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OBJECTIVE To determine the prevalence of intra-patient inter-metastatic heterogeneity based on positron emission tomography (PET)/computed tomography (CT) in patients with metastatic castration-resistant prostate cancer (mCRPC) and to determine the prevalence of neuroendocrine disease in these patients and their eligibility for radioligand therapies (RLTs). PATIENTS AND METHODS This multicentre observational prospective clinical study will include 100 patients with mCRPC from five Canadian academic centres. Patients with radiological or biochemical progression and harbouring at least three metastases by conventional imaging will be accrued. Intra-patient inter-metastatic heterogeneity will be determined with triple-tracer imaging using fluorine-18 fluorodeoxyglucose (18 F-FDG), gallium-68-(68 Ga)-prostate-specific membrane antigen (PSMA)-617 and 68 Ga-DOTATATE, which are a glucose analogue, a PSMA receptor ligand and a somatostatin receptor ligand, respectively. The 68 Ga-PSMA-617 and 18 F-FDG PET/CT scans will be performed first. If at least one PSMA-negative/FDG-positive lesion is observed, an additional PET/CT scan with 68 Ga-DOTATATE will be performed. The tracer uptake of individual lesions will be assessed for each PET tracer and patients with lesions presenting discordant uptake profiles will be considered as having inter-metastatic heterogeneous disease and may be offered a biopsy. EXPECTED RESULTS The proposed triple-tracer approach will allow whole-body mCRPC characterisation, investigating the inter-metastatic heterogeneity in order to better understand the phenotypic plasticity of prostate cancer, including the neuroendocrine transdifferentiation that occurs during mCRPC progression. Based on 68 Ga-PSMA-617 or 68 Ga-DOTATATE PET positivity, the potential eligibility of patients for PSMA and DOTATATE-based RLT will be assessed. Non-invasive whole-body determination of mCRPC heterogeneity and transdifferentiation is highly innovative and might establish the basis for new therapeutic strategies. Comparison of molecular imaging findings with biopsies will also link metastasis biology to radiomic features. CONCLUSION This study will add novel, biologically relevant dimensions to molecular imaging: the non-invasive detection of inter-metastatic heterogeneity and transdifferentiation to neuroendocrine prostate cancer by using a multi-tracer PET/CT strategy to further personalise the care of patients with mCRPC.

YKL-40 (chitinase 3-like 1 gene; CHI3L1) is an inflammatory marker that is increased in the blood of patients with inflammatory diseases, including cystic fibrosis (CF). The objective of our study was to explore the relationship between circulating levels of YKL-40, selected CHI3L1 single nucleotide polymorphisms (SNPs) and the severity of CF disease.A prospective cohort of 188 adult patients with CF was established in 2015. Blood samples and clinical data were collected over 2 years to analyze the circulating levels of YKL-40 and to genotype selected CHI3L1 SNPs. We also looked for an association between these factors and clinical parameters.We found that according to the serum YKL-40 concentration, the patients could be categorized into two distinct groups: low and high YKL-40. Compared to the patients in the low YKL-40 group, the patients in the high YKL-40 group had lower lung function (P0.001), a higher proportion of delF508 homozygote mutations (P= 0.027) and dysglycemia (P= 0.015). They were also more colonized with Pseudomonas aeruginosa (P= 0.003) and required more frequent antibiotic intravenous courses (P0.001). We also observed that patients expressing the C/C-rs4950928 genotype had higher levels of YKL-40 in their blood and were more frequently dysglycemic.Our study suggests that YKL-40 could be a potential biomarker of CF disease severity. Furthermore, the CHI3L1 rs4950928 SNP could be a susceptible gene that could be used by CF health professionals to identify patients who are the most at risk of having a severe clinical profile.

Background Dead time may affect the accuracy of quantitative SPECT (QPSECT), and thus of dosimetry. The aim of this study was to quantify the effect of dead time on 177Lu-QSPECT and renal dosimetry following peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumours. Methods QSPECT/CT was performed on days 1 and 3 during 564 personalized 177Lu-octreotate cycles in 166 patients. The dead-time data for each scanning time point was compiled. The impact of not correcting QSPECT for the dead time was assessed for the kidney dosimetry. This was also estimated for empiric PRRT by simulating in our cohort a regime of 7.4 GBq/cycle. Results The probability to observe a larger dead time increased with the injected activity. A dead-time loss greater than 5% affected 14.4% and 5.7% of QSPECT scans performed at days 1 and 3, respectively. This resulted in renal absorbed dose estimates that would have been underestimated by more than 5% in 5.7% of cycles if no dead-time correction was applied, with a maximum underestimation of 22.1%. In the simulated empiric regime, this potential dose underestimation would have been limited to 6.2%. Conclusion Dead-time correction improves the accuracy of dosimetry in 177Lu radionuclide therapy and is warranted in personalized PRRT.

Background Accurate QSPECT is crucial in dosimetry-based, personalized radiopharmaceutical therapy with 177Lu and other radionuclides. We compared the quantitative performance of three NaI(Tl)-crystal SPECT/CT systems equipped with low-energy high-resolution collimators from two vendors (Siemens Symbia T6; GE Discovery 670 and NM/CT 870 DR). Methods Using up to 14 GBq of 99mTc in planar mode, we determined the calibration factor and dead-time constant under the assumption that these systems have a paralyzable behaviour. We monitored their response when one or both detectors were activated. QSPECT capability was validated by SPECT/CT imaging of a customized NEMA phantom containing up to 17 GBq of 99mTc. Acquisitions were reconstructed with a third-party ordered subset expectation maximization algorithm. Results The Siemens system had a higher calibration factor (100.0 cps/MBq) and a lower dead-time constant (0.49 μs) than those from GE (75.4–87.5 cps/MBq; 1.74 μs). Activities of up to 3.3 vs. 2.3–2.7 GBq, respectively, were quantifiable by QSPECT before the observed count rate plateaued or decreased. When used in single-detector mode, the QSPECT capability of the former system increased to 5.1 GBq, whereas that of the latter two systems remained independent of the detectors activation mode. Conclusion Despite similar hardware, SPECT/CT systems’ response can significantly differ at high count rate, which impacts their QSPECT capability in a post-therapeutic setting.

The chitinase-3-like protein 1, also known as YKL-40, is an inflammatory marker increased in blood of patients with cystic fibrosis (CF). Systemic levels of YKL-40 are increased in dysglycemic patients with CF. Our objective is to determine if YKL-40 is expressed and released by CF neutrophils. We also assessed if specific stimulus, such as glucose and lipopolysaccharide (LPS), can induce the secretion of YKL-40. Neutrophil cells of healthy adults and patients with CF were isolated. Immunostaining of whole blood and neutrophils was done. CF and healthy neutrophils were cultured with either LPS or varying concentrations of glucose. YKL-40 protein was measured using specific immunoassay ELISA. Isolated neutrophil cells from 11 patients with CF (32.3 ± 8.0 years) were compared to five age-matched healthy individuals (28.3 ± 5.5 years). Although there is a significant increase in the concentration of YKL-40 in CF neutrophils compared to healthy neutrophils (P = 0.027), the spontaneous release of YKL-40 into the media is similar in CF and healthy neutrophils. CF neutrophils stimulated with LPS or glucose do not stimulate the release of YKL-40 (P = 0.995 for glucose and P = 0.624 for LPS). CF neutrophils have higher intracellular level of YKL-40 than neutrophils from healthy volunteers, but they do not release more YKL-40 when stimulated with exogenous stimulus. These results suggest that the increased levels of circulating YKL-40 in CF patients might originate from another cellular source.

Glucose abnormality and diabetes are the most common comorbidities in cystic fibrosis (CF). Combined (aerobic and resistance) exercise program in type 2 patients with diabetes demonstrated an improvement of glycemic control. The aim of the study was to determine whether a combined exercise program is beneficial to improve plasma glucose at 2 h of the oral glucose tolerance test in CF.Eighteen adults with CF with glucose abnormality were recruited (Clinicaltrial.gov: NTC02127957), and 17 were randomly assigned to a control or exercise group for 12 wk. V˙O2max, oral glucose tolerance test, muscular endurance and strength, and quality of life were measured pre- and postintervention.Fourteen participants completed the protocol. Patients in the exercise group improved significantly their 2-h plasma glucose values (-2.34 ± 1.26 mmol·L, P0.007, confidence interval = 99.22%) and presented a reduction of 17.2% (P0.05) in total glucose excursion. No significant change for other parameters was observed.A combined exercise program improves glycemic control in CF.

RGS2 is a key modulator of stress in human airway epithelial cells, especially of hyperresponsiveness and mucin hypersecretion, both of which are features of cystic fibrosis (CF). Because its expression can be modulated through the DNA methylation pathway, we hypothesize that RGS2 is downregulated by DNA hypermethylation in CF airway epithelial cells. This downregulation would then lead to an enhanced inflammatory response. We demonstrated RGS2 transcript and protein downregulation in cultured airway epithelial cells from patients with CF and validated our findings in two CF epithelial cell lines. A methylated DNA immunoprecipitation array showed the presence of methylated cytosine on 13 gene promoters in CF. Among these genes, we confirmed that the RGS2 promoter was hypermethylated by using bisulfite conversion coupled with a methylation-specific PCR assay. Finally, we showed that downregulation of RGS2 in non-CF cells increased the expression of S100A12, a proinflammatory marker. These results highlight the importance of epigenetic regulation in gene expression in CF and show that RGS2 might modulate the inflammatory response in CF through DNA methylation control.

During the last decades, the development of ever more powerful genetic, molecular and omic approaches has provided plant pathologists with a wide array of experimental tools for elucidating the intricacies of plant-pathogen interactions and proposing new control strategies. In the case of the Dutch elm disease (DED) pathosystem, these tools have been applied for advancing knowledge of the host (Ulmus spp.) and the causal agents (Ophiostoma ulmi, O. novo-ulmi and O. himal-ulmi). Genetic and molecular analyses have led to the identification, cloning and characterization of a few genes that contribute to parasitic fitness in the pathogens. Quantitative PCR and high-throughput methods, such as expressed sequence tag analysis, have been used for measuring gene expression and identifying subsets of elm genes that are differentially expressed in the presence of O. novo-ulmi. These analyses have also helped identify genes that were differentially expressed in DED fungi grown under defined experimental conditions. Until recently, however, functional analysis of the DED fungi was hampered by the lack of protocols for efficient gene knockout and by the unavailability of a full genome sequence. While the selective inactivation of Ophiostoma genes by insertional mutagenesis remains a challenge, an alternative approach based on RNA interference is now available for down-regulating the expression of targeted genes. In 2013, the genome sequences of O. ulmi and O. novo-ulmi were publicly released. The ongoing annotation of these genomes should spark a new wave of interest in the DED pathosystem, as it should lead to the formal identification of genes modulating parasitic fitness. A better understanding of DED, however, also requires that omic approaches are applied to the study of the other biotic components of this pathosystem.

YKL-40, a chitinase-like protein, is a biomarker for type 1 and type 2 diabetes prognosis. We hypothesized that YKL-40 protein levels are elevated in CF patients with dysglycemia.Seventeen healthy control subjects and 66 CF patients were prospectively recruited and subjected to an oral glucose tolerance test. In all participants, fasting serum YKL-40 was compared between control and CF patients and between normal glucose-tolerant patients (NG-CF) and CF patients with dysglycemia (DG-CF). A Botnia clamp procedure was performed on a subset of patients for each group to determine the impact of acute increases of either glucose or insulin on YKL-40 concentration.CF patients had higher serum YKL-40 values than the controls (113 [49;288] vs. 38 [30;50] ng/ml, p0.001). YKL-40 concentrations in CF patients were mainly increased in the DG-CF group, who had significantly higher values: 213 [93;383] vs. 67 [27;97] ng/ml in the NG-CF group, p0.001). No significant modulation of YKL-40 concentration was observed in serum of CF (NG or DG-CF) or non-CF patients, after acute exposure to glucose or insulin.Higher serum YKL-40 levels in CF patients are significantly associated with dysglycemia. The increase in YKL-40 is potentially associated with an inflammatory response resulting from chronic glucose intolerance or CF disease evolution.

Although cystic fibrosis (CF) pathophysiology is explained by a defect in CF transmembrane conductance regulator (CFTR) protein, the broad spectrum of disease severity is the consequence of environmental and genetic factors. Among them, oxidative stress has been demonstrated to play an important role in the evolution of this disease, with susceptibility to oxidative damage, decline of pulmonary function, and impaired lung antioxidant defense. Although oxidative stress has been implicated in the regulation of inflammation, its molecular outcomes in CF cells remain to be evaluated. To address the question, we compared the gene expression profile in NuLi-1 cells with wild-type CFTR and CuFi-1 cells homozygous for ΔF508 mutation cultured at air-liquid interface. We analyzed the transcriptomic response of these cell lines with microarray technology, under basal culture conditions and after 24 h oxidative stress induced by 15 μM 2,3-dimethoxy-1,4-naphtoquinone. In the absence of oxidative conditions, CuFi-1 gene profiling showed typical dysregulated inflammatory responses compared with NuLi-1. In the presence of oxidative conditions, the transcriptome of CuFi-1 cells reflected apoptotic transcript modulation. These results were confirmed in the CFBE41o- and corrCFBE41o- cell lines as well as in primary culture of human CF airway epithelial cells. Altogether, our data point to the influence of oxidative stress on cell survival functions in CF and identify several genes that could be implicated in the inflammation response observed in CF patients.

Nitric oxide (NO) plays an important role in innate host defense and inflammation. In response to infection, NO is generated by inducible nitric oxide synthase (iNOS), a gene product whose expression is highly modulated by different stimuli, including lipopolysaccharide (LPS) from gram-negative bacteria. We reported recently that LPS from Pseudomonas aeruginosa altered Na+transport in alveolar epithelial cells via a suramin-dependent process, indicating that LPS activated a purinergic response in these cells. To further study this question, in the present work, we tested whether iNOS mRNA and protein expression were modulated in response to LPS in alveolar epithelial cells. We found that LPS induced a 12-fold increase in iNOS mRNA expression via a transcription-dependent process in these cells. iNOS protein, NO, and nitrotyrosine were also significantly elevated in LPS-treated cells. Ca2+chelation and protein kinase C (PKCα-β1) inhibition suppressed iNOS mRNA induction by LPS, implicating Ca2+-dependent PKC signaling in this process. LPS evoked a significant increase of extracellular ATP. Because PKC activation is one of the signaling pathways known to mediate purinergic signaling, we evaluated the hypothesis that iNOS induction was ATP dependent. Although high suramin concentration inhibited iNOS mRNA induction, the process was not ATP dependent, since specific purinergic receptor antagonists could not inhibit the process. Altogether, these findings demonstrate that iNOS expression is highly modulated in alveolar epithelial cells by LPS via a Ca2+/PKCα-β1 pathway independent of ATP signaling.

Background. Chronic granulomatous disease is a rare inherited disorder of the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The clinical course of the disease is marked by recurrent infections, includingBurkholderia cepacia complexinfection.Case Report. Here we report the case of a 21-year-old male hospitalized for aBurkholderia cepacia complexpneumonia. Despite the broad spectrum antibiotic treatment, fever continued and patient’s condition worsened. Anemia and thrombocytopenia developed together with hypofibrinogenemia. The patient died of multiple organ dysfunction 17 days after his admission. Autopsy revealed hemophagocytosis, suggesting the diagnosis of acquired hemophagocytic lymphohistiocytosis. DNA analysis showed a deletion in the p47phox gene, confirming the diagnosis of autosomal recessive chronic granulomatous disease.Discussion. In addition to chronic granulomatous disease, recent findings have demonstrated thatBurkholderia cepacia complexcan decrease activity of the NADPH oxidase. Interestingly, hemophagocytic lymphohistiocytosis is characterized by an impaired function of the T-cell mediated inflammation which is partly regulated by the NADPH oxidase. Physicians should therefore pay particular attention to this deadly association.

The mobility of transposable elements (TEs) can contribute to genome plasticity, under- or over-expression of genes and ectopic recombination. The data collected in this study provide evidence of stress-induced mobility of OPHIO1 and OPHIO2 transposons, recently detected in Ophiostoma ulmi and O. novo-ulmi, the causal agents of Dutch elm disease (DED). The analyses of OPHIO UTRs and TIRs indicated the presence of two potential binding site motifs and a heat shock protein (hsp) promoter which could be involved in the mobility of OPHIO1 following a heat shock stress. The exact position of the hsp promoter was determined by 5' RACE PCR. After confirmation of the expression by RT-PCR of both OPHIO1 and OPHIO2 transposases in the absence of stress factors, we tested two experimental procedures to induce mobility of OPHIO TEs: (1) an exogenous (cloned) copy of OPHIO1 was introduced into the O. novo-ulmi subsp. americana strain W2 (OPHIO1 free strain) to give mutant strain W2:OPHIO1. After exposure of W2:OPHIO1 to a 55 degrees C heat shock treatment, some of the survivors showed signs of incomplete transposition (excision without reinsertion) of OPHIO1. (2) The O. novo-ulmi subsp. novo-ulmi strain AST27, introgressed from O. ulmi and carrying a distinct endogenous copy of OPHIO2 (OPHIO2-int.), was subjected to a series of abiotic stress treatments. Although a promoter sequence could not be identified, both exposures to UV light and to a 4 degrees C cold treatment caused perfect excision of OPHIO2-int. In contrast to OPHIO1, heat shock stress did not induce OPHIO2-int. mobility. Taken together, these results allow us to hypothesize a potential interspecific invasion of OPHIO transposons due to their mobility in Ophiostoma spp.

Suppression subtractive hybridization cDNA libraries were prepared from asexual synnemata (S-lib) and sexual perithecia (P-lib) fruiting bodies of the Dutch elm disease pathogen Ophiostoma novo-ulmi subsp. novo-ulmi isolate H327 (mating-type MAT1-1) consisting of 630 and 401 cDNA clones, respectively. Both libraries were differentially screened in duplicate with forward and reverse subtracted probes. Up-regulated S-lib transcripts included those with homologies to phosphoenolpyruvate carboxykinase and aquaporin. Up-regulated P-lib transcripts included those with homologies to aspartyl proteinase, DNA lyase 2, and part of a mating-type (MAT) protein containing a DNA-binding domain of the high-mobility group (HMG) type. Phylogenetic analyses of HMG domains present within the putative O. novo-ulmi MAT protein and within MAT1-1-3 and MAT1-2-1 proteins of other ascomycete fungi identified the O. novo-ulmi protein as a homologue of the MAT1-1-3 protein, which represents part of the so far uncharacterized O. novo-ulmi MAT1-1 idiomorph. Reverse transcription – quantitative real-time PCR indicated up-regulation of the MAT1-1-3 homologue in O. novo-ulmi perithecia and synnemata. The present work identifies, for the first time, proteins involved in the formation of asexual and sexual fruiting bodies in O. novo-ulmi and should be of interest to researchers concerned with reproduction, mating type, and sexuality of filamentous ascomycete fungi.

To identify novel pathways that could modulate epithelial ion transport in CF, we used a system biology approach to identify genes that are differentially expressed in CF and Non-CF epithelial cells. Data analysis showed that expression of chitinase 3 like 1 gene (CHI3L1 also known as YKL-40), a secreted glycoprotein, was particularly elevated in CF epithelial cells. Moreover, we observed a higher concentration of circulating YKL-40 in dysglycemia CF patients. We demonstrated that a fasting YKL-40 concentration of 102 ng/mL was predictive of abnormal OGTT with a sensitivity of 74% and specificity of 83%, corresponding to a positive likelihood ratio weighted by prevalence of 7.75. We also observed a relationship between YKL-40 and inflammatory cytokines (especially IL-8) in the circulation, reflecting that YKL-40 participates in a systemic inflammatory response associated with cystic fibrosis. In order to explore the role of YKL-40-induced pathway, we combined YKL-40 coimmunoprecipitation and surface receptors protein arrays either on CF epithelial ( CFBE41o -) or macrophage ( THP-1 ) cell lines. Results demonstrated the presence of the CD36 scavenger receptor, on both cell types. CD36, which is able to bind to thrombospondin, oxidized LDL (oxLDL) and induces inflammatory responses, is also a marker of macrophage differentiation/activation. THP-1 monocyte-derived macrophages treated by 300 ng/µl of YKL-40 demonstrated an upregulation of inflammatory transcripts (IL6, IL10 and S100A12). We will present and discussed our results on the interaction between YKL-40, CD36 and inflammation in CF.

Transposable elements (TEs) are fundamental components of eukaryotic genomes and can contribute in various ways to genome plasticity and evolution. We describe here the first three DNA transposons in the Dutch elm disease (DED) pathogens Ophiostoma ulmi and O. novo-ulmi, named OPHIO1, OPHIO2 and OPHIO3. We demonstrate that OPHIO transposons, which show high homology to Fot1/pogo TEs within the Tc1/mariner superfamily, have different distribution patterns and specificity in the DED fungi and that interspecific hybrids could act as genetic bridges for transmission of TEs between closely related fungal species. OPHIO3 was found to have undergone repeat-induced point mutations (RIP). We have also developed a complementary method to Margolin’s ratios based on the computation of cumulative transition scores (CTS) in order to visualize rapidly RIP signatures on individual DNA strands of OPHIO transposons and TEs found in other ascomycete fungi.

Purpose: Cystic Fibrosis (CF) is the most common genetic disorder and, with improved survival, glucose abnormalities have emerged as a major comorbidity. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a regulator of plasma LDL-cholesterol homeostasis, is associated with lipid and glucose metabolism in healthy individuals. Here we report on the link between PCSK9 and markers of metabolism in CF. Methods: Cross-sectional analysis was performed on CF patients (≥ 18 years, N=94) from the Montreal Cohort, without known diabetes, and on healthy individuals (N=19). The levels of PCSK9 and lipid markers were quantified and all subjects underwent a 2 h oral glucose tolerance test. Results: No significant differences in PCSK9 levels were found between healthy individuals and patients with CF, or between the groups with different degrees of glucose tolerance. No association was found between PCSK9 and markers of lipid metabolism; however, a positive correlation was found between PCSK9 and total insulin secretion and a negative one with insulin sensitivity in CF patients who had normal glucose tolerance. Conclusion: Circulating levels of PCSK9 in the CF population are comparable to those in the healthy population. There are no associations between PCSK9 levels and either glucose or lipid homeostasis parameters. Nevertheless, a statistically significant link was observed between PCSK9 and markers of insulin homeostasis, solely in CF patients who presented normal glucose tolerance. Further exploration of the relationship between PCSK9 and insulin homeostasis in CF patients with normal glucose tolerance is warranted.

The invasive fungal pathogens Ophiostoma ulmi and O. novo-ulmi have caused two successive pandemics of Dutch elm disease since the beginning of the 20th century. In nature, the highly aggressive O. novo-ulmi may hybridize with the less aggressive O. ulmi. Growth rate and molecular analyses were conducted on an unusual, moderately aggressive O. novo-ulmi isolate, AST27, carrying an introgressed pathogenicity gene, Pat1-m; on highly aggressive O. novo-ulmi isolate H327; on O. ulmi isolates Q412T and W9; and on progeny from laboratory crosses between H327 and AST27. Genetic analysis indicated that the Pat1 and Mat1 (mating type) loci were in different linkage groups corresponding to O. novo-ulmi H327 chromosomes 1 and 2, respectively. Most of the molecular differences between the nuclear genomes of H327 and AST27 occurred in the vicinity of Pat1 and Mat1. In addition, two putative quanti-tative trait loci, Mgr1 and Mgr2, which influence mycelial growth rate at 21°C and 28°C, the optima for O. novo-ulmi and O. ulmi, were linked to Mat1 and Pat1, respectively., Les champignons pathogènes envahissants Ophiostoma ulmi et O. novo-ulmi ont causé deux pandémies successives de maladie hollandaise de l’orme depuis le début du 20e siècle. On a mesuré la croissance et procédé à des analyses moléculaires chez l’isolat O. novo-ulmi AST27, modérément agressif et chez lequel le gène de pathogénie Pat1-m est introgressé; chez l’isolat O. novo-ulmi H327; chez les isolats O. ulmi Q412T et W9; ainsi que chez les descendants de croisements dirigés entre les isolats H327 et AST27. Les analyses génétiques indiquent que les loci Pat1 et Mat1 (type sexuel) sont situés sur des groupes de liaison différents qui correspondent respectivement aux chromosomes 1 et 2. Les différences moléculaires entre les génomes nucléaires des souches H327 et AST27 se retrouvent majoritairement dans le voisinage de Pat1 et de Mat1. De plus, deux loci présumés de caractères quantitatifs, Mgr1 et Mgr2, qui influencent la croissance mycélienne à 21 °C et à 28 °C (températures optimales pour O. novo-ulmi et O. ulmi) sont liés respectivement à Mat1 et à Pat1.