Transcription of histones H1 and H2B is regulated by several immune stimuli in gilthead seabream and European sea bass

Histones (H1 to H4) are the primary proteins which mediate the folding of DNA into chromatin; however, and in addition to this function, histones have been also related to antimicrobial peptides (AMPs) activity in vertebrates, in fact, mammalian H1 is mobilized as part as the anti-viral immune response. In fish, histones with AMP activity have been isolated and characterized mainly from skin and gonads. One of most threatening pathogens for wild and cultured fish species nowadays is nodavirus (NNV), which target tissues are the brain and retina, but it is also able to colonize the gonad and display vertical transmission. Taking all this into account we have identified the h1 and h2b coding sequences in Eu- ropean sea bass (Dicentrarchus labrax) and gilthead seabream (Sparus aurata) fish species and studied their pattern of expression under naïve conditions and NNV in vivo infection. The data obtained prompted us to study their role on the immune response of gonad and head-kidney leucocytes upon viral (NNV), bacteria (Vibrio anguillarumor Photobacteriumdamselae), pathogen-associated molecular patterns (PAMPs) or mitogens stimulation. The h1 and h2b genes are expressed in a wide range of tissues and their expression is modify by infection or other immune stimuli, but further studies will be needed to determine the significance of these changes. These results suggest that h1 expression is related to the immune response against NNV in the brain, while h2b transcription seems to be more important in the head-kidney. Moreover, the potential role of histones as anti-viral agents is suggested and further characterization is in progress

ANAIS: Status and prospects

AbstractANAIS (Annual modulation with NAI Scintillators) experiment aims to look for dark matter annual modulation with 250 kg of ultra-pure NaI(Tl) scintillators at the Canfranc Underground Laboratory (LSC), in order to confirm the DAMA/LIBRA positive signal in a model-independent way. The detector will consists in an array of close-packed single modules, each of them coupled to two high efficiency Hamamatsu photomultipliers. Two 12.5 kg each NaI(Tl) crystals provided by Alpha Spectra are currently taking data at the LSC. These modules have shown an outstanding light collection efficiency (12-16 phe/keV), about the double of that from DAMA/LIBRA phase 1 detectors, which could enable reducing the energy threshold down to 1 keVee. ANAIS crystal radiopurity goals are fulfilled for 232Th and 238U chains, assuming equilibrium, and in the case of 40K, present crystals activity (although not at the required 20 ppb level) could be acceptable. However, a 210Pb contamination out-of-equilibrium has been identified and its origin traced back, so we expect it will be avoided in next prototypes. Finally, current status and prospects of the experiment considering several exposure and background scenarios are presented

Vaccination with UV-inactivated nodavirus partly protects European sea bass against infection, while inducing few changes in immunity

Developing viral vaccines through the ultraviolet (UV) inactivation of virus is promising technique since it is straightforward and economically affordable, while the resulting viruses are capable of eliciting an adequate antiviral immune response. Nodavirus (NNV) is a devastating virus that mainly affects European sea bass juveniles and larvae, causing serious economic losses in Mediterranean aquaculture. In this work, a potential vaccine consisting on UV-inactivated NNV (iNNV) was generated and administered to healthy juveniles of European sea bass to elucidate whether it triggers the immune response and improves their survival upon challenge. First, iNNV failed to replicate in cell cultures and its intraperitoneal administration to sea bass juveniles also failed to produce fish mortality and induction of the type I interferon (IFN) pathway, indicating that the NNV was efficiently inactivated. By contrast, iNNV administration induced significant serum non-specific antimicrobial activity as well as a specific antiviral activity and immunoglobulin M (IgM) titres against NNV. Interestingly, few changes were observed at transcriptional level in genes related to either innate or adaptive immunity, suggesting that iNNV could be modulating the immune response at protein or functional level. In addition, the iNNV vaccinated group showed improved survival, reaching a relative survival percentage of 57.9%. Moreover, challenged fish that had been vaccinated presented increased serum antibacterial, antiviral and IgM titres, as well as the higher transcription of mhc1a, ifn, isg15 and cd8a genes in brain, while in the head-kidney the transcription of mhc1a, mhc2b and cd8a was down regulated and mx, isg15 and tcrb was up-regulated. Although the UV-inactivated vaccine against NNV showed promising results, more effort should be addressed to improving this prophylactic method by increasing our understanding of its action mechanisms, thus enabling the mortality rate of NNV to be further reduced.Postprint3,26

Potential Impacts in the Gilthead Seabream Larviculture by Nodavirus

The nervous necrosis virus (NNV) leads to viral encephalopathy and retinopathy (VER) disease in more than 170 fish species, mainly from marine habitats. It replicates in the central nervous tissues, reaching up to 100% mortalities after a few days of infection, mainly in the larvae and juvenile stages. This is continuously spreading and affecting more species, both wild and cultured, posing a risk to the development of the aquaculture industry. In the Mediterranean Sea, it mainly affects European sea bass (Dicentrarchus labrax) and some grouper species (Epinephelus spp.). Interestingly, in the gilthead seabream (Sparus aurata), typically resistant to common NNV strains, great mortalities in hatcheries associated with typical clinical signs of VER have been confirmed to be caused by RGNNV/SJNNV reassortants. Thus, we have evaluated the susceptibility of seabream larvae to either RGNNV/SJNNV or SJNNV/RGNNV reassortants, as well as the larval immunity. Based on our results we can conclude that: (i) gilthead seabream larvae are susceptible to infection with both NNV reassortant genotypes, but mainly to RGNNV/SJNNV; (ii) virus replicated and infective particles were isolated; (iii) larval immunity was correlated with larval survival; and (iv) larval resistance and immunity were correlated with age of the larvae. Further investigations should be carried out to ascertain the risks of these new pathogens to Mediterranean larviculture

First Results on Dark Matter Annual Modulation from the ANAIS-112 Experiment

ANAIS is a direct detection dark matter experiment aiming at the testing of the DAMA/LIBRA annual modulation result, which, for about two decades, has neither been confirmed nor ruled out by any other experiment in a model independent way. ANAIS - 112, consisting of 112.5 kg of sodium iodide crystals, has been taking data at the Canfranc Underground Laboratory, Spain, since August 2017. This Letter presents the annual modulation analysis of 1.5 years of data, amounting to 157.55 kg yr. We focus on the model independent analysis searching for modulation and the validation of our sensitivity prospects. ANAIS - 112 data are consistent with the null hypothesis (p values of 0.67 and 0.18 for [2-6] and [1-6] keV energy regions, respectively). The best fits for the modulation hypothesis are consistent with the absence of modulation (S-m = -0.0044 +/- 0.0058 cpd/kg/keV and -0.0015 +/- 0.0063 cpd/kg/keV, respectively). They are in agreement with our estimated sensitivity for the accumulated exposure, which supports our projected goal of reaching a 3 sigma sensitivity to the DAMA/LIBRA result in five years of data taking

The ANAIS-112 experiment at the Canfranc Underground Laboratory

The ANAIS experiment aims at the confirmation of the DAMA/LIBRA signal at the Canfranc Underground Laboratory (LSC). Several 12.5 kg NaI(Tl) modules produced by Alpha Spectra Inc. have been operated there during the last years in various set-ups; an outstanding light collection at the level of 15 photoelectrons per keV, which allows triggering at 1 keV of visible energy, has been measured for all of them and a complete characterization of their background has been achieved. In the first months of 2017, the full ANAIS-112 set-up consisting of nine Alpha Spectra detectors with a total mass of 112.5 kg was commissioned at LSC and the first dark matter run started in August, 2017. Here, the latest results on the detectors performance and measured background from the commissioning run will be presented and the sensitivity prospects of the ANAIS-112 experiment will be discussed