We examined the association between plasma antioxidant levels and markers of inflammation, including C-reactive protein (CRP) and fibrinogen (FG) in US adults. National Health and Nutrition Examination Survey participants examined between 2001 and 2002 were included, if data on CRP or FG levels. Serum vitamins A and E, two retinyl esters, and six carotenoids were measured using HPLC with photodiode array detection. Multivariable-adjusted linear regression analyses accounted for the survey design and sample weights. A total of 784 eligible participants were included; 47·5 % (n 372) were men. In multivariable linear regression models, serum α-carotene, trans-β-carotene, cis-β-carotene, β-cryptoxanthin, combined lutein/zeaxanthin, trans-lycopene, retinyl palmitate, α-tocopherol, retinol and 25-hydroxy vitamin D were negatively associated with serum CRP (P<0·001 for all comparisons). Serum α-carotene, trans-β-carotene, cis-β-carotene, combined lutein/zeaxanthin, trans-lycopene, α-tocopherol, retinol and 25-hydroxy vitamin D were negatively associated with serum FG levels (P<0·001 for all comparisons). In the same model, the risk of CVD, defined as CRP levels >3 mg/l, decreased with increasing levels of antioxidants (α-carotene, trans-β-carotene, cis-β-carotene, vitamins A and E). Furthermore, we found a moderate impact of adiposity on the link between antioxidants and CRP. Our results suggest that the lower the antioxidants levels, the higher the inflammatory burden, based on CRP and FG levels. Adiposity moderately affects this association. Furthermore, an inverse relationship between CVD risk and antioxidant levels was observed. This finding suggests that reduced levels of vitamins with antioxidant properties may predispose to increased CVD risk.

Introduction: Neuroticism is an important marker of vulnerability for both mental and physical disorders. Its link with multiple etiological pathways has been studied before. Inflammatory markers have been demonstrated to predict similar mental and physical disorders as neuroticism. However, currently no study has focused on the shared genetic background of neuroticism and inflammatory markers. In the present study we will focus on the phenotypic and genetic relationship between neuroticism and three commonly used inflammatory markers: C-reactive protein (CRP), fibrinogen and Immunoglobulin-G (IgG). Material and Methods: The study was conducted in 125 Dutch female twin pairs. For each participant, four different neuroticism scores were available to calculate a neuroticism composite score that was used in the statistical analyses. Blood samples for inflammatory marker determination were taken after an overnight fast. Heritabilities, phenotypic and genetic correlations were estimated using bivariate structural equation modeling. Results: Heritabilities are fair for neuroticism (0.55), CRP (0.52) and fibrinogen (0.67) and moderate for IgG (0.43). No significant phenotypic or genetic correlations were found between neuroticism and the inflammatory markers. Interaction models yielded no moderation of the genetic and environmental pathways in the regulation of inflammatory markers by neuroticism. Conclusion: Substantial heritabilities were observed for all variables. No evidence was found for significant shared (or moderation of) genetic or environmental pathways underlying neuroticism and inflammatory status.

In this study we examined the genetic architecture of variation in the pro-inflammatory state, using an extended twin-family design. Within the Netherlands Twin Register Biobank, fasting Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), C-Reactive Protein (CRP), and fibrinogen levels were available for 3,534 twins, 1,568 of their non-twin siblings, and 2,227 parents from 3,095 families. Heritability analyses took into account the effects of current and recent illness, anti-inflammatory medication, female sex hormone status, age, sex, body mass index, smoking status, month of data collection, and batch processing. Moderate broad-sense heritability was found for all inflammatory parameters (39%, 21%, 45%, and 46% for TNF-α, IL-6, CRP and fibrinogen, respectively). For all parameters, the remaining variance was explained by unique environmental influences and not by environment shared by family members. There was no resemblance between spouses for any of the inflammatory parameters, except for fibrinogen. Also, there was no evidence for twin-specific effects. A considerable part of genetic variation was explained by non-additive genetic effects for TNF-α, CRP, and fibrinogen. For IL-6, all genetic variance was additive. This study may have implications for future genome-wide association studies by setting a clear numerical target for genome-wide screens that aim to find genetic variants regulating the levels of these pro-inflammatory markers.

Nanoparticles composed of a magnetic iron oxide core surrounded by a metal shell have utility in a broad range of biomedical applications. However, the presence of surface energy differences between the two components makes wetting of oxide with metal unfavorable, precluding a “core–shell” structure of an oxide core completely surrounded by a thin metal shell. Three-dimensional island growth followed by island coalescence into thick shells is favored over the two-dimensional layer-by-layer growth of a thin, continuous metal coating of a true core–shell. Aqueous synthesis of gold-coated magnetite nanoparticles with analysis by infrared, energy-dispersive X-ray, and electron energy loss spectroscopies; high-resolution transmission electron microscopy; selected area electron diffraction; and high-angle annular dark-field scanning transmission electron microscopy showed two distinct morphologies that are inconsistent with an idealized core–shell. The majority were isolated ~16–22-nm-diameter nanoparticles consisting of ~7-nm-diameter magnetite and a thick deposition of gold, most often discontinuous, with some potentially “sandwiched” morphologies. A minority were aggregates of agglomerated magnetite decorated with gold but displaying significant bare magnetite. Both populations were successfully conjugated to fibrinogen and targeted to surface-activated platelets, demonstrating that iron oxide–gold nanoparticles produced by aqueous synthesis do not require an ideal core–shell structure for biological activity in cell labeling and targeting applications.

Although imperfect spatial localization in single-molecule object tracking experiments has long been recognized to induce apparent motion in an immobile population of molecules, this effect is often ignored or incorrectly analyzed for mobile molecules. In particular, apparent motion due to positional uncertainty is often incorrectly assigned as a distinct diffusive mode. Here we show that, due to both static and dynamic contributions, positional uncertainty does not introduce a new apparent diffusive mode into trajectories, but instead causes a systematic shift of each measured diffusion coefficient. This shift is relatively simple: a factor of σ2/Δt is added to each diffusion coefficient, where σ is the positional uncertainty length scale and Δt is the time interval between observations. Therefore, by calculating the apparent diffusion coefficients as a function of Δt, it is straightforward to separate the true diffusion coefficients from the effective positional uncertainty. As a concrete demonstration, we apply this approach to the diffusion of the protein fibrinogen adsorbed to a hydrophobic surface, a system that exhibits three distinct modes of diffusion.

The fate of a forming thrombus is determined through the delicate balance between the coagulation cascade, favouring clot formation, and the fibrinolytic system, favouring clot lysis. These processes occur simultaneously, and enhancement of fibrinolysis has been shown to reduce occlusive thrombus formation in animal models. This review examines the roles of the major fibrinolytic factors involved in clot lysis. The regulation of plasmin activity by plasminogen activators, α-2-antiplasmin, plasminogen activator inhibitor 1, and thrombin-activatable fibrinolysis inhibitor, and their effects on thrombus formation in vivo are discussed. Since alterations in fibrinolytic capacity appear to affect thrombus formation in animal models, there is considerable interest in the pharmacological manipulation of fibrinolysis.

Aqueous extracts of Schistosoma mansoni eggs have been shown to have fibrinolytic activity inhibitable by a serine protease inhibitor. Fibrinolytic activity was not present in extracts of either adult worms or cercariae. A 27 kDa enzyme that was proteolytically active on fibrinogen in zymography and that degraded fibrinogen in a pattern similar to that of plasmin, is presumed to be responsible for the schistosome egg fibrinolytic activity. Anti-human fibrinogen antisera were shown to have antibodies that cross-reacted with mouse fibrinogen in Western immunoblots. Electroblotted sera from S. mansoni-infected and control uninfected mice displayed different antigenic profiles when probed with the cross-reactive anti-human fibrinogen antibodies, suggesting an alteration in mouse host fibrinogen metabolism as a result of the parasitic infection. We discuss the possibility that modulation of fibrinogen metabolism is a factor in a recently discovered anti-atherogenic effect exerted by schistosomes.

The human fibrinogen γ-chain C-terminal segment functions as the platelet integrin binding site as well as the Factor XIIIa cross-linking substrate and thus plays an important role in blood clot formation and stabilization. The three-dimensional structure of this segment has been determined using carrier protein driven crystallization. The C-terminal segment, γ-(398–411), was attached to a linker sequence at the C-terminus of glutathione S-transferase and the structure of this fusion protein determined at 1.8 Å resolution. Functional studies of the chimeric protein demonstrate that the fibrinogen sequence in the presence of the carrier protein retains its specific functions as ligand for platelet integrin αIIb β3 (gpIIb/IIIa) and as a cross-linking substrate for Factor XIIIa. The structure obtained for the fibrinogen γ-chain segment is not affected by crystal packing and can provide the missing links to the recently reported model of cross-linked fibrin.