubic splines from Cox proportional hazards models. The primary outcome was all-cause mortality.ResultsIn both 1973-1996 and 1997-2020, patients with stage I-III stage ESCC who underwent surgery in high volume hospitals had better survival than those who underwent surgery in low volume hospitals (both P<0.05). And high volume hospital was an independent factor for better prognosis in ESCC patients. The relationship between hospital volume and the risk of all-cause mortality was half-U-shaped, but overall, hospital volume was a protective factor for esophageal cancer patients after surgery (HR<1). The concentration of hospital volume associated with the lowest risk of all-cause mortality was 1027 cases/year in the overall enrolled patients.ConclusionHospital volume can be used as an indicator to predict the postoperative survival of ESCC patients. Our results suggest that the centralized management of esophageal cancer surgery is meaningful to improve the survival of ESCC patients in China, but the hospital volume should preferably not be higher than 1027 cases/year.Core tipHospital volume is considered to be a prognostic factor for many complex diseases. However, the impact of hospital volume on long-term survival after esophagectomy has not been well evaluated in China. Based on a large sample size of 158,618 ESCC patients in China spanning 47 years (1973-2020), We found that hospital volume can be used as a predictor of postoperative survival in patients with ESCC, and identified hospital volume thresholds with the lowest risk of death from all causes. This may provide an important basis for patients to choose hospitals and have a significant impact on the centralized management of hospital surgery.
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Li, Shu-Yang, Yoichi Yoshida, Eiichi Kobayashi, Masaaki Kubota, Tomoo Matsutani, Seiichiro Mine, Toshio Machida et al. « Serum anti-AP3D1 antibodies are risk factors for acute ischemic stroke related with atherosclerosis ». Scientific Reports 11, no 1 (29 juin 2021). http://dx.doi.org/10.1038/s41598-021-92786-9.

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AbstractAtherosclerosis has been considered as the main cause of morbidity, mortality, and disability worldwide. The first screening for antigen markers was conducted using the serological identification of antigens by recombinant cDNA expression cloning, which has identified adaptor-related protein complex 3 subunit delta 1 (AP3D1) as an antigen recognized by serum IgG antibodies of patients with atherosclerosis. Serum antibody levels were examined using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) using a recombinant protein as an antigen. It was determined that the serum antibody levels against AP3D1 were higher in patients with acute ischemic stroke (AIS), transient ischemic attack, diabetes mellitus (DM), cardiovascular disease, chronic kidney disease (CKD), esophageal squamous cell carcinoma (ESCC), and colorectal carcinoma than those in the healthy donors. The area under the curve values of DM, nephrosclerosis type of CKD, and ESCC calculated using receiver operating characteristic curve analysis were higher than those of other diseases. Correlation analysis showed that the anti-AP3D1 antibody levels were highly associated with maximum intima-media thickness, which indicates that this marker reflected the development of atherosclerosis. The results of the Japan Public Health Center-based Prospective Study indicated that this antibody marker is deemed useful as risk factors for AIS.
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Sun, Xiaoyun, Linxi Cheng et Yuhua Sun. « Autism-associated protein POGZ controls ESCs and ESC neural induction by association with esBAF ». Molecular Autism 13, no 1 (1 juin 2022). http://dx.doi.org/10.1186/s13229-022-00502-9.

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Abstract Background The POGZ gene has been found frequently mutated in neurodevelopmental disorders (NDDs), particularly autism spectrum disorder (ASD) and intellectual disability (ID). However, little is known about its roles in embryonic stem cells (ESCs), neural development and diseases. Methods We generated Pogz−/− ESCs and directed ESC differentiation toward a neural fate. We performed biochemistry, ChIP-seq, ATAC-seq, and bioinformatics analyses to understand the role of POGZ. Results We show that POGZ is required for the maintenance of ESC identity and the up-regulation of neural genes during ESC differentiation toward a neural fate. Genome-wide binding analysis shows that POGZ is primarily localized to gene promoter and enhancer regions. POGZ functions as both a transcriptional activator and repressor, and its loss leads to deregulation of differentiation genes, including neural genes. POGZ physically associates with the SWI-SNF (esBAF) chromatin remodeler complex, and together they modulate enhancer activities via epigenetic modifications such as chromatin remodeling and histone modification. During ESC neural induction, POGZ-mediated recruitment of esBAF/BRG1 and H3K27ac are important for proper expression of neural progenitor genes. Limitations The genotype and allele relevant to human neurodevelopmental disorders is heterozygous loss of function. This work is designed to study the effects of loss of POGZ function on ESCs and during ESC neural induction. Also, this work lacks of in vivo validation using animal models. Conclusions The data suggest that POGZ is both a transcription factor and a genome regulator, and its loss leads to defects in neural induction and neurogenesis.
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Castro, Betsy E., Rafael Rios, Lina P. Carvajal, Mónica L. Vargas, Mónica P. Cala, Lizeth León, Blake Hanson et al. « Multiomics characterization of methicillin-resistant Staphylococcus aureus (MRSA) isolates with heterogeneous intermediate resistance to vancomycin (hVISA) in Latin America ». Journal of Antimicrobial Chemotherapy, 2 novembre 2022. http://dx.doi.org/10.1093/jac/dkac363.

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Abstract Background Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) compromise the clinical efficacy of vancomycin. The hVISA isolates spontaneously produce vancomycin-intermediate Staphylococcus aureus (VISA) cells generated by diverse and intriguing mechanisms. Objective To characterize the biomolecular profile of clinical hVISA applying genomic, transcriptomic and metabolomic approaches. Methods 39 hVISA and 305 VSSA and their genomes were included. Core genome-based Bayesian phylogenetic reconstructions were built and alterations in predicted proteins in VISA/hVISA were interrogated. Linear discriminant analysis and a Genome-Wide Association Study were performed. Differentially expressed genes were identified in hVISA-VSSA by RNA-sequencing. The undirected profiles of metabolites were determined by liquid chromatography and hydrophilic interaction in six CC5-MRSA. Results Genomic relatedness of MRSA associated to hVISA phenotype was not detected. The change Try38 → His in Atl (autolysin) was identified in 92% of the hVISA. We identified SNPs and k-mers associated to hVISA in 11 coding regions with predicted functions in virulence, transport systems, carbohydrate metabolism and tRNA synthesis. Further, capABCDE, sdrD, esaA, esaD, essA and ssaA genes were overexpressed in hVISA, while lacABCDEFG genes were downregulated. Additionally, valine, threonine, leucine tyrosine, FAD and NADH were more abundant in VSSA, while arginine, glycine and betaine were more abundant in hVISA. Finally, we observed altered metabolic pathways in hVISA, including purine and pyrimidine pathway, CoA biosynthesis, amino acid metabolism and aminoacyl tRNA biosynthesis. Conclusions Our results show that the mechanism of hVISA involves major changes in regulatory systems, expression of virulence factors and reduction in glycolysis via TCA cycle. This work contributes to the understanding of the development of this complex resistance mechanism in regional strains.
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Rondón-Ayala, José A. « Cáncer hereditario de colon no polipósico asociado a adenocarcinoma de endometrio, piel actínica y consanguinidad. A propósito de un caso ». Bionatura 3, no 4 (15 novembre 2018). http://dx.doi.org/10.21931/rb/2018.03.04.10.

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