Search

Item does not contain fulltext Membrane cholesterol modulates a variety of cell signaling pathways and functions. While cholesterol depletion by high-density lipoproteins (HDLs) has potent anti-inflammatory effects in various cell types, its effects on inflammatory responses in macrophages remain elusive. Here we show overt pro-inflammatory effects of HDL-mediated passive cholesterol depletion and lipid raft disruption in murine and human primary macrophages in vitro. These pro-inflammatory effects were confirmed in vivo in peritoneal macrophages from apoA-I transgenic mice, which have elevated HDL levels. In line with these findings, the innate immune responses required for clearance of P. aeruginosa bacterial infection in lung were compromised in mice with low HDL levels. Expression analysis, ChIP-PCR, and combinatorial pharmacological and genetic intervention studies unveiled that both native and reconstituted HDL enhance Toll-like-receptor-induced signaling by activating a PKC-NF-kappaB/STAT1-IRF1 axis, leading to increased inflammatory cytokine expression. HDL's pro-inflammatory activity supports proper functioning of macrophage immune responses.

Scientific reports 7(1), 11670 (2017). doi:10.1038/s41598-017-10549-x, Published by Nature Publishing Group, London

Nestling development and long-term survival in many bird species depend on factors such as parental feeding, time of breeding and environmental conditions. However, little research has been carried out on the effect of ectoparasites on nestling development, and no research on the impact of the trophic structure of arthropods inhabiting the nest (combined effects of ectoparasitic mites and predatory mites feeding on ectoparasites). We assess nestling development of European Starlings (Sturnus vulgaris) in relation to the number of parasitic mites Dermanyssus gallinae (DG, a blood-sucking mite) and their predators, i.e. Androlaelaps casalis (AC), both dominant species of nidicolous arthropods in Starling nests. DG densities were not associated with nestling body mass or tarsus length during development (10 and 17 days of age), which contradicts our expectation that parasitic mites negatively influence growth. Furthermore, an increase in AC densities was associated with a significant decrease in body mass (not tarsus length) later during nestling development (at day 17—a proxy for nestling age—but not at day 10). The latter seems counterintuitive, but not when the inherent density-dependent delays in Lotka-Volterra predator–prey interactions are taken into account: a high density of predatory mites (AC) always arises after an increase of prey mites (DG). Thus, the high density of predatory mites indicates a preceding peak density of parasitic mites. Clearly, this explanation requires insight in the trophic structure of mites inhabiting Starling nests and bird nests in general. We conclude that multitrophic interactions (between predator, parasite and host) in nests should not be ignored when assessing nestling development.

SummaryThe phenotype of macrophages in atherosclerotic lesions can vary dramatically, from a large lipid laden foam cell to a small inflammatory cell. Classically, the concept of macrophage heterogeneity discriminates between two extremes called either pro-inflammatory M1 macrophages or anti-inflammatory M2 macrophages. Polarisation of plaque macrophages is predominantly determined by the local micro-environment present in the atherosclerotic lesion and is rather more complex than typically described by the M1/M2 paradigm. In this review we will discuss the role of various polarising factors in regulating the phenotypical state of plaque macrophages. We will focus on two main levels of phenotype regulation, one determined by differentiation factors produced in the lesion and the other determined by T-cell-derived polarising cytokines. With foam cell formation being a key characteristic of macrophages during atherosclerosis initiation and progression, these polarisation factors will also be linked to lipid handling of macrophages.

The poultry red mite, Dermanyssus gallinae, is currently a significant pest in the poultry industry in Europe. Biological control by the introduction of predatory mites is one of the various options for controlling poultry red mites. Here, we present the first results of an attempt to identify potential predators by surveying the mite fauna of European starling (Sturnus vulgaris) nests, by assessing their ability to feed on poultry red mites and by testing for their inability to extract blood from bird hosts, i.e., newly hatched, young starlings and chickens. Two genuine predators of poultry red mites are identified: Hypoaspis aculeifer and Androlaelaps casalis. A review of the literature shows that some authors suspected the latter species to parasitize on the blood of birds and mammals, but they did not provide experimental evidence for these feeding habits and/or overlooked published evidence showing the reverse. We advocate careful analysis of the trophic structure of arthropods inhabiting bird nests as a basis for identifying candidate predators for control of poultry red mites.

Background— Leukocyte migration is critical for the infiltration of monocytes and accumulation of monocyte-derived macrophages in inflammation. Considering that Hck and Fgr are instrumental in this process, their impact on atherosclerosis and on lesion inflammation and stability was evaluated. Methods and Results— Hematopoietic Hck/Fgr-deficient, LDLr −/− chimeras, obtained by bone marrow transplantation, had smaller but, paradoxically, less stable lesions with reduced macrophage content, overt cap thinning, and necrotic core expansion as the most prominent features. Despite a Ly6C high -skewed proinflammatory monocyte phenotype, Hck/Fgr deficiency led to disrupted adhesion of myeloid cells to and transmigration across endothelial monolayers in vitro and atherosclerotic plaques in vivo, as assessed by intravital microscopy, flow cytometry, and histological examination of atherosclerotic arteries. Moreover, Hck/Fgr-deficient macrophages showed blunted podosome formation and mesenchymal migration capacity. In consequence, transmigrated double-knockout macrophages were seen to accumulate in the fibrous cap, potentially promoting its focal erosion, as observed for double-knockout chimeras. Conclusions— The hematopoietic deficiency of Hck and Fgr led to attenuated atherosclerotic plaque formation by abrogating endothelial adhesion and transmigration; paradoxically, it also promoted plaque instability by causing monocyte subset imbalance and subendothelial accumulation, raising a note of caution regarding src kinase–targeted intervention in plaque inflammation.

Atherosclerosis is a lipid-driven inflammatory disease of the vessel wall, characterized by the chronic activation of macrophages. We investigated whether the helminth-derived antigens [soluble egg antigens (SEAs)] could modulate macrophage inflammatory responses and protect against atherosclerosis in mice. In bone marrow-derived macrophages, SEAs induce anti-inflammatory macrophages, typified by high levels of IL-10 and reduced secretion of proinflammatory mediators. In hyperlipidemic LDLR-/- mice, SEA treatment reduced plaque size by 44%, and plaques were less advanced compared with PBS-injected littermate controls. The atheroprotective effect of SEAs was found to be mainly independent of cholesterol lowering and T-lymphocyte responses but instead could be attributed to diminished myeloid cell activation. SEAs reduced circulating neutrophils and inflammatory Ly6C(high) monocytes, and macrophages showed high IL-10 production. In line with the observed systemic effects, atherosclerotic lesions of SEA-treated mice showed reduced intraplaque inflammation as inflammatory markers [TNF-, monocyte chemotactic protein 1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and CD68], neutrophil content, and newly recruited macrophages were decreased. We show that SEA treatment protects against atherosclerosis development by dampening inflammatory responses. In the future, helminth-derived components may provide novel opportunities to treat chronic inflammatory diseases, as they diminish systemic inflammation and reduce the activation of immune cells.Wolfs, I. M. J., Stoger, J. L., Goossens, P., Pottgens, C., Gijbels, M. J. J., Wijnands, E., van der Vorst, E. P. C., van Gorp, P., Beckers, L., Engel, D., Biessen, E. A. L., Kraal, G., van Die, I., Donners, M. M. P. C., de Winther, M. P. J. Reprogramming macrophages to an anti-inflammatory phenotype by helminth antigens reduces murine atherosclerosis.

microRNA-155 (miR155) is a central regulator of immune responses that is induced by inflammatory mediators. Although miR155 is considered to be a pro-inflammatory microRNA, in vitro reports show anti-inflammatory effects in lipid-loaded cells. In this study we examined the role of miR155 in atherosclerosis in vivo using bone marrow transplantation from miR155 deficient or wildtype mice to hyperlipidemic mice. Hematopoietic deficiency of miR155 enhanced atherosclerotic plaque development and decreased plaque stability, as evidenced by increased myeloid inflammatory cell recruitment to the plaque. The increased inflammatory state was mirrored by a decrease in circulating CD4(+)CD25(+)FoxP3(+) regulatory T cells, and an increase in granulocytes (CD11b(+)Ly6G(+)) in blood of miR155(-/-) transplanted mice. Moreover, we show for the first time a crucial role of miR155 in monocyte subset differentiation, since hematopoietic deficiency of miR155 increases the 'inflammatory' monocyte subset (CD11b(+)Ly6G(-)Ly6C(hi)) and reduces 'resident' monocytes (CD11b(+)Ly6G(-)Ly6C(low)) in the circulation. Furthermore, cytokine production by resident peritoneal macrophages of miR155(-/-) transplanted hyperlipidemic mice was skewed towards a more pro-inflammatory state since anti-inflammatory IL-10 production was reduced. In conclusion, in this hyperlipidemic mouse model miR155 acts as an anti-inflammatory, atheroprotective microRNA. Additionally, besides a known role in lymphoid cell development, we show a crucial role of miR155 in myeloid lineage differentiation.

Emerging wireless sensor networking (WSN) and modern machine learning techniques have encouraged interest in the development of vehicle health monitoring (VHM) systems that ensure secure and reliable operation of the rail vehicle. The performance of rail vehicles running on railway tracks is governed by the dynamic behaviours of railway bogies especially in the cases of lateral instability and track irregularities. In order to ensure safety and reliability of railway in this chapter, a forecasting model has been developed to investigate vertical acceleration behaviour of railway wagons attached to a moving locomotive using modern machine learning techniques. Initially, an energy-efficient data acquisition model has been proposed for WSN applications using popular learning algorithms. Later, a prediction model has been developed to investigate both front and rear body vertical acceleration behaviour. Different types of models can be built using a uniform platform to evaluate their performances and estimate different attributes’ correlation coefficient (CC), root mean square error (RMSE), mean absolute error (MAE), root relative squared error (RRSE), relative absolute error (RAE) and computation complexity for each of the algorithm. Finally, spectral analysis of front and rear body vertical condition is produced from the predicted data using Fast Fourier Transform (FFT) and used to generate precautionary signals and system status which can be used by the locomotive driver for deciding upon necessary actions.

Attention and expectancy have, in previous research, been demonstrated to influence symptom reporting and these findings can be relevant for understanding hypochondriasis. Earlier attention/expectancy effects on symptom reporting were studied when subjects were physically stimulated by the experimenter. If attention or expectancy produced symptom reporting, which plays a role in hypochondriasis, one expects that attention/expectancy will also produce symptoms in the absence of any deliberate physical stimulation. Eighty healthy volunteers were allocated to one of four groups: attention, expectancy, attention plus expectancy or a control condition. Compared to the control condition there was much higher symptom reporting in the 3 experimental groups. The experimental groups did not differ. It is argued that the effects of expectancy are obtained via increased attention. The relevance of the findings for understanding hypochondriasis is discussed.

Objective— To elucidate the downstream mechanisms of vascular endothelial growth factor receptor 2 (VEGFR2), a key receptor in angiogenesis, which has been associated with atherosclerotic plaque growth and instability. Methods and Results— By using a yeast–2-hybrid assay, we identified A D isintegrin A nd M etalloprotease 10 (ADAM10) as a novel binding partner of VEGFR2. ADAM10 is a metalloprotease with sheddase activity involved in cell migration; however, its exact function in endothelial cells (ECs), angiogenesis, and atherosclerosis is largely unknown. For the first time to our knowledge, we show ADAM10 expression in human atherosclerotic lesions, associated with plaque progression and neovascularization. We demonstrate ADAM10 expression and activity in ECs to be induced by VEGF; also, ADAM10 mediates the ectodomain shedding of VEGFR2. Furthermore, VEGF induces ADAM10-mediated cleavage of vascular endothelium (VE)-cadherin, which could increase vascular permeability and facilitate EC migration. Indeed, VEGF increases vascular permeability in an ADAM10- and ADAM17-dependent way; inhibition of ADAM10 reduces EC migration and chemotaxis. Conclusion— These data provide the first evidence of ADAM10 expression in atherosclerosis and neovascularization. ADAM10 plays a functional role in VEGF-induced EC function. These data open perspectives for novel therapeutic interventions in vascular diseases.

Background: Studies on effectiveness of phytosterol/-stanol-enriched margarines in the community have received low priority. For postlaunch monitoring purposes including risk-benefit analyses, it is needed to investigate both exposure and effectiveness of these margarines. Objective: To study the use and effectiveness of phytosterol/-stanol-enriched margarine. Design, setting and subjects: The study population consisted of 2379 subjects that participated in a community intervention study ('Hartslag Limburg') aged 28-76 years. In 1998 and 2003, blood samples for total and high- density lipoprotein (HDL) cholesterol were obtained. A general questionnaire and food frequency questionnaire (FFQ) were administered. From 1999 onwards, phytosterol/-stanol-enriched margarines were introduced on the Dutch market. On the basis of 2003 data, subjects were classified in users of (a) phytosterol/-stanol-enriched margarine, (b) cholesterol-lowering drugs, (c) the combination (both enriched margarine and drugs) and (d) neither enriched margarines nor cholesterol-lowering drugs. Results: Mean (+/- s.d.) daily intake of phytosterol-enriched margarine (n=99) and phytostanol-enriched margarine (n=16) was 14 +/- 9 g. From 1998 to 2003, total serum cholesterol concentration changed significantly different among the four groups: in the combination users -2.04 +/- 1.50 mmol/l (-29%), in cholesterol-lowering drug users -1.09 +/- 1.17 mmol/l (-17%), in the enriched margarine users -0.24 +/- 0.75 mmol/l (-4%) and in non-users +0.10 +/- 0.72 mmol/l (+2%)(P

We report on the mechanisms, the environmental changes and patient compliance with regard to conventional and new dust and mite avoidance measures to prevent allergic symptoms caused by mite allergens, taking into account both allergen contamination and the developmental success of pyroglyphid Acari. Twenty patients with persisting rhinitic complaints were selected and matched. Although the patients had performed some conventional dust and mite avoidance measures (patient compliance was 90%), the dwellings proved to be a stimulus for mite development. Moisture problems due to faulty construction and excessive moisture production were common. Since humidity conditions could not be changed at short notice, the 20 homes were subjected to the new variants of mite allergen avoidance based on intensive cleaning without (control) and with an acaricide incorporated (acaricidal cleaner [Acarosan]). After the carrying out of conventional avoidance measures, these patients still had allergic symptoms, and dust from only 23 to 52% of their textile objects was under the proposed guanine (mite faeces indicator) risk level. Only the acaricidal cleaner was able to decrease the allergenic mite load (and the burden of the patients) significantly in this 12 month period. With respect to mite-extermination, acaricidal cleaning was 88% better than intensive cleaning. Reduction of guanine was 38% better in the Acarosan treatment group. Clinical results have been reported elsewhere. A significant difference in favour of the acaricidal cleaning was seen in both subjective (as regards symptoms) and in objective data (total IgE). Another 50 patients were questioned. About 90% were willing to spend two weekends (70%), or at the most one weekend (20%) per year sanitizing the dwelling by cleaning it with the whole family. The authors of this report consider acaricidal cleaning to be a significant improvement in the management of mite-allergic diseases, such as rhinitis. Compared with the replacement of home textiles, this treatment is less expensive and more effective. Patient compliance is acceptable, but depends on acceptance by physicians and the initial motivation and consequent burden on the patient.

Several field and laboratory experiments were performed to study the impact of acidification on the decomposition of Juncus bulbosus L. The breakdown of coarse detritus of this aquatic macrophyte appeared to be very slow. After 7 weeks of incubation in an acidified and a circumneutral moorland pool the remaining fraction of Juncus leaves varied between 46 and 75% of the original organic weight. Differences in decay patterns were observed among both systems. Furthermore, the breakdown rates were highly dependent on the season. Highest weight loss rates were recorded at high pH during the summer period. In acidified water and during the winter period the breakdown rates were reduced. Nutrient dynamics of detritus in the circumneutral soft water and the acidified system differed remarkably. In litter bags laid down on the bottom surface of the acidified moorland pool the density and diversity of macroinvertebrate assemblages was generally lower than in the bags immersed in the non-acidified body of water. In particular, the abundance of detritivores and herbivores at low pH was strongly reduced. However, in winter qualitative and quantitative differences in the macrofauna in the litter bags did not significantly affect decay rates of detritus. Laboratory studies revealed that the pH, bicarbonate concentration and aluminium content of the water particularly influenced the rate of decomposition of the pre-dried Juncus material. The extent of leaching and autolysis and the relative importance of fungi and bacteria in the decomposition of fresh Juncus leaves were studied using antifungal and antibacterial agents. In the laboratory leaching and autolysis accounted for 28–32% of the organic weight loss of coarse detritus. Leaching and autolysis caused the highest weight loss in the strongly acid medium. After 37 days of incubation in control media with pH 3.5 and 5.6 total organic weight loss was 55 and 59%, respectively. At pH 3.5 and 5.6 microbial decomposition accounted for organic weight losses of 23 and 31%, respectively. At low pH microbial decomposition was dominated by fungi, whereas, at pH 5.6 both fungi and bacteria played an important role in the breakdown processes. The contribution of macroinvertebrates to the breakdown of Juncus detritus seemed to be of minor importance.

For an investigation of chemical and physical properties of matter density can be a valuable expedient. Up to now methods for the determination of the density of solids, e.g. powders, generally give an accuracy not better than ±5‰ In this paper an apparatus is described allowing to determine the density of solids with an accuracy of at least ±0.2‰

In August 1952 one of the authors captured a series of rodents of the type Rattus rattus alexandrinus at Costermansville. The rats were examined at the Medical Laboratory, Astrida (Ruanda), by kind permission of the Director, Doctor J. B. Jadin. Two species of trombiculids were found in one ear, which was very scabby and contained other microscopic arachnidians.

The ICARUS collaboration operated the 760-ton T600 detector in a successful three-year physics run at the underground LNGS laboratories studying neutrino oscillations with the CNGS neutrino beam from CERN, and searching for atmospheric neutrino interactions. ICARUS performed a sensitive search for LSND-like anomalous νe appearance in the CNGS beam, which contributed to the constraints on the allowed parameters to a narrow region around Δm2=1 eV2, where all the experimental results can be coherently accommodated at 90% C.L. After a significant overhaul at CERN, the T600 detector has been installed at Fermilab. In 2020 cryogenic commissioning began with detector cool down, liquid Argon filling and recirculation. ICARUS has started operations and is presently in its commissioning phase with the aim of collecting its first neutrino events from the Booster Neutrino Beam and the NuMI off-axis beam. The main goal of the first year of ICARUS data taking will then be the definitive verification of the recent claim by NEUTRINO-4 short baseline reactor experiment both in the νμ channel with the BNB and in the νe with NuMI. After the first year of operations, ICARUS will commence its search for evidence of a sterile neutrino jointly with the SBND near detector, within the Short Baseline Neutrino (SBN) program. The ICARUS exposure to the NuMI beam will also give the possibility for other physics studies such as light dark matter searches and neutrino-Argon cross section measurements. The proposed contribution addresses ICARUS achievements, its status and plans for the new run at Fermilab and the ongoing developments of the analysis tools needed to fulfill its physics program.