Associative learning in the cnidarian Nematostella vectensis.

The ability to learn and form memories allows animals to adapt their behavior based on previous experiences. Associative learning, the process through which organisms learn about the relationship between two distinct events, has been extensively studied in various animal taxa. However, the existence of associative learning, prior to the emergence of centralized nervous systems in bilaterian animals, remains unclear. Cnidarians such as sea anemones or jellyfish possess a nerve net, which lacks centralization. As the sister group to bilaterians, they are particularly well suited for studying the evolution of nervous system functions. Here, we probe the capacity of the starlet sea anemone Nematostella vectensis to form associative memories by using a classical conditioning approach. We developed a protocol combining light as the conditioned stimulus with an electric shock as the aversive unconditioned stimulus. After repetitive training, animals exhibited a conditioned response to light alone indicating that they learned the association. In contrast, all control conditions did not form associative memories. Besides shedding light on an aspect of cnidarian behavior, these results root associative learning before the emergence of NS centralization in the metazoan lineage and raise fundamental questions about the origin and evolution of cognition in brainless animals

Beyond the classical type I error: Bayesian metrics for Bayesian designs using informative priors

There is growing interest in Bayesian clinical trial designs with informative prior distributions, e.g. for extrapolation of adult data to pediatrics, or use of external controls. While the classical type I error is commonly used to evaluate such designs, it cannot be strictly controlled and it is acknowledged that other metrics may be more appropriate. We focus on two common situations - borrowing control data or information on the treatment contrast - and discuss several fully probabilistic metrics to evaluate the risk of false positive conclusions. Each metric requires specification of a design prior, which can differ from the analysis prior and permits understanding of the behaviour of a Bayesian design under scenarios where the analysis prior differs from the true data generation process. The metrics include the average type I error and the pre-posterior probability of a false positive result. We show that, when borrowing control data, the average type I error is asymptotically (in certain cases strictly) controlled when the analysis and design prior coincide. We illustrate use of these Bayesian metrics with real applications, and discuss how they could facilitate discussions between sponsors, regulators and other stakeholders about the appropriateness of Bayesian borrowing designs for pivotal studies

A subset of dendritic cells as a major and constitutive source of IL-22BP

Poster presentationInternational audienc

TNF-block genotypes influence susceptibility to HIV-associated sensory neuropathy in Indonesians and South Africans

HIV-associated sensory neuropathy (HIV-SN) is a disabling complication of HIV disease and antiretroviral therapies (ART). Since stavudine was removed from recommended treatment schedules, the prevalence of HIV-SN has declined and associated risk factors have changed. With stavudine, rs1799964*C (TNF-1031) associated with HIV-SN in Caucasians and Indonesians but not in South Africans. Here, we investigate associations between HIV-SN and rs1799964*C and 12 other polymorphisms spanning TNF and seven neighboring genes (the TNF-block) in Indonesians (n = 202; 34/168 cases) and South Africans (n = 75; 29/75 cases) treated without stavudine. Haplotypes were derived using fastPHASE and haplotype networks built with PopART. There were no associations with rs1799964*C in either population. However, rs9281523*C in intron 10 of BAT1 (alternatively DDX39B) independently associated with HIV-SN in Indonesians after correcting for lower CD4 T-cell counts and \u3e500 copies of HIV RNA/mL (model p = 0.0011, Pseudo R2 = 0.09). rs4947324*T (between NFKBIL1 and LTA) independently associated with reduced risk of HIV-SN and shared haplotype 1 (containing no minor alleles) associated with increased risk of HIV-SN after correcting for greater body weight, a history of tuberculosis and nadir CD4 T-cell counts (model: p = 0.0003, Pseudo R2 = 0.22). These results confirm TNF-block genotypes influence susceptibility of HIV-SN. However, critical genotypes differ between ethnicities and with stavudine use

Rapid detection and subtyping of European swine influenza viruses in porcine clinical samples by haemagglutinin- and neuraminidase-specific tetra- and triplex real-time RT-PCRs

BACKGROUND: A diversifying pool of mammalian‐adapted influenza A viruses (IAV) with largely unknown zoonotic potential is maintained in domestic swine populations worldwide. The most recent human influenza pandemic in 2009 was caused by a virus with genes originating from IAV isolated from swine. Swine influenza viruses (SIV) are widespread in European domestic pig populations and evolve dynamically. Knowledge regarding occurrence, spread and evolution of potentially zoonotic SIV in Europe is poorly understood. OBJECTIVES: Efficient SIV surveillance programmes depend on sensitive and specific diagnostic methods which allow for cost‐effective large‐scale analysis. METHODS: New SIV haemagglutinin (HA) and neuraminidase (NA) subtype‐ and lineage‐specific multiplex real‐time RT‐PCRs (RT‐qPCR) have been developed and validated with reference virus isolates and clinical samples. RESULTS: A diagnostic algorithm is proposed for the combined detection in clinical samples and subtyping of SIV strains currently circulating in Europe that is based on a generic, M‐gene‐specific influenza A virus RT‐qPCR. In a second step, positive samples are examined by tetraplex HA‐ and triplex NA‐specific RT‐qPCRs to differentiate the porcine subtypes H1, H3, N1 and N2. Within the HA subtype H1, lineages “av” (European avian‐derived), “hu” (European human‐derived) and “pdm” (human pandemic A/H1N1, 2009) are distinguished by RT‐qPCRs, and within the NA subtype N1, lineage “pdm” is differentiated. An RT‐PCR amplicon Sanger sequencing method of small fragments of the HA and NA genes is also proposed to safeguard against failure of multiplex RT‐qPCR subtyping. CONCLUSIONS: These new multiplex RT‐qPCR assays provide adequate tools for sustained SIV monitoring programmes in Europe

R.E.D. Server: a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments

R.E.D. Server is a unique, open web service, designed to derive non-polarizable RESP and ESP charges and to build force field libraries for new molecules/molecular fragments. It provides to computational biologists the means to derive rigorously molecular electrostatic potential-based charges embedded in force field libraries that are ready to be used in force field development, charge validation and molecular dynamics simulations. R.E.D. Server interfaces quantum mechanics programs, the RESP program and the latest version of the R.E.D. tools. A two step approach has been developed. The first one consists of preparing P2N file(s) to rigorously define key elements such as atom names, topology and chemical equivalencing needed when building a force field library. Then, P2N files are used to derive RESP or ESP charges embedded in force field libraries in the Tripos mol2 format. In complex cases an entire set of force field libraries or force field topology database is generated. Other features developed in R.E.D. Server include help services, a demonstration, tutorials, frequently asked questions, Jmol-based tools useful to construct PDB input files and parse R.E.D. Server outputs as well as a graphical queuing system allowing any user to check the status of R.E.D. Server jobs

Antiviral Activities of Sulfated Polysaccharides Isolated from Sphaerococcus coronopifolius (Rhodophytha, Gigartinales) and Boergeseniella thuyoides (Rhodophyta, Ceramiales)

Water-soluble sulfated polysaccharides isolated from two red algae Sphaerococcus coronopifolius (Gigartinales, Sphaerococcaceae) and Boergeseniella thuyoides (Ceramiales, Rhodomelaceae) collected on the coast of Morocco inhibited in vitro replication of the Human Immunodeficiency Virus (HIV) at 12.5 μg/mL. In addition, polysaccharides were capable of inhibiting the in vitro replication of Herpes simplex virus type 1 (HSV-1) on Vero cells values of EC50 of 4.1 and 17.2 μg/mL, respectively. The adsorption step of HSV-1 to the host cell seems to be the specific target for polysaccharide action. While for HIV-1, these results suggest a direct inhibitory effect on HIV-1 replication by controlling the appearance of the new generations of virus and potential virucidal effect. The polysaccharides from S. coronopifolius (PSC) and B. thuyoides (PBT) were composed of galactose, 3,6-anhydrogalactose, uronics acids, sulfate in ratios of 33.1, 11.0, 7.7 and 24.0% (w/w) and 25.4, 16.0, 3.2, 7.6% (w/w), respectively

Tracker Operation and Performance at the Magnet Test and Cosmic Challenge

During summer 2006 a fraction of the CMS silicon strip tracker was operated in a comprehensive slice test called the Magnet Test and Cosmic Challenge (MTCC). At the MTCC, cosmic rays detected in the muon chambers were used to trigger the readout of all CMS sub-detectors in the general data acquisition system and in the presence of the 4 T magnetic field produced by the CMS superconducting solenoid. This document describes the operation of the Tracker hardware and software prior, during and after data taking. The performance of the detector as resulting from the MTCC data analysis is also presented

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio