Increased Frequency of T Follicular Helper Cells and Elevated Interleukin-27 Plasma Levels in Patients with Pemphigus

Pemphigus is an autoimmune disease in which IgG auto-antibodies (auto-ab) against the desmosomal cadherins desmoglein (Dsg) 3 and Dsg1 cause loss of epidermal keratinocyte adhesion. Aim of this study was to investigate cytokines derived from antigen-presenting cells (APC) and their relation to CD4⁺ T cell subpopulations and to the auto-ab response in pemphigus. In this regard, patients with pemphigus were compared to patients with myasthenia gravis (MG), an unrelated auto-ab–mediated autoimmune disease, and healthy controls. In pemphigus and MG, the plasma concentrations of the APC-derived immunomodulatory cytokine IL-27 were highly increased. Strikingly, IL-27 strongly correlated with Dsg-specific IgG auto-ab titers. T helper (Th) 17 cells were augmented in both pemphigus and MG patients while T follicular helper (Tfh) cells, which are essential in providing B cell help, were increased only in pemphigus along with increasing plasma concentrations of IL-21, a cytokine produced by Th17 and Tfh cells. Moreover, we could detect Dsg3-specific autoreactive T cells producing IL-21 upon ex vivo stimulation with Dsg3. These findings suggest that IL-27 and IL-21-producing T cells, are involved in the pathogenesis of pemphigus. The further characterization of IL-21-producing T cells and of the role of IL-27 will lead to a more defined understanding of the auto-ab response in pemphigus.     

Acceleration Data Reveal Highly Individually Structured Energetic Landscapes in Free-Ranging Fishers (Pekania pennanti)

Investigating animal energy expenditure across space and time may provide more detailed insight into how animals interact with their environment. This insight should improve our understanding of how changes in the environment affect animal energy budgets and is particularly relevant for animals living near or within human altered environments where habitat change can occur rapidly. We modeled fisher (Pekania pennanti) energy expenditure within their home ranges and investigated the potential environmental and spatial drivers of the predicted spatial patterns. As a proxy for energy expenditure we used overall dynamic body acceleration (ODBA) that we quantified from tri-axial accelerometer data during the active phases of 12 individuals. We used a generalized additive model (GAM) to investigate the spatial distribution of ODBA by associating the acceleration data to the animals'' GPS-recorded locations. We related the spatial patterns of ODBA to the utilization distributions and habitat suitability estimates across individuals. The ODBA of fishers appears highly structured in space and was related to individual utilization distribution and habitat suitability estimates. However, we were not able to predict ODBA using the environmental data we selected. Our results suggest an unexpected complexity in the space use of animals that was only captured partially by re-location data-based concepts of home range and habitat suitability. We suggest future studies recognize the limits of ODBA that arise from the fact that acceleration is often collected at much finer spatio-temporal scales than the environmental data and that ODBA lacks a behavioral correspondence. Overcoming these limits would improve the interpretation of energy expenditure in relation to the environment.     

Staphylococcus aureus Sortase A-Mediated Incorporation of Peptides: Effect of Peptide Modification on Incorporation

The endogenous Staphylococcus aureus sortase A (SrtA) transpeptidase covalently anchors cell wall-anchored (CWA) proteins equipped with a specific recognition motif (LPXTG) into the peptidoglycan layer of the staphylococcal cell wall. Previous in situ experiments have shown that SrtA is also able to incorporate exogenous, fluorescently labelled, synthetic substrates equipped with the LPXTG motif (K(FITC)LPETG-amide) into the bacterial cell wall, albeit at high concentrations of 500 μM to 1 mM. In the present study, we have evaluated the effect of substrate modification on the incorporation efficiency. This revealed that (i) by elongation of LPETG-amide with a sequence of positively charged amino acids, derived from the C-terminal domain of physiological SrtA substrates, the incorporation efficiency was increased by 20-fold at 10 μM, 100 μM and 250 μM; (ii) Substituting aspartic acid (E) for methionine increased the incorporation of the resulting K(FITC)LPMTG-amide approximately three times at all concentrations tested; (iii) conjugation of the lipid II binding antibiotic vancomycin to K(FITC)LPMTG-amide resulted in the same incorporation levels as K(FITC)LPETG-amide, but much more efficient at an impressive 500-fold lower substrate concentration. These newly developed synthetic substrates can potentially find broad applications in for example the in situ imaging of bacteria; the incorporation of antibody recruiting moieties; the targeted delivery and covalent incorporation of antimicrobial compounds into the bacterial cell wall.     

Melanoma central nervous system metastases: An update to approaches,challenges, and opportunities

In February 2018, the Melanoma Research Foundation and the Moffitt Cancer Center hosted the Second Summit on Melanoma Central Nervous System (CNS) Metastases in Tampa, Florida. In this white paper, we outline the current status of basic science, translational, and clinical research into melanoma brain metastasis development and therapeutic management. We further outline the important challenges that remain for the field and the critical barriers that need to be overcome for continued progress to be made in this clinically difficult area.     

Life‐history parameters and predation capacity of Macrolophus pygmaeus and Nesidiocoris tenuis (Hemiptera: Miridae) on eggs of Plutella xylostella (Lepidoptera: Plutellidae)

相似文献   

Feeding corn germ instead of corn grain on the performance of Holstein dairy cows fed low-forage diet and human-edible feed conversion efficiency

Using corn germ (CG) instead of corn grain could maintain dairy cow performance and might increase the efficiency of human food production. The primary objective of this study was to evaluate the effects of replacing corn grain with CG on the performance, nutrient intake, and digestibility of dairy cows. It also aimed to investigate the effect of CG on the efficiency of human food production in high-producing Holstein dairy cows in early lactation. Nine multiparous Holstein cows with 65.6 ± 8.5 DIM, milk yield of 55.6 ± 4.5 kg/d, and body weight of 611.3 ± 43.3 kg (mean ± SD) were used in a 3 × 3 Latin square design with 21-d periods. Treatments were (1) control treatment (CT, diet contains corn grain), (2) alternative treatment (AT, diet where corn grain was replaced with CG), and (3) balanced treatment (BT, diet where corn grain was replaced with CG but with the same energy content as CT). Control and balanced diets were isoenergetic (6.61 MJ/kg of DM); however, AT had higher energy (6.77 MJ/kg of DM). Treatments had no effect on dry and organic matter intake. NDF intake, however, was higher in CG diets compared with CT (P = 0.0001). Total-tract digestibility of DM tended to be reduced (P = 0.08), and OM digestibility was reduced (P = 0.05) by the inclusion of CG in diets. Whole and energy-corrected milk production were greater in AT compared with CT and BT (P < 0.05). Milk yield was similar in cows fed CT and BT. Treatments had no effect on milk composition or feed efficiency. Diet CT, when compared with CG diets, had lower efficiency in terms of human-edible feed conversion efficiency (HeFCE) and net food production (P < 0.05). Diet BT had greater HeFCE and net production of human-edible CP than AT (P < 0.05). Plasma BHBA, non-esterified fatty acids, and glucose concentrations were not affected by treatments, but plasma cholesterol was higher in cows that consumed CG diets (P = 0.04). The results indicate that, in high-producing early lactation dairy cows fed high concentrate diets, net food protein production can be substantially improved without lowering milk production through the reduction of dietary starch from 30.2 to 24.8% by replacing corn grain with CG.