Proresolving lipid mediators resolvin D1, resolvin D2, and maresin 1 are critical in modulating T cell responses.

Resolution of inflammation is a finely regulated process mediated by specialized proresolving lipid mediators (SPMs), including docosahexaenoic acid (DHA)-derived resolvins and maresins. The immunomodulatory role of SPMs in adaptive immune cells is of interest. We report that D-series resolvins (resolvin D1 and resolvin D2) and maresin 1 modulate adaptive immune responses in human peripheral blood lymphocytes. These lipid mediators reduce cytokine production by activated CD8(+) T cells and CD4(+) T helper 1 (TH1) and TH17 cells but do not modulate T cell inhibitory receptors or abrogate their capacity to proliferate. Moreover, these SPMs prevented naïve CD4(+) T cell differentiation into TH1 and TH17 by down-regulating their signature transcription factors, T-bet and Rorc, in a mechanism mediated by the GPR32 and ALX/FPR2 receptors; they concomitantly enhanced de novo generation and function of Foxp3(+) regulatory T (Treg) cells via the GPR32 receptor. These results were also supported in vivo in a mouse deficient for DHA synthesis (Elovl2(-/-)) that showed an increase in TH1/TH17 cells and a decrease in Treg cells compared to wild-type mice. Additionally, either DHA supplementation in Elovl2(-/-) mice or in vivo administration of resolvin D1 significantly reduced cytokine production upon specific stimulation of T cells. These findings demonstrate actions of specific SPMs on adaptive immunity and provide a new avenue for SPM-based approaches to modulate chronic inflammation.This work was supported by Fondazione Italiana Sclerosi Multipla (FISM) to V.C. (grant 2015/R/8) and in part by National Institutes of Health (P01095467 and GM38765) to C.N.S, by Ministero dell’Istruzione, dell’Università e della Ricerca (PRIN grant 2010–2011) to M.M., and by Ministero della Salute (RF-2011- 02346771) and FISM (grant 2013/R/2) to L.B

Protective effects of the lazaroid U74500A and lidoflazine on liver preservation with UW solution

The effect of adding a 21-aminosteroid, U74500A, and a Ca2+ antagonist, lidoflazine, alone and together to UW solution was assessed in a rat liver preservation model. Following preservation, the livers were reperfused using a closed circuit, and the release of hepatocellular enzymes (ASAT, ALAT, and LDH) into the perfusate was determined with increasing time. Both drugs reduced the amount of enzymes lost from the liver. The combination of the two drugs was better than either drug alone. These data suggest that both agents may be of value in organ preservation for clinical liver transplantation. © 1993 Springer-Verlag

Proposal to Search for Heavy Neutral Leptons at the SPS

A new fixed-target experiment at the CERN SPS accelerator is proposed that will use decays of charm mesons to search for Heavy Neutral Leptons (HNLs), which are right-handed partners of the Standard Model neutrinos. The existence of such particles is strongly motivated by theory, as they can simultaneously explain the baryon asymmetry of the Universe, account for the pattern of neutrino masses and oscillations and provide a Dark Matter candidate. Cosmological constraints on the properties of HNLs now indicate that the majority of the interesting parameter space for such particles was beyond the reach of the previous searches at the PS191, BEBC, CHARM, CCFR and NuTeV experiments. For HNLs with mass below 2 GeV, the proposed experiment will improve on the sensitivity of previous searches by four orders of magnitude and will cover a major fraction of the parameter space favoured by theoretical models. The experiment requires a 400 GeV proton beam from the SPS with a total of 2x10^20 protons on target, achievable within five years of data taking. The proposed detector will reconstruct exclusive HNL decays and measure the HNL mass. The apparatus is based on existing technologies and consists of a target, a hadron absorber, a muon shield, a decay volume and two magnetic spectrometers, each of which has a 0.5 Tm magnet, a calorimeter and a muon detector. The detector has a total length of about 100 m with a 5 m diameter. The complete experimental set-up could be accommodated in CERN's North Area. The discovery of a HNL would have a great impact on our understanding of nature and open a new area for future research

Design of a high power production target for the Beam Dump Facility at CERN

The Beam Dump Facility (BDF) project is a proposed general-purpose facility at CERN, dedicated to beam dump and fixed target experiments. In its initial phase, the facility is foreseen to be exploited by the Search for Hidden Particles (SHiP) experiment. Physics requirements call for a pulsed 400 GeV/c proton beam as well as the highest possible number of protons on target (POT) each year of operation, in order to search for feebly interacting particles. The target/dump assembly lies at the heart of the facility, with the aim of safely absorbing the full high intensity Super Proton Synchrotron (SPS) beam, while maximizing the production of charmed and beauty mesons. High-Z materials are required for the target/dump, in order to have the shortest possible absorber and reduce muon background for the downstream experiment. The high average power deposited on target (305 kW) creates a challenge for heat removal. During the BDF facility Comprehensive Design Study (CDS), launched by CERN in 2016, extensive studies have been carried out in order to define and assess the target assembly design. These studies are described in the present contribution, which details the proposed design of the BDF production target, as well as the material selection process and the optimization of the target configuration and beam dilution. One of the specific challenges and novelty of this work is the need to consider new target materials, such as a molybdenum alloy (TZM) as core absorbing material and Ta2.5W as cladding. Thermo-structural and fluid dynamics calculations have been performed to evaluate the reliability of the target and its cooling system under beam operation. In the framework of the target comprehensive design, a preliminary mechanical design of the full target assembly has also been carried out, assessing the feasibility of the whole target system.Comment: 17 pages, 18 figure

Towards mapping the brain connectome in depression: functional connectivity by perfusion SPECT

Several studies have demonstrated altered brain functional connectivity in the resting state in depression. However, no study investigated interregional networking in patients with persistent depressive disorder (PDD). The aim of this study was to assess differences in brain perfusion distribution and connectivity between large groups of patients and healthy controls. Participants comprised 91 patients with PDD and 65 age- and sex-matched healthy controls. Resting-state perfusion was investigated by single photon emission computed tomography and group differences were assessed by Statistical Parametric Mapping. Brain connectivity was explored through a voxel-wise interregional correlation analysis using as covariate of interest the normalized values of clusters of voxels in which perfusion differences were found at group analysis. Significantly increased regional brain perfusion distribution covering a large part of the cerebellum was observed in patients as compared to controls. Patients showed significantly negative functional connectivity between the cerebellar cluster and caudate, bilaterally. This study demonstrated inverse relative perfusion between cerebellum and caudate in PDD. Functional uncoupling may be associated with a dysregulation between the role of cerebellum in action control and of the caudate action selection, initiation and decision making in the patients. The possible impact of the resting-state condition and of mitochondrial impairment are discussed

Fatigue testing of a proximal femoral hip component

Published versio

BDNF polymorphisms are linked to poorer working memory performance, reduced cerebellar and hippocampal volumes and differences in prefrontal cortex in a Swedish elderly population

BACKGROUND: Brain-derived neurotrophic factor (BDNF) links learning, memory and cognitive decline in elderly, but evidence linking BDNF allele variation, cognition and brain structural differences is lacking. METHODS: 367 elderly Swedish men (n = 181) and women (n = 186) from Prospective Investigation of the Vasculature in Uppsala seniors (PIVUS) were genotyped and the BDNF functional rs6265 SNP was further examined in subjects who completed the Trail Making Task (TMT), verbal fluency task, and had a magnetic resonance imaging (MRI) scan. Voxel-based morphometry (VBM) examined brain structure, cognition and links with BDNF. RESULTS: The functional BDNF SNP (rs6265,) predicted better working memory performance on the TMT with positive association of the Met rs6265, and was linked with greater cerebellar, precuneus, left superior frontal gyrus and bilateral hippocampal volume, and reduced brainstem and bilateral posterior cingulate volumes. CONCLUSIONS: The functional BDNF polymorphism influences brain volume in regions associated with memory and regulation of sensorimotor control, with the Met rs6265 allele potentially being more beneficial to these functions in the elderly

Shotgun Phage Display - Selection for Bacterial Receptins or other Exported Proteins

Shotgun phage display cloning involves construction of libraries from randomly fragmented bacterial chromosomal DNA, cloned genes, or eukaryotic cDNAs, into a phagemid vector. The library obtained consists of phages expressing polypeptides corresponding to all genes encoded by the organism, or overlapping peptides derived from the cloned gene. From such a library, polypeptides with affinity for another molecule can be isolated by affinity selection, panning. The technique can be used to identify bacterial receptins and identification of their minimal binding domain, and but also to identify epitopes recognised by antibodies. In addition, after modification of the phagemid vector, the technique has also been used to identify bacterial extracytoplasmic proteins