Mass spectrometry imaging identifies palmitoylcarnitine as an immunological mediator during Salmonella Typhimurium infection

Salmonella Typhimurium causes a self-limiting gastroenteritis that may lead to systemic disease. Bacteria invade the small intestine, crossing the intestinal epithelium from where they are transported to the mesenteric lymph nodes (MLNs) within migrating immune cells. MLNs are an important site at which the innate and adaptive immune responses converge but their architecture and function is severely disrupted during S. Typhimurium infection. To further understand host-pathogen interactions at this site, we used mass spectrometry imaging (MSI) to analyse MLN tissue from a murine model of S. Typhimurium infection. A molecule, identified as palmitoylcarnitine (PalC), was of particular interest due to its high abundance at loci of S. Typhimurium infection and MLN disruption. High levels of PalC localised to sites within the MLNs where B and T cells were absent and where the perimeter of CD169+ sub capsular sinus macrophages was disrupted. MLN cells cultured ex vivo and treated with PalC had reduced CD4+CD25+ T cells and an increased number of B220+CD19+ B cells. The reduction in CD4+CD25+ T cells was likely due to apoptosis driven by increased caspase-3/7 activity. These data indicate that PalC significantly alters the host response in the MLNs, acting as a decisive factor in infection outcome

Caenorhabditis elegans: a model to monitor bacterial air quality

<p>Abstract</p> <p>Background</p> <p>Low environmental air quality is a significant cause of mortality and morbidity and this question is now emerging as a main concern of governmental authorities. Airborne pollution results from the combination of chemicals, fine particles, and micro-organisms quantitatively or qualitatively dangerous for health or for the environment. Increasing regulations and limitations for outdoor air quality have been decreed in regards to chemicals and particles contrary to micro-organisms. Indeed, pertinent and reliable tests to evaluate this biohazard are scarce. In this work, our purpose was to evaluate the <it>Caenorhaditis elegans </it>killing test, a model considered as an equivalent to the mouse acute toxicity test in pharmaceutical industry, in order to monitor air bacterial quality.</p> <p>Findings</p> <p>The present study investigates the bacterial population in dust clouds generated during crop ship loading in harbor installations (Rouen harbor, Normandy, France). With a biocollector, airborne bacteria were impacted onto the surface of agar medium. After incubation, a replicate of the colonies on a fresh agar medium was done using a velvet. All the replicated colonies were pooled creating the "Total Air Sample". Meanwhile, all the colonies on the original plate were isolated. Among which, five representative bacterial strains were chosen. The virulence of these representatives was compared to that of the "Total Air Sample" using the <it>Caenorhaditis elegans </it>killing test. The survival kinetic of nematodes fed with the "Total Air Sample" is consistent with the kinetics obtained using the five different representatives strains.</p> <p>Conclusions</p> <p>Bacterial air quality can now be monitored in a one shot test using the <it>Caenorhaditis elegans </it>killing test.</p

Design and Pre-Clinical Evaluation of a Universal HIV-1 Vaccine

BACKGROUND: One of the big roadblocks in development of HIV-1/AIDS vaccines is the enormous diversity of HIV-1, which could limit the value of any HIV-1 vaccine candidate currently under test. METHODOLOGY AND FINDINGS: To address the HIV-1 variation, we designed a novel T cell immunogen, designated HIV(CONSV), by assembling the 14 most conserved regions of the HIV-1 proteome into one chimaeric protein. Each segment is a consensus sequence from one of the four major HIV-1 clades A, B, C and D, which alternate to ensure equal clade coverage. The gene coding for the HIV(CONSV) protein was inserted into the three most studied vaccine vectors, plasmid DNA, human adenovirus serotype 5 and modified vaccine virus Ankara (MVA), and induced HIV-1-specific T cell responses in mice. We also demonstrated that these conserved regions prime CD8(+) and CD4(+) T cell to highly conserved epitopes in humans and that these epitopes, although usually subdominant, generate memory T cells in patients during natural HIV-1 infection. SIGNIFICANCE: Therefore, this vaccine approach provides an attractive and testable alternative for overcoming the HIV-1 variability, while focusing T cell responses on regions of the virus that are less likely to mutate and escape. Furthermore, this approach has merit in the simplicity of design and delivery, requiring only a single immunogen to provide extensive coverage of global HIV-1 population diversity

TG‐69: Radiographic film for megavoltage beam dosimetry

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134818/1/mp6779.pd

Protective Efficacy of Serially Up-Ranked Subdominant CD8+ T Cell Epitopes against Virus Challenges

Immunodominance in T cell responses to complex antigens like viruses is still incompletely understood. Some data indicate that the dominant responses to viruses are not necessarily the most protective, while other data imply that dominant responses are the most important. The issue is of considerable importance to the rational design of vaccines, particularly against variable escaping viruses like human immunodeficiency virus type 1 and hepatitis C virus. Here, we showed that sequential inactivation of dominant epitopes up-ranks the remaining subdominant determinants. Importantly, we demonstrated that subdominant epitopes can induce robust responses and protect against whole viruses if they are allowed at least once in the vaccination regimen to locally or temporally dominate T cell induction. Therefore, refocusing T cell immune responses away from highly variable determinants recognized during natural virus infection towards subdominant, but conserved regions is possible and merits evaluation in humans

Prediction of the amino acid digestibility of legume seeds in growing pigs: a meta-analysis approach

On pig farms, a high proportion of the cost of production comes from feed costs. However, the use of alternative ingredients such as legume seeds may help to reduce this cost. In fact, legume seeds are an important source of essential amino acids (EAA) and can therefore be an alternative to oilseed meals. However, the accurate use of these legume seeds requires a precise knowledge of the standardized ileal digestibility (SID) of EAA, which may vary depending on its botanical variety. A meta-analysis was performed on a database compiling data from 41 studies published between 1981 and 2013 and 178 dietary treatments. Models of prediction of the SID of EAA as well as the dietary concentration of digestible standardized EAA (dEAA) were obtained, based on the chemical composition of ingredients reported in the publications. The effect of the type of legume seeds (faba bean, lupin, pea and soya bean), surgical procedures (T-cannula, re-entrant cannulas, post valve T-cannulas and ileo-rectal anastomosis), and BW of pigs (BW⩽25 kg BW>25 kg) were also tested in each model. Results showed that dietary CP and crude fibre (CF) were, respectively, the best predictors of each EAA SID for faba bean, lupin and pea (R 2=0.42 to 0.89) and soya bean (R 2=0.32 to 0.77). For the dEAA content, the best prediction models included dietary CP and ADF for faba bean, lupin and pea and soya bean, respectively, with R 2 ranging from 0.66 to 0.98. Models developed in this study allow predicting the digestibility of EAA in these alternatives feedstuffs

Effect of limestone particle size on performance, eggshell quality, bone strength, and in vitro/in vivo solubility in laying hens: a meta-analysis approach

International audienceNumerous publications over the past 5 decades have investigated the effect of limestone particle size (LmPS) on production performance, bone mineralization, and limestone solubilization in laying hens. Coarse limestone particles have been shown to improve eggshell quality and bone mineralization. However, there is a large variability of responses in birds to this factor, indicating the need to better quantify the effect of modulating factors related to coarse particles that could explain this variability. The objective of this meta-analysis was to study the impact of LmPS on the digestive and metabolic fate of Ca to optimize its utilization by laying hens. Fifty-eight papers published between 1971 and 2019, including 71 experiments were included in this study. Four categories of dependent variables were identified: Ca solubility, production performance, eggshell quality, and bone strength. Independent variables tested were LmPS and age. Results showed that the in vitro solubilization of limestone linearly decreased (P 0.91): increasing specific gravity by 0.8%, eggshell thickness by 1.1%, and eggshell breaking strength by 3% when increasing from 0.15 mm to 1.5 mm. LmPS had an effect on tibia breaking strength dependently of age (Age × LmPS, P < 0.001; R² = 0.89): coarse limestone particles increased tibia breaking strength with aging compared to fine limestone particles. The current study renders it possible to quantify the effects of age and LmPS on eggshell quality and tibia breaking strength. This work showed an interaction between eggshell quality and bone strength and showed that LmPS increases bone strength in older laying hens

Modelling the digestive utilization of calcium and phosphorus in laying hens

Session 19. Advances in nutritional modelling and feeding systems(in memory of Daniel Sauvant)International audienc

3D computation of a claw pole permanent magnet machine using a scalar potential formulation

In this paper, a claw pole permanent magnet machine is studied using a 3D scalar potential formulation. First, the discretisation of Maxwell's equations using Whitney's elements is presented. Especially, the method to take the winding current distribution into account by means of source fields is detailed. Then, a numerical model of the studied machine is presented. Simulation results (inductance, EMF, torque) are discussed by comparison with experimental ones