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PARN, poly(A)-specific ribonuclease, regulates the turnover of mRNAs and the maturation and stabilization of the hTR RNA component of telomerase. Biallelic PARN mutations were associated with Hoyeraal-Hreidarsson (HH) syndrome, a rare telomere biology disorder that, because of its severity, is likely not exclusively due to hTR down-regulation. Whether PARN deficiency was affecting the expression of telomere-related genes was still unclear. Using cells from two unrelated HH individuals carrying novel PARN mutations and a human PARN knock-out (KO) cell line with inducible PARN complementation, we found that PARN deficiency affects both telomere length and stability and down-regulates the expression of TRF1, TRF2, TPP1, RAP1, and POT1 shelterin transcripts. Down-regulation of dyskerin-encoding DKC1 mRNA was also observed and found to result from p53 activation in PARN-deficient cells. We further showed that PARN deficiency compromises ribosomal RNA biogenesis in patients' fibroblasts and cells from heterozygous Parn KO mice. Homozygous Parn KO however resulted in early embryonic lethality that was not overcome by p53 KO. Our results refine our knowledge on the pleiotropic cellular consequences of PARN deficiency. C1 [Benyelles, Maname; Kermasson, Laetitia; de Villartay, Jean-Pierre; Revy, Patrick] INSERM, UMR 1163, Lab Genome Dynam Immune Syst, Paris, France. [Benyelles, Maname; Kermasson, Laetitia; de Villartay, Jean-Pierre; Revy, Patrick] Paris Descartes Sorbonne Paris Cite Univ, Imagine Inst, Lab Labellise Ligue, Paris, France. [Episkopou, Harikleia; Poulain, Florian; Decottignies, Anabelle] Catholic Univ Louvain, de Duve Inst, Brussels, Belgium. [O'Donohue, Marie-Francoise; Gleizes, Pierre-Emmanuel] Univ Toulouse, Lab Biol Mol Eucaryote, CBI, CNRS,UPS, Toulouse, France. [Frange, Pierre] Univ Paris 05, Sorbonne Paris Cite, EA 7327, Paris, France. [Frange, Pierre] Hop Necker Enfants Malad, AP HP, Lab Microbiol Clin, Paris, France. [Frange, Pierre] Hop Necker Enfants Malad, AP HP, Unite Immunol Hematol & Rhumatol Pediat, Paris, France. [Belen, Fatma Burcu] Baskent Univ, Pediat Hematol, Fac Med, Ankara, Turkey. [Polat, Meltem] Pamukkale Univ, Pediat Infect Dis, Fac Med, Dept Pediat Infect Dis, Denizli, Turkey. [Bole-Feysot, Christine] Paris Descartes Sorbonne Paris Cite Univ, Imagine Inst, Genom Platform, INSERM,UMR 1163, Paris, France. [Bole-Feysot, Christine] INSERM U1163, Imagine Inst Struct Federat Rech Necker, Genom Core Facil, Paris, France. [Langa-Vives, Francina] Inst Pasteur, Ctr Ingn Genet Murine, Paris, France. [Callebaut, Isabelle] Sorbonne Univ, IMPMC, UMR CNRS 7590, Museum Natl Hist Nat, Paris, France.

Recently, a novel process of microbially mediated sulfide oxidation has been discovered [1]. In this process, named electrogenic sulfur oxidation (e-SOx), long filamentous cable bacteria couple the reduction of oxygen near the sediment-water interface to the oxidation of free sulfide and iron sulfides in deeper sediment layers via electrical currents that run over centimetre-wide distances [1,2]. This spatial decoupling of redox reactions generates a distinct pH profile with an alkaline peak just below the sediment water interface and an acidic pH minimum in the deeper sediment layers. These strong alkalinity gradients have been shown to significantly influence the elemental cycling of iron, manganese and carbonate minerals in the upper ~5 cm of the seafloor through the acidic dissolution of pH-sensitive minerals such as iron sulfides and carbonates [3,4]. Metal oxides and sulfide minerals are primary drivers for trace metals cycling [3,5] and thus, e-SOx will likely affect trace metal cycling. Yet, the impact of e-SOx on trace metal cycling is still largely unknown Here we present results from in situ sampling (November 2014), and laboratory sediment incubations from the Belgian Coastal Zone (BCZ, Station 130). By combining the results of the microsensor profiling, pore water analysis and sequential solid phase extractions for trace metals and inorganic sulfur, it is shown that e-SOx is the primary driver of the biogeochemical cycles of cobalt and arsenic in the BCZ. Trace metal cycling is driven by the dissolution of sulfide minerals at depth and the reprecipitation of iron and manganese oxides near the sediment-water interface.

The first European Rhinology Research Forum organized by the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) was held in the Royal Academy of Medicine in Brussels on 17th and 18th November 2016, in collaboration with the European Rhinologic Society (ERS) and the Global Allergy and Asthma European Network (GA2LEN). One hundred and thirty participants (medical doctors from different specialties, researchers, as well as patients and industry representatives) from 27 countries took part in the multiple perspective discussions including brainstorming sessions on care pathways and research needs in rhinitis and rhinosinusitis. The debates started with an overview of the current state of the art, including weaknesses and strengths of the current practices, followed by the identification of essential research needs, thoroughly integrated in the context of Precision Medicine (PM), with personalized care, prediction of success of treatment, participation of the patient and prevention of disease as key principles for improving current clinical practices. This report provides a concise summary of the outcomes of the brainstorming sessions of the European Rhinology Research Forum 2016.

The first European Rhinology Research Forum organized by the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) was held in the Royal Academy of Medicine in Brussels on 17th and 18th November 2016, in collaboration with the European Rhinologic Society (ERS) and the Global Allergy and Asthma European Network (GA2LEN). One hundred and thirty participants (medical doctors from different specialties, researchers, as well as patients and industry representatives) from 27 countries took part in the multiple perspective discussions including brainstorming sessions on care pathways and research needs in rhinitis and rhinosinusitis. The debates started with an overview of the current state of the art, including weaknesses and strengths of the current practices, followed by the identification of essential research needs, thoroughly integrated in the context of Precision Medicine (PM), with personalized care, prediction of success of treatment, participation of the patient and prevention of disease as key principles for improving current clinical practices. This report provides a concise summary of the outcomes of the brainstorming sessions of the European Rhinology Research Forum 2016.

Conjunctival allergen provocation test (CAPT) reproduces the events occurring by instilling an allergen on the ocular surface. This paper is the compilation of a task force focussed on practical aspects of this technique based on the analysis of 131 papers. Main mechanisms involved are reviewed. Indications are diagnosing the allergen(s)-triggering symptoms in IgE-mediated ocular allergy in seasonal, acute or perennial forms of allergic conjunctivitis, especially when the relevance of the allergen is not obvious or in polysensitized patients. Contraindications are limited to ongoing systemic severe pathology, asthma and eye diseases. CAPT should be delayed if receiving systemic steroids or antihistamines. Local treatment should be interrupted according to the half-life of each drug. Prerequisites are as follows: obtaining informed consent; evidencing of an allergen by skin prick tests and/or serum-specific IgE dosages; being able to deal with an unlikely event such as acute asthma exacerbation, urticaria or anaphylaxis, or an exacerbation of allergic conjunctivitis. Allergen extracts should be diluted locally prior to administration. Positive criteria are based on itching or quoted according to a composite score. An alternative scoring is based on itching. CAPT remains underused in daily practice, although it is a safe and simple procedure which can provide valuable clinical information.