Cross-species analysis of viral nucleic acid interacting proteins identifies TAOKs as innate immune regulators

The cell intrinsic antiviral response of multicellular organisms developed over millions of years and critically relies on the ability to sense and eliminate viral nucleic acids. Here we use an affinity proteomics approach in evolutionary distant species (human, mouse and fly) to identify proteins that are conserved in their ability to associate with diverse viral nucleic acids. This approach shows a core of orthologous proteins targeting viral genetic material and species-specific interactions. Functional characterization of the influence of 181 candidates on replication of 6 distinct viruses in human cells and flies identifies 128 nucleic acid binding proteins with an impact on virus growth. We identify the family of TAO kinases (TAOK1, -2 and -3) as dsRNA-interacting antiviral proteins and show their requirement for type-I interferon induction. Depletion of TAO kinases in mammals or flies leads to an impaired response to virus infection characterized by a reduced induction of interferon stimulated genes in mammals and impaired expression of srg1 and diedel in flies. Overall, our study shows a larger set of proteins able to mediate the interaction between viral genetic material and host factors than anticipated so far, attesting to the ancestral roots of innate immunity and to the lineage-specific pressures exerted by viruses. Whether there are conserved nucleic acid (NA) binding proteins across species is not fully known. Using data from human, mouse and fly, the authors identify common binders, implicate TAOKs and show that these kinases bind NAs across species and promote virus defence in mammalian cells.We further thank Korbinian Mayr, Igor Paron, and Gaby Sowa for maintaining mass spectrometers and the MPI-B core facility, especially Judith Scholz, Leopold Urich, Sabine Suppmann, and Stephan Uebel, for support..

Les progrès du 5e objectif du millénaire pour le développement, globalement et les exemples d'application au Maghreb: quoi de neuf?

The first part of this article examines the global progress towards target A of the fifth Millennium Development Goal (MDG5). The target is to reduce by three quarters the maternal mortality ratio between 1990 and 2015. This implies that most maternal deaths could be avoided. Recent sources are examined and the MMEIG data set is used for the comparison as being the one in use by the United Nations. Giving birth remains a risk process, particularly in Souhern Asia and sub-Saharan. In the second part data from Algeria, Lybia, Mauritania, Morocco and Tunisia, the five countries composing the Maghreb are examined. Four of these countries are in good progress and possibly on track. In Morocco a full process has been developed including emproved governance, accessibility and quality. This has included a full procedure of confidential enquiry into maternal health, including the five recommended steps of the process: enhanced identification, documentation, determination of causes, assessment of substandard care and recommendations based on the results of the four first steps. Maternal haemorrhage is the leading cause of death in that region. © 2012 Springer-Verlag France.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Chemoenzymatic total synthesis of sorbicatechol structural analogues and evaluation of their antiviral potential.

Sorbicillinoids are fungal polyketides characterized by highly complex and diverse molecular structures, with considerable stereochemical intricacy combined with a high degree of oxygenation. Many sorbicillinoids possess promising biological activities. An interesting member of this natural product family is sorbicatecholA, which is reported to have antiviral activity, particularly against influenzaA virus (H1N1). Through a straightforward, one-pot chemoenzymatic approach with recently developed oxidoreductase SorbC, the characteristic bicyclo[2.2.2]octane core of sorbicatechol is structurally diversified by variation of its natural 2-methoxyphenol substituent. This facilitates the preparation of a focused library of structural analogues bearing substituted aromatic systems, alkanes, heterocycles, and ethers. Fast access to this structural diversity provides an opportunity to explore the antiviral potential of the sorbicatechol family

J Fr Ophtalmol

International audienc

Which visual acuity measurements define high-quality care for patients with neovascular age-related macular degeneration treated with ranibizumab?

PURPOSE: The purpose of this study is to define which visual acuity (VA) measurements are the best indicators of high-quality care for patients receiving intravitreal ranibizumab for neovascular age-related macular degeneration (nAMD). METHODS: Analysis of prospectively collected data recorded within an electronic medical record system on treatment-naive, first-eligible eyes with nAMD, treated with ranibizumab using an as-needed treatment regimen with a minimum follow-up of 1 year. Data collection included the following: age, gender, laterality, type of nAMD, VA, central 1 mm OCT retinal thickness, number of intravitreal injections, and number of follow-up assessments. RESULTS: Data were available on the first-treated eye from 406 patients with at least 1 year follow-up; of these, 198 had data at 2 years. The mean baseline VA of 54.4 Early Treatment Diabetic Retinopathy Study letters improved to 58.5 letters at 12 months and to 56.8 letters at 24 months. The mean VA changes from baseline to 1 year were +6.5, +7.5, +1.7, and −1.5 letters, respectively, for baseline VA categories of 23–35, 36–55, 56–70, and >70 letters. Change in mean VA from the end of the loading phase to year 1 ranged from −2.9 to +1.4 letters for the different baseline VA categories. The mean number of injections were similar across baseline VA categories ranging from 5.7 to 6.0 injections in year 1 and from 3.3 to 3.8 in year 2. CONCLUSIONS: This large, real-world series demonstrates that mean change in VA is largely a function of selection criteria and baseline VA. The quality of a service is therefore better judged by actual VA outcomes and maintenance of vision after the loading phase

A systematic review to assess the “Treat-and-Extend” dosing regimen for neovascular age-related macular degeneration using ranibizumab

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the developed world. Monthly or as-needed (PRN) dosing strategies of intravitreal ranibizumab have been established as efficacious treatment options for neovascular AMD. More recently, the ‘treat-and-extend’ dosing regimen (TREX) is being adopted in clinical practice as it represents a patient-centric and economical option, reducing treatment burden by extending injection intervals when possible. However, the efficacy of TREX using ranibizumab monotherapy remains to be defined. Therefore, we performed a systematic review to assess the current evidence for TREX using ranibizumab by searching MEDLINE, Embase and PubMed. Of the 1733 articles identified, nine TREX studies were included in our analysis (n=748 eyes). Average patient age was 79.25 (range: 77.34–82.00; SD: 7.27). Baseline BCVA ranged from 48.5–68.9 ETDRS letters. BCVA improvement was 8.92 letters at 1 year (range: 6.5–11.5; SD: 7.54), as a weighted mean accounting for numbers of study eyes. The weighted mean number of injections at one year was 8.60 (range: 7.3–12.0; SD: 1.73). Previously, the landmark ANCHOR and MARINA trials reported gains of 11.3 and 7.2 letters, respectively, using monthly ranibizumab. Chin-Yee et al reported a gain of 3.5 ETDRS letters with 5.3 (S.D. 0.66) PRN ranibizumab injections as weighted means at 1 year in their recent systematic review. Our analysis suggests that TREX delivers visual outcomes superior to PRN and approaches similar efficacy to monthly injections. Further RCTs are needed to fully evaluate the efficacy and economy of TREX in the long-term