Repression of Floral Meristem Fate Is Crucial in Shaping Tomato Inflorescence

Tomato is an important crop and hence there is a great interest in understanding the genetic basis of its flowering. Several genes have been identified by mutations and we constructed a set of novel double mutants to understand how these genes interact to shape the inflorescence. It was previously suggested that the branching of the tomato inflorescence depends on the gradual transition from inflorescence meristem (IM) to flower meristem (FM): the extension of this time window allows IM to branch, as seen in the compound inflorescence (s) and falsiflora (fa) mutants that are impaired in FM maturation. We report here that JOINTLESS (J), which encodes a MADS-box protein of the same clade than SHORT VEGETATIVE PHASE (SVP) and AGAMOUS LIKE 24 (AGL24) in Arabidopsis, interferes with this timing and delays FM maturation, therefore promoting IM fate. This was inferred from the fact that j mutation suppresses the high branching inflorescence phenotype of s and fa mutants and was further supported by the expression pattern of J, which is expressed more strongly in IM than in FM. Most interestingly, FA - the orthologue of the Arabidopsis LEAFY (LFY) gene - shows the complementary expression pattern and is more active in FM than in IM. Loss of J function causes premature termination of flower formation in the inflorescence and its reversion to a vegetative program. This phenotype is enhanced in the absence of systemic florigenic protein, encoded by the SINGLE FLOWER TRUSS (SFT) gene, the tomato orthologue of FLOWERING LOCUS T (FT). These results suggest that the formation of an inflorescence in tomato requires the interaction of J and a target of SFT in the meristem, for repressing FA activity and FM fate in the IM

Coxiella burnetti prosthetic joint infection in an immunocompromised woman: iterative surgeries, prolonged ofloxacin-rifampin treatment and complex reconstruction were needed for the cure

International audienceAbstract Background Q fever is a zoonotic disease caused by the bacterium Coxiella burnetii , a strictly intracellular pathogen that can cause acute and chronic infection. Chronic Q fever can occur in immunocompetent as well as in immuno-compromised hosts, as a persistent localized infection. The main localizations are endocardial, vascular and, less frequently, osteoarticular. The most frequent osteoarticular form is spondyliscitis. Recommended treatment is combined doxycycline and hydroxychloroquine for 18 months, with cotrimoxazole as another option. Coxiella burnetti infection has been implicated in rare cases of prosthetic joint infection (PJI), and the medical and surgical management and outcome in such cases have been little reported. Case presentation We report an unusual case of chronic Q fever involving a hip arthroplasty in an immunocompromised woman treated with tumor necrosis factor (TNF)-α blockers for rheumatoid arthritis. Numerous surgical procedures (explantation, “second look”, femoral resection and revision by megaprosthesis), modification of the immunosuppressant therapy and switch from doxycycline-hydroxychloroquine to prolonged ofloxacin-rifampin combination therapy were needed to achieve reconstruction and treat the PJI, with a follow-up of 7 years. Conclusions Coxiella burnetti PJI is a complex infection that requires dedicated management in an experienced reference center. Combined use of ofloxacin-rifampin can be effective

Necrotizing external otitis: analysis of relapse risk factors in 66 patients managed during a 12 year period

International audienceAbstract Background Necrotizing external otitis (NEO) is a severe infection of the skull base that occurs generally in the elderly and/or in diabetic recipients. There are few data in the literature about the therapeutic management of this complex bone infection. Objectives To analyse relapses after NEO treatment completion, and to describe the clinical features of NEO. Methods We performed a retrospective cohort study in the Lyon regional reference centre for the management of complex bone and joint infections. Consecutive cases of NEO from 1 January 2006 to 31 December 2018 were included. The primary outcome was the relapse of NEO. Variables were analysed using Cox regression survival analysis with adjusted hazard ratio (aHR) and Kaplan–Meier curve. Results Sixty-six patients were included. Median age was 75 (IQR 69–81) years and 46 (70%) patients were diabetic. Eleven patients (17%) had temporomandibular arthritis, 10 (15%) cranial nerve paralysis, 2 (3%) cerebral thrombophlebitis, and 2 (3%) contiguous abscess. Microbiological documentation was obtained in 56 patients and revealed Pseudomonas aeruginosa in 44/56 patients (79%). Nine (14%) cases had no microbiological documentation. Antibiotic therapy was dual for 63 (95%) patients. During a median follow-up of 27 (IQR 12–40) months, 16 out of 63 (25%) patients experienced a relapse. Fungal infection was significantly associated with relapse [aHR 4.1 (95% CI 1.1–15); P = 0.03]. Conclusions NEO is a severe bone infection, mainly (but not exclusively) caused by P. aeruginosa, which occurs in elderly and diabetic recipients. Fungal infections at baseline significantly impact the outcome

Comprehensive genomic characterization of head and neck squamous cell carcinomas

The Cancer Genome Atlas profiled 279 head and neck squamous cell carcinomas (HNSCCs) to provide a comprehensive landscape of somatic genomic alterations. Here we show that human-papillomavirus-associated tumours are dominated by helical domain mutations of the oncogene PIK3CA, novel alterations involving loss of TRAF3, and amplification of the cell cycle gene E2F1. Smoking-related HNSCCs demonstrate near universal loss-of-function TP53 mutations and CDKN2A inactivation with frequent copy number alterations including amplification of 3q26/28 and 11q13/22. A subgroup of oral cavity tumours with favourable clinical outcomes displayed infrequent copy number alterations in conjunction with activating mutations of HRAS or PIK3CA, coupled with inactivating mutations of CASP8, NOTCH1 and TP53. Other distinct subgroups contained loss-of-function alterations of the chromatin modifier NSD1, WNT pathway genes AJUBA and FAT1, and activation of oxidative stress factor NFE2L2, mainly in laryngeal tumours. Therapeutic candidate alterations were identified in most HNSCCsclose9

The Molecular Taxonomy of Primary Prostate Cancer

There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defectsclose