Host genetic makeup plays a role in early gut microbial colonization and immune programming. Interactions between gut microbiota and host cells of the mucosal layer are of paramount importance for a ...proper development of host defence mechanisms. For different livestock species, it has already been shown that particular genotypes have increased susceptibilities towards disease causing pathogens. The objective of this study was to investigate the impact of genotypic variation on both early microbial colonization of the gut and functional development of intestinal tissue. From two genetically diverse chicken lines intestinal content samples were taken for microbiota analyses and intestinal tissue samples were extracted for gene expression analyses, both at three subsequent time-points (days 0, 4, and 16).
The microbiota composition was significantly different between lines on each time point. In contrast, no significant differences were observed regarding changes in the microbiota diversity between the two lines throughout this study. We also observed trends in the microbiota data at genus level when comparing lines X and Y. We observed that approximately 2000 genes showed different temporal gene expression patterns when comparing line X to line Y. Immunological related differences seem to be only present at day 0, because at day 4 and 16 similar gene expression is observed for these two lines. However, for genes involved in cell cycle related processes the data show higher expression over the whole course of time in line Y in comparison to line X.
These data suggest the genetic background influences colonization of gut microbiota after hatch in combination with the functional development of intestinal mucosal tissue, including the programming of the immune system. The results indicate that genetically different chicken lines have different coping mechanisms in early life to cope with the outside world.
Background and Objective
The tacrolimus concentration within peripheral blood mononuclear cells may correlate better with clinical outcomes after transplantation compared to concentrations measured ...in whole blood. However, intracellular tacrolimus measurements are not easily implemented in clinical practice. The prediction of intracellular concentrations based on whole-blood concentrations would be a solution for this. Therefore, the aim of this study was to describe the relationship between intracellular and whole-blood tacrolimus concentrations in a population pharmacokinetic (popPK) model.
Methods
Pharmacokinetic analysis was performed using non-linear mixed effects modelling software (NONMEM). The final model was evaluated using goodness-of-fit plots, visual predictive checks, and a bootstrap analysis.
Results
A total of 590 tacrolimus concentrations from 184 kidney transplant recipients were included in the study. All tacrolimus concentrations were measured in the first three months after transplantation. The intracellular tacrolimus concentrations (
n
= 184) were best described with an effect compartment. The distribution into the effect compartment was described by the steady-state whole-blood to intracellular ratio (
R
WB:IC
) and the intracellular distribution rate constant between the whole-blood and intracellular compartments. Lean body weight was negatively correlated delta objective function value (ΔOFV) −8.395 and haematocrit was positively correlated (ΔOFV = − 6.752) with
R
WB:IC
, and both lean body weight and haematocrit were included in the final model.
Conclusion
We were able to accurately describe intracellular tacrolimus concentrations using whole-blood concentrations, lean body weight, and haematocrit values in a popPK model. This model may be used in the future to more accurately predict clinical outcomes after transplantation and to identify patients at risk for under- and overexposure.
Dutch National Trial Registry number NTR2226
The effects of herbivores on plant production and fitness may not relate directly to the quantity of biomass removed because folivory may alter photosynthetic rates at a considerable distance from ...the damaged tissue Welter, S. C. (1989) in Insect-Plant Interactions, ed. Bernays, E. A. (CRC, Boca Raton), pp. 135-151.. An impediment to understanding the effects of leaf damage on photosynthesis has been an inability to map photosynthetic function within a single leaf. We developed an instrument for imaging chlorophyll fluorescence and used it to map the effects of caterpillar feeding on whole-leaf photosynthesis in wild parsnip. The adverse effects of caterpillar feeding on photosynthesis were found to extend well beyond the areas of the leaflet in which caterpillars removed tissue. These "indirectly" affected areas remained impaired for at least 3 days after the caterpillars were removed and were six times as large as the area directly damaged by the caterpillars. Although photosynthesis in indirectly affected areas was reduced and not eliminated, these areas accounted for three times as much of the overall reduction in photosynthesis as the area removed by the caterpillars. The size of the indirect effects was positively correlated with defense-related synthesis of furanocoumarins, suggesting that costs of chemical defense may be one factor that accounts for the indirect effects of herbivory on plants.
The interleukin-27 (IL-27)/T-cell cytokine receptor (TCCR) pathway plays an important role in development of protective immunity against cutaneous leishmaniasis caused by
Leishmania major.
In this ...study, we analyzed the role of IL-27/TCCR pathway in the host defense against visceral leishmaniasis (VL) by monitoring the course of
L. donovani
infection in TCCR-deficient C57BL/6 (TCCR−/−) mice. TCCR−/− mice mounted a robust inflammatory response, produced high levels of pro-inflammatory cytokines, and developed severe liver pathology after
L. donovani
infection that eventually resolved. Interestingly,
L. donovani
-infected TCCR−/− mice controlled the parasite growth in their organs significantly faster than similarly infected TCCR+/+ mice. Adoptive cell transfer and cell depletion studies revealed that CD4
+ T cells were involved in mediating liver immunopathology and controlling
L. donovani
growth in TCCR−/− mice. These results indicate that the IL-27/TCCR pathway is not essential for the induction of protective Th1 response during VL but is involved in mediating susceptibility to
L. donovani
. Additionally, the data demonstrate that although the IL-27/TCCR interaction limits the severity of liver inflammation during VL by controlling CD4
+ T-cell activity, it is not required for the resolution of hepatic immunopathology.
The background induced by the high penetration power of the radiation is the main limiting factor of the current radio-guided surgery (RGS). To partially mitigate it, a RGS with β(+)-emitting ...radio-tracers has been suggested in literature. Here we propose the use of β(-)-emitting radio-tracers and β(-) probes and discuss the advantage of this method with respect to the previously explored ones: the electron low penetration power allows for simple and versatile probes and could extend RGS to tumours for which background originating from nearby healthy tissue makes probes less effective. We developed a β(-) probe prototype and studied its performances on phantoms. By means of a detailed simulation we have also extrapolated the results to estimate the performances in a realistic case of meningioma, pathology which is going to be our first in-vivo test case. A good sensitivity to residuals down to 0.1 ml can be reached within 1 s with an administered activity smaller than those for PET-scans thus making the radiation exposure to medical personnel negligible.
Hadrontherapy is an emerging technique in cancer therapy that uses beams of charged particles. To meet the improved capability of hadrontherapy in matching the dose release with the cancer position, ...new dose-monitoring techniques need to be developed and introduced into clinical use. The measurement of the fluxes of the secondary particles produced by the hadron beam is of fundamental importance in the design of any dose-monitoring device and is eagerly needed to tune Monte Carlo simulations. We report the measurements carried out with charged secondary particles produced from the interaction of a 80 MeV/u fully stripped carbon ion beam at the INFN Laboratori Nazionali del Sud, Catania, with a poly-methyl methacrylate target. Charged secondary particles, produced at 90° with respect to the beam axis, have been tracked with a drift chamber, while their energy and time of flight have been measured by means of a LYSO scintillator. Secondary protons have been identified exploiting the energy and time-of-flight information, and their emission region has been reconstructed backtracking from the drift chamber to the target. Moreover, a position scan of the target indicates that the reconstructed emission region follows the movement of the expected Bragg peak position. Exploiting the reconstruction of the emission region, an accuracy on the Bragg peak determination in the submillimeter range has been obtained. The measured differential production rate for protons produced with E(Prod)(kin) > 83 MeV and emitted at 90° with respect to the beam line is dN(P)/(dN(C)dΩ) (E(Prod)(kin) > 83 MeV, θ = 90°) = (2.69 ± 0.08(stat) ± 0.12(sys)) × 10⁻⁴ sr⁻¹.
Mycobacterium leprae infects macrophages and Schwann cells inducing a gene expression program to facilitate its replication and progression to disease. MicroRNAs (miRNAs) are key regulators of gene ...expression and could be involved during the infection. To address the genetic influence of miRNAs in leprosy, we enrolled 1,098 individuals and conducted a case-control analysis in order to study four miRNAs genes containing single nucleotide polymorphism (miRSNP). We tested miRSNP-125a (rs12975333 G>T), miRSNP-223 (rs34952329 *>T), miRSNP-196a-2 (rs11614913 C>T) and miRSNP-146a (rs2910164 G>C). Amongst them, miRSNP-146a was the unique gene associated with risk to leprosy per se (GC OR = 1.44, p = 0.04; CC OR = 2.18, p = 0.0091). We replicated this finding showing that the C-allele was over-transmitted (p = 0.003) using a transmission-disequilibrium test. A functional analysis revealed that live M. leprae (MOI 100:1) was able to induce miR-146a expression in THP-1 (p<0.05). Furthermore, pure neural leprosy biopsies expressed augmented levels of that miRNA as compared to biopsy samples from neuropathies not related with leprosy (p = 0.001). Interestingly, carriers of the risk variant (C-allele) produce higher levels of mature miR-146a in nerves (p = 0.04). From skin biopsies, although we observed augmented levels of miR-146a, we were not able to correlate it with a particular clinical form or neither host genotype. MiR-146a is known to modulate TNF levels, thus we assessed TNF expression (nerve biopsies) and released by peripheral blood mononuclear cells infected with BCG Moreau. In both cases lower TNF levels correlates with subjects carrying the risk C-allele, (p = 0.0453 and p = 0.0352; respectively), which is consistent with an immunomodulatory role of this miRNA in leprosy.
Status of the cylindrical-GEM project for the KLOE-2 inner tracker Balla, A.; Bencivenni, G.; Cerioni, S. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
02/2011, Volume:
628, Issue:
1
Journal Article
Peer reviewed
Open access
The status of the R&D on the Cylindrical-GEM (CGEM) detector foreseen as inner tracker for KLOE-2, the upgrade of the KLOE experiment at the
DA
Φ
NE
φ
-factory
, is presented. The R&D includes ...several activities: (i) the construction and complete characterization of the full-size CGEM prototype, equipped with
650
μ
m
pitch 1-D longitudinal strips; (ii) the study of the 2-D readout with XV patterned strips and operation in magnetic field (up to 1.5
T), performed with small planar prototypes in a dedicated test at the H4-SPS beam facility; (iii) the characterization of the single-mask GEM technology for the realization of large-area GEM foils.
The diagnostic performance of an ELISA for the detection of antibodies to the small ruminant lentiviruses (SRLVs) maedi-visna virus and caprine arthritis-encephalitis virus in milk and corresponding ...blood samples was evaluated in 50 sheep. The agreement between ELISA results in blood and milk was 90 per cent, and the κ value was 0.79. In addition, a serological survey in the central zone of Spain was performed using milk samples from 413 animals (250 sheep and 163 goats) from 12 flocks/herds. All flocks/herds had some animals that were positive for SRLV. Among the animals, 60.0 per cent of the sheep and 8.0 per cent of the goats tested were seropositive. Each sample was also tested using a PCR technique, which increased the percentage of positive animals detected. Using a combination of ELISA and PCR gave a total of 72.2 per cent of sheep and 28.8 per cent of goats positive for SRLV.
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