Genome analysis of the necrotrophic fungal pathogens Sclerotinia sclerotiorum and Botrytis cinerea

Sclerotinia sclerotiorum and Botrytis cinerea are closely related necrotrophic plant pathogenic fungi notable for their wide host ranges and environmental persistence. These attributes have made these species models for understanding the complexity of necrotrophic, broad host-range pathogenicity. Despite their similarities, the two species differ in mating behaviour and the ability to produce asexual spores. We have sequenced the genomes of one strain of S. sclerotiorum and two strains of B. cinerea. The comparative analysis of these genomes relative to one another and to other sequenced fungal genomes is provided here. Their 38–39 Mb genomes include 11,860–14,270 predicted genes, which share 83% amino acid identity on average between the two species. We have mapped the S. sclerotiorum assembly to 16 chromosomes and found large-scale co-linearity with the B. cinerea genomes. Seven percent of the S. sclerotiorum genome comprises transposable elements compared t

A Randomized Controlled Trial Comparing the Effects of Counseling and Alarm Device on HAART Adherence and Virologic Outcomes

Michael Chung and colleagues show that intensive early adherence counseling at HAART initiation resulted in sustained, significant impact on adherence and virologic treatment failure, whereas use of an alarm device had no effect

Genomic Analysis of the Necrotrophic Fungal Pathogens Sclerotinia sclerotiorum and Botrytis cinerea

Sclerotinia sclerotiorum and Botrytis cinerea are closely related necrotrophic plant pathogenic fungi notable for their wide host ranges and environmental persistence. These attributes have made these species models for understanding the complexity of necrotrophic, broad host-range pathogenicity. Despite their similarities, the two species differ in mating behaviour and the ability to produce asexual spores. We have sequenced the genomes of one strain of S. sclerotiorum and two strains of B. cinerea. The comparative analysis of these genomes relative to one another and to other sequenced fungal genomes is provided here. Their 38–39 Mb genomes include 11,860–14,270 predicted genes, which share 83% amino acid identity on average between the two species. We have mapped the S. sclerotiorum assembly to 16 chromosomes and found large-scale co-linearity with the B. cinerea genomes. Seven percent of the S. sclerotiorum genome comprises transposable elements compared to <1% of B. cinerea. The arsenal of genes associated with necrotrophic processes is similar between the species, including genes involved in plant cell wall degradation and oxalic acid production. Analysis of secondary metabolism gene clusters revealed an expansion in number and diversity of B. cinerea–specific secondary metabolites relative to S. sclerotiorum. The potential diversity in secondary metabolism might be involved in adaptation to specific ecological niches. Comparative genome analysis revealed the basis of differing sexual mating compatibility systems between S. sclerotiorum and B. cinerea. The organization of the mating-type loci differs, and their structures provide evidence for the evolution of heterothallism from homothallism. These data shed light on the evolutionary and mechanistic bases of the genetically complex traits of necrotrophic pathogenicity and sexual mating. This resource should facilitate the functional studies designed to better understand what makes these fungi such successful and persistent pathogens of agronomic crops

NMDA receptor activation induces long-term potentiation of glycine synapses.

Of the fast ionotropic synapses, glycinergic synapses are the least well understood, but are vital for the maintenance of inhibitory signaling in the brain and spinal cord. Glycinergic signaling comprises half of the inhibitory signaling in the spinal cord, and glycinergic synapses are likely to regulate local nociceptive processing as well as the transmission to the brain of peripheral nociceptive information. Here we have investigated the rapid and prolonged potentiation of glycinergic synapses in the superficial dorsal horn of young male and female mice after brief activation of NMDA receptors (NMDARs). Glycinergic inhibitory postsynaptic currents (IPSCs) evoked with lamina II-III stimulation in identified GABAergic neurons in lamina II were potentiated by bath-applied Zn2+ and were depressed by the prostaglandin PGE2, consistent with the presence of both GlyRα1- and GlyRα3-containing receptors. NMDA application rapidly potentiated synaptic glycinergic currents. Whole-cell currents evoked by exogenous glycine were also readily potentiated by NMDA, indicating that the potentiation results from altered numbers or conductance of postsynaptic glycine receptors. Repetitive depolarization alone of the postsynaptic GABAergic neuron also potentiated glycinergic synapses, and intracellular EGTA prevented both NMDA-induced and depolarization-induced potentiation of glycinergic IPSCs. Optogenetic activation of trpv1 lineage afferents also triggered NMDAR-dependent potentiation of glycinergic synapses. Our results suggest that during peripheral injury or inflammation, nociceptor firing during injury is likely to potentiate glycinergic synapses on GABAergic neurons. This disinhibition mechanism may be engaged rapidly, altering dorsal horn circuitry to promote the transmission of nociceptive information to the brain

Similarities and differences of interstitial lung disease associated with pathogenic variants in SFTPC and ABCA3 in adults

International audienceAbstract Background and Objective Variants in surfactant genes SFTPC or ABCA3 are responsible for interstitial lung disease (ILD) in children and adults, with few studies in adults. Methods We conducted a multicentre retrospective study of all consecutive adult patients diagnosed with ILD associated with variants in SFTPC or ABCA3 in the French rare pulmonary diseases network, OrphaLung. Variants and chest computed tomography (CT) features were centrally reviewed. Results We included 36 patients (median age: 34 years, 20 males), 22 in the SFTPC group and 14 in the ABCA3 group. Clinical characteristics were similar between groups. Baseline median FVC was 59% ([52–72]) and DLco was 44% ([35–50]). An unclassifiable pattern of fibrosing ILD was the most frequent on chest CT, found in 85% of patients, however with a distinct phenotype with ground‐glass opacities and/or cysts. Nonspecific interstitial pneumonia and usual interstitial pneumonia were the most common histological patterns in the ABCA3 group and in the SFTPC group, respectively. Annually, FVC and DL CO declined by 1.87% and 2.43% in the SFTPC group, respectively, and by 0.72% and 0.95% in the ABCA3 group, respectively (FVC, p = 0.014 and DL CO , p = 0.004 for comparison between groups). Median time to death or lung transplantation was 10 years in the SFTPC group and was not reached at the end of follow‐up in the ABCA3 group. Conclusion SFTPC and ABCA3 ‐associated ILD present with a distinct phenotype and prognosis. A radiologic pattern of fibrosing ILD with ground‐glass opacities and/or cysts is frequently found in these rare conditions

Coronary events complicating infective endocarditis

International audienceOBJECTIVE: Acute coronary syndromes (ACS) are a rare complication of infective endocarditis (IE). Only case reports and small studies have been published to date. We report the largest series of ACS in IE. The aim of our study was to describe the incidence and mechanisms of ACS associated with IE, to assess their prognostic impact and to describe their management. METHODS: In a bicentre prospective observational cohort study, all patients with a definite diagnosis of IE were prospectively included. The incidence, mechanism and prognosis of patients with ACS were studied. RESULTS: Among 1210 consecutive patients with definite IE, 26 patients (2.2%) developed an ACS. Twenty-three patients (88%) had a coronary embolism. Two patients had coronary compression by an abscess or a pseudoaneurysm and one patient had an obstruction of his bioprosthesis and left coronary ostium by a large vegetation. Nineteen (73%) patients with ACS developed heart failure and this complication was 2.5 times more frequent than in patients without ACS (p\textless0.0001). In the ACS population, mortality rate was twice than the population without ACS. CONCLUSIONS: ACS is a rare complication of IE but is associated with an increased risk of heart failure and high mortality rate

Phenotypic characterization of interstitial lung disease associated with mutations inSFTPC and ABCA3 in adults

International audienceIntroduction: Mutations in surfactant genes SFTPC or ABCA3 are responsible for interstitial lung disease (ILD) in children and adults. Despite numerous paediatric data, few studies described these entities in adults.Methods: We conducted a multicenter retrospective study of adult patients with ILD associated with mutations in SFTPC or ABCA3 in the French rare pulmonary diseases network OrphaLung.Results: We included 36 patients, 22 in the SFTPC group and 14 in the ABCA3 group. Clinical characteristics were similar between the two groups. Baseline pulmonary function tests reported a median FVC of 59% ([52 – 72]%), a median FEV1 of 63% ([48,3 – 73,3] %), a median TLC of 65 % ([59 – 76] %) and a median DLco of 44 % ([35,4 – 50] %). A pattern of unclassifiable fibrosing ILD was the most frequent on chest computed tomography, found in 85% of patients. Nonspecific interstitial pneumonia and usual interstitial pneumonia were the most common histological patterns in the ABCA3 group and in the SFTPC group, respectively. Median survival before death or lung transplantation was 10 years in the SFTPC group (4 deaths and 8 patients with lung transplantation) and was not reached at the end of follow-up in the ABCA3 group (1 death and 2 patients with lung transplantation).Conclusion: Patients with ILD and mutations in SFTPC or ABCA3 present a distinct phenotype of unclassifiable fibrosing ILD with cysts and ground glass opacities, and their prognosis is often severe. While our results highlight the phenotypical heterogeneity of these patients, they also expand our knowledge of these rare causes of ILD in adult

Phenotypic characterization of interstitial lung disease associated with mutations inSFTPC and ABCA3 in adults

International audienceIntroduction: Mutations in surfactant genes SFTPC or ABCA3 are responsible for interstitial lung disease (ILD) in children and adults. Despite numerous paediatric data, few studies described these entities in adults.Methods: We conducted a multicenter retrospective study of adult patients with ILD associated with mutations in SFTPC or ABCA3 in the French rare pulmonary diseases network OrphaLung.Results: We included 36 patients, 22 in the SFTPC group and 14 in the ABCA3 group. Clinical characteristics were similar between the two groups. Baseline pulmonary function tests reported a median FVC of 59% ([52 – 72]%), a median FEV1 of 63% ([48,3 – 73,3] %), a median TLC of 65 % ([59 – 76] %) and a median DLco of 44 % ([35,4 – 50] %). A pattern of unclassifiable fibrosing ILD was the most frequent on chest computed tomography, found in 85% of patients. Nonspecific interstitial pneumonia and usual interstitial pneumonia were the most common histological patterns in the ABCA3 group and in the SFTPC group, respectively. Median survival before death or lung transplantation was 10 years in the SFTPC group (4 deaths and 8 patients with lung transplantation) and was not reached at the end of follow-up in the ABCA3 group (1 death and 2 patients with lung transplantation).Conclusion: Patients with ILD and mutations in SFTPC or ABCA3 present a distinct phenotype of unclassifiable fibrosing ILD with cysts and ground glass opacities, and their prognosis is often severe. While our results highlight the phenotypical heterogeneity of these patients, they also expand our knowledge of these rare causes of ILD in adult

Phenotypic characterization of interstitial lung disease associated with mutations inSFTPC and ABCA3 in adults

International audienceIntroduction: Mutations in surfactant genes SFTPC or ABCA3 are responsible for interstitial lung disease (ILD) in children and adults. Despite numerous paediatric data, few studies described these entities in adults.Methods: We conducted a multicenter retrospective study of adult patients with ILD associated with mutations in SFTPC or ABCA3 in the French rare pulmonary diseases network OrphaLung.Results: We included 36 patients, 22 in the SFTPC group and 14 in the ABCA3 group. Clinical characteristics were similar between the two groups. Baseline pulmonary function tests reported a median FVC of 59% ([52 – 72]%), a median FEV1 of 63% ([48,3 – 73,3] %), a median TLC of 65 % ([59 – 76] %) and a median DLco of 44 % ([35,4 – 50] %). A pattern of unclassifiable fibrosing ILD was the most frequent on chest computed tomography, found in 85% of patients. Nonspecific interstitial pneumonia and usual interstitial pneumonia were the most common histological patterns in the ABCA3 group and in the SFTPC group, respectively. Median survival before death or lung transplantation was 10 years in the SFTPC group (4 deaths and 8 patients with lung transplantation) and was not reached at the end of follow-up in the ABCA3 group (1 death and 2 patients with lung transplantation).Conclusion: Patients with ILD and mutations in SFTPC or ABCA3 present a distinct phenotype of unclassifiable fibrosing ILD with cysts and ground glass opacities, and their prognosis is often severe. While our results highlight the phenotypical heterogeneity of these patients, they also expand our knowledge of these rare causes of ILD in adult

Phenotypic characterization of interstitial lung disease associated with mutations inSFTPC and ABCA3 in adults

International audienceIntroduction: Mutations in surfactant genes SFTPC or ABCA3 are responsible for interstitial lung disease (ILD) in children and adults. Despite numerous paediatric data, few studies described these entities in adults.Methods: We conducted a multicenter retrospective study of adult patients with ILD associated with mutations in SFTPC or ABCA3 in the French rare pulmonary diseases network OrphaLung.Results: We included 36 patients, 22 in the SFTPC group and 14 in the ABCA3 group. Clinical characteristics were similar between the two groups. Baseline pulmonary function tests reported a median FVC of 59% ([52 – 72]%), a median FEV1 of 63% ([48,3 – 73,3] %), a median TLC of 65 % ([59 – 76] %) and a median DLco of 44 % ([35,4 – 50] %). A pattern of unclassifiable fibrosing ILD was the most frequent on chest computed tomography, found in 85% of patients. Nonspecific interstitial pneumonia and usual interstitial pneumonia were the most common histological patterns in the ABCA3 group and in the SFTPC group, respectively. Median survival before death or lung transplantation was 10 years in the SFTPC group (4 deaths and 8 patients with lung transplantation) and was not reached at the end of follow-up in the ABCA3 group (1 death and 2 patients with lung transplantation).Conclusion: Patients with ILD and mutations in SFTPC or ABCA3 present a distinct phenotype of unclassifiable fibrosing ILD with cysts and ground glass opacities, and their prognosis is often severe. While our results highlight the phenotypical heterogeneity of these patients, they also expand our knowledge of these rare causes of ILD in adult