Diverse NLR immune receptors activate defence via the RPW8-NLR NRG1

Most land plant genomes carry genes that encode RPW8-NLR Resistance (R) proteins. Angiosperms carry two RPW8-NLR subclasses: ADR1 and NRG1. ADR1s act as 'helper' NLRs for multiple TIR- and CC-NLR R proteins in Arabidopsis. In angiosperm families, NRG1 co-occurs with TIR-NLR Resistance (R) genes. We tested whether NRG1 is required for signalling of multiple TIR-NLRs. Using CRISPR mutagenesis, we obtained an nrg1a-nrg1b double mutant in two Arabidopsis accessions, and an nrg1 mutant in Nicotiana benthamiana. These mutants are compromised in signalling of all TIR-NLRs tested, including WRR4A, WRR4B, RPP1, RPP2, RPP4 and the pairs RRS1/RPS4, RRS1B/RPS4B, CHS1/SOC3 and CHS3/CSA1. In Arabidopsis, NRG1 is required for the hypersensitive cell death response (HR) and full oomycete resistance, but not for salicylic acid induction or bacterial resistance. By contrast, nrg1 loss of function does not compromise the CC-NLR R proteins RPS5 and MLA. RPM1 and RPS2 (CC-NLRs) function is slightly compromised in an nrg1 mutant. Thus, NRG1 is required for full TIR-NLR function and contributes to the signalling of some CC-NLRs. Some NRG1-dependent R proteins also signal partially via the NRG1 sister clade, ADR1. We propose that some NLRs signal via NRG1 only, some via ADR1 only and some via both or neither

Autoimmunity conferred by chs3-2D relies on CSA1, its adjacent TIR-NB-LRR encoding neighbour

Plant innate immunity depends on the function of a large number of intracellular immune receptor proteins, the majority of which are structurally similar to mammalian nucleotidebinding oligomerization domain (NOD)-like receptor (NLR) proteins. CHILLING SENSITIVE 3 (CHS3) encodes an atypical Toll/Interleukin 1 Receptor (TIR)-type NLR protein with an additional Lin-11, Isl-1 and Mec-3 (LIM) domain at its C-terminus. The gain-of-function mutant allele chs3-2D exhibits severe dwarfism and constitutively activated defense responses, including enhanced resistance to virulent pathogens, high defence marker gene expression, and salicylic acid accumulation. To search for novel regulators involved in CHS3-mediated immune signaling, we conducted suppressor screens in the chs3-2D and chs3-2D pad4-1 genetic backgrounds. Alleles of sag101 and eds1-90 were isolated as complete suppressors of chs3-2D, and alleles of sgt1b were isolated as partial suppressors of chs3-2D pad4-1. These mutants suggest that SAG101, EDS1-90, and SGT1b are all positive regulators of CHS3-mediated defense signaling. Additionally, the TIR-type NLR-encoding CSA1 locus located genomically adjacent to CHS3 was found to be fully required for chs3-2D-mediated autoimmunity. CSA1 is located 3.9kb upstream of CHS3 and is transcribed in the opposite direction. Altogether, these data illustrate the distinct genetic requirements for CHS3-mediated defense signaling

Transgressive segregation reveals mechanisms of Arabidopsis immunity to Brassica-infecting races of white rust (Albugo candida)

Arabidopsis thaliana accessions are universally resistant at the adult leaf stage to white rust (Albugo candida) races that infect the crop species Brassica juncea and Brassica oleracea. We used transgressive segregation in recombinant inbred lines to test if this apparent species-wide (nonhost) resistance in A. thaliana is due to natural pyramiding of multiple Resistance (R) genes. We screened 593 inbred lines from an Arabidopsis multiparent advanced generation intercross (MAGIC) mapping population, derived from 19 resistant parental accessions, and identified two transgressive segregants that are susceptible to the pathogen. These were crossed to each MAGIC parent, and analysis of resulting F2 progeny followed by positional cloning showed that resistance to an isolate of A. candida race 2 (Ac2V) can be explained in each accession by at least one of four genes encoding nucleotide-binding, leucine-rich repeat (NLR) immune receptors. An additional gene was identified that confers resistance to an isolate of A. candida race 9 (AcBoT) that infects B. oleracea. Thus, effector-triggered immunity conferred by distinct NLR-encoding genes in multiple A. thaliana accessions provides species-wide resistance to these crop pathogens

Histone deacetylase adaptation in single ventricle heart disease and a young animal model of right ventricular hypertrophy.

BackgroundHistone deacetylase (HDAC) inhibitors are promising therapeutics for various forms of cardiac diseases. The purpose of this study was to assess cardiac HDAC catalytic activity and expression in children with single ventricle (SV) heart disease of right ventricular morphology, as well as in a rodent model of right ventricular hypertrophy (RVH).MethodsHomogenates of right ventricle (RV) explants from non-failing controls and children born with a SV were assayed for HDAC catalytic activity and HDAC isoform expression. Postnatal 1-day-old rat pups were placed in hypoxic conditions, and echocardiographic analysis, gene expression, HDAC catalytic activity, and isoform expression studies of the RV were performed.ResultsClass I, IIa, and IIb HDAC catalytic activity and protein expression were elevated in the hearts of children born with a SV. Hypoxic neonatal rats demonstrated RVH, abnormal gene expression, elevated class I and class IIb HDAC catalytic activity, and protein expression in the RV compared with those in the control.ConclusionsThese data suggest that myocardial HDAC adaptations occur in the SV heart and could represent a novel therapeutic target. Although further characterization of the hypoxic neonatal rat is needed, this animal model may be suitable for preclinical investigations of pediatric RV disease and could serve as a useful model for future mechanistic studies

A species-wide inventory of NLR genes and alleles in Arabidopsis thaliana

Infectious disease is both a major force of selection in nature and a prime cause of yield loss in agriculture. In plants, disease resistance is often conferred by nucleotide-binding leucine-rich repeat (NLR) proteins, intracellular immune receptors that recognize pathogen proteins and their effects on the host. Consistent with extensive balancing and positive selection, NLRs are encoded by one of the most variable gene families in plants, but the true extent of intraspecific NLR diversity has been unclear. Here, we define a nearly complete species-wide pan-NLRome in Arabidopsis thaliana based on sequence enrichment and long-read sequencing. The pan-NLRome largely saturates with approximately 40 well-chosen wild strains, with half of the pan-NLRome being present in most accessions. We chart NLR architectural diversity, identify new architectures, and quantify selective forces that act on specific NLRs and NLR domains. Our study provides a blueprint for defining pan-NLRomes

How scientists and physicians use Twitter during a medical congress

OBJECTIVES: During medical congresses Twitter allows discussions to disseminate beyond the congress hall and reach a wider audience. Insights into the dynamics of social media interactions during congresses, dissemination of scientific information and the determinants of a successful tweet may allow us to better understand social media's role in science communication. METHODS: We retrospectively extracted social media data during the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 2017 and 2018 using NodeXL. We compared social media activity during these two congresses. Subsequently, we conducted in-depth analyses to identify the components of a successful tweet and multivariable analysis to assess independent factors associated with retweet activity. RESULTS: In 2018, approximately 13,000 delegates attended ECCMID, but only 591 Twitter accounts actively tweeted about the congress. Although fewer tweets were posted in 2018 compared to 2017 (4,213 vs 4,657, respectively), ECCMID2018 generated a 63% increase in the total number of retweets (p <0.001). According to multivariable logistic regression analysis, using multimedia, URL or hashtags and mentioning other Twitter account(s) were independently associated with retweet success. Mentioning of other users and use of multimedia were the only consistent predictors of retweets irrespective of the number of followers. CONCLUSIONS: A substantial increase in retweet activity and a modest increase in the number of influential Twitter accounts were observed between two successive congresses. Dissemination of scientific messages is more successful when connected accounts are actively involved in social media activity, and social media posts constitute the right combination of components.PostprintPeer reviewe

Effect of harvest time on physicochemical quality parameters, oxidation stability, and volatile compounds of extra virgin olive oil

The aim of this study was to determine the changes in some physicochemical properties of olives (fruit weight, water content and oil content) and olive oils (total chlorophyll, carotenoid, pheophytin a, peroxide value and free acidity), and in the chemical properties (fatty acids, tocopherols, phenolics, oxidation stability and volatile profiles) of oils during ripening.Ripening indices (RI) of olive samples were 1.93 (unripe), 4.28 (ripe) and 5.89 (overripe). Most of the mentioned features changed with ripening. During ripening there was a sharp decrease in total chlorophyll, carotenoid and pheophytin a contents. An increase in oleic and linoleic acids and a decrease in palmitic acid were found in the fatty acid composition. Olive oils showed strong relations among oxidation stability, tocopherol content, total phenols content, and antiradical actvity of phenol extracts and these parameters decreased with maturation. Nevertheless, higher amounts of trans-2-hexenal were found in the oil from ripe olives than from unripe and overripe olives. On the other hand, the highest concentration of hexanal was found in the oil from overripe olives.In general, significant differences were observed in fruit weight, pigments, free acidity, fatty acid, tocopherol, and total phenolics contents, radical scavenger activity, oxidation stability, phenolic profile and volatile profile between the olive oils from the Gemlik cultivar at different stages of maturation

Common telomerase reverse transcriptase promoter mutations in hepatocellular carcinomas from different geographical locations

AIM: To determine the mutation status of human telomerase reverse transcriptase gene (TERT ) promoter region in hepatocellular carcinoma (HCC) from different geographical regions. METHODS: We analyzed the genomic DNA sequences of 59 HCC samples comprising 15 cell lines and 44 primary tumors, collected from patients living in Asia, Europe and Africa. We amplified a 474 bp DNA fragment of the promoter region of TERT gene including the 1295228 and 1295250 sequence of chromosome 5 by using PCR. Amplicons were then sequenced by Sanger technique and the sequence data were analyzed with by using DNADynamo software in comparison with wild type TERT gene sequence as a reference. RESULTS: The TERT mutations were found highly frequent in HCC. Eight of the fifteen tested cell lines displayed C228T mutation, and one had C250T mutation with a mutation frequency up to 60%. All of the mutations were heterozygous and mutually exclusive. Ten out of forty-four tumors displayed C228T mutation, and additional five tumors had C250T mutation providing evidence for mutation frequency of 34% in primary tumors. Considering the geographic origins of HCC tumors tested, TERT promoter mutation frequencies were higher in African (53%), when compared to non-African (24%) tumors (P = 0.056). There was also a weak inverse correlation between TERT promoter mutations and murine double minute 2 single nucleotide polymorphism 309 TG polymorphism (P = 0.058). Mutation frequency was nearly two times higher in established HCC cell lines (60%) compared to the primary tumors (34%). CONCLUSION: TERT promoter is one of most frequent mutational targets in liver cancer, and hepatocellular carcinogenesis is highly associated with the loss of telomere-dependent cellular senescence control. © The Author(s) 2015