Contribution of Red Blood Cells and Platelets to Blood Clot Computed Tomography Imaging and Compressive Mechanical Characteristics

Thrombus computed tomography (CT) imaging characteristics may correspond with thrombus mechanical properties and thus predict thrombectomy success. The impact of red blood cell (RBC) content on these properties (imaging and mechanics) has been widely studied. However, the additional effect of platelets has not been considered. The objective of the current study was to examine the individual and combined effects of blood clot RBC and platelet content on resultant CT imaging and mechanical characteristics. Human blood clot analogues were prepared from a combination of preselected RBC volumes and platelet concentrations to decouple their contributions. The resulting clot RBC content (%) and platelet content (%) were determined using Martius Scarlet Blue and CD42b staining, respectively. Non-contrast and contrast-enhanced CT (NCCT and CECT) scans were performed to measure the clot densities. CECT density increase was taken as a proxy for clinical perviousness. Unconfined compressive mechanics were analysed by performing 10 cycles of 80% strain. RBC content is the major determinant of clot NCCT density. However, additional consideration of the platelet content improves the association. CECT density increase is influenced by clot platelet and not RBC content. Platelet content is the dominant component driving clot stiffness, especially at high strains. Both RBC and platelet content contribute to the clot's viscoelastic and plastic compressive properties. The current in vitro results suggest that CT density is reflective of RBC content and subsequent clot viscoelasticity and plasticity, and that perviousness reflects the clot's platelet content and subsequent stiffness. However, these indications should be confirmed in a clinical stroke cohort

Single-cell analysis of peptide expression and electrophysiology of right parietal neurons involved in male copulation behavior of a simultaneous hermaphrodite

Male copulation is a complex behavior that requires coordinated communication between the nervous system and the peripheral reproductive organs involved in mating. In hermaphroditic animals, such as the freshwater snail Lymnaea stagnalis, this complexity increases since the animal can behave both as male and female. The performance of the sexual role as a male is coordinated via a neuronal communication regulated by many peptidergic neurons, clustered in the cerebral and pedal ganglia and dispersed in the pleural and parietal ganglia. By combining single-cell matrix-assisted laser mass spectrometry with retrograde staining and electrophysiology, we analyzed neuropeptide expression of single neurons of the right parietal ganglion and their axonal projections into the penial nerve. Based on the neuropeptide profile of these neurons, we were able to reconstruct a chemical map of the right parietal ganglion revealing a striking correlation with the earlier electrophysiological and neuroanatomical studies. Neurons can be divided into two main groups: (i) neurons that express heptapeptides and (ii) neurons that do not. The neuronal projection of the different neurons into the penial nerve reveals a pattern where (spontaneous) activity is related to branching pattern. This heterogeneity in both neurochemical anatomy and branching pattern of the parietal neurons reflects the complexity of the peptidergic neurotransmission involved in the regulation of male mating behavior in this simultaneous hermaphrodite

Virulence Associated Gene 8 of Bordetella pertussis Enhances Contact System Activity by Inhibiting the Regulatory Function of Complement Regulator C1 Inhibitor.

Bordetella pertussis is a Gram-negative bacterium and the causative agent of whooping cough. Whooping cough is currently re-emerging worldwide and, therefore, still poses a continuous global health threat. B. pertussis expresses several virulence factors that play a role in evading the human immune response. One of these virulence factors is virulence associated gene 8 (Vag8). Vag8 is a complement evasion molecule that mediates its effects by binding to the complement regulator C1 inhibitor (C1-INH). This regulatory protein is a fluid phase serine protease that controls proenzyme activation and enzyme activity of not only the complement system but also the contact system. Activation of the contact system results in the generation of bradykinin, a pro-inflammatory peptide. Here, the activation of the contact system by B. pertussis was explored. We demonstrate that recombinant as well as endogenous Vag8 enhanced contact system activity by binding C1-INH and attenuating its inhibitory function. Moreover, we show that B. pertussis itself is able to activate the contact system. This activation was dependent on Vag8 production as a Vag8 knockout B. pertussis strain was unable to activate the contact system. These findings show a previously overlooked interaction between the contact system and the respiratory pathogen B. pertussis. Activation of the contact system by B. pertussis may contribute to its pathogenicity and virulence

Optimized Trigger for Ultra-High-Energy Cosmic-Ray and Neutrino Observations with the Low Frequency Radio Array

When an ultra-high energy neutrino or cosmic ray strikes the Lunar surface a radio-frequency pulse is emitted. We plan to use the LOFAR radio telescope to detect these pulses. In this work we propose an efficient trigger implementation for LOFAR optimized for the observation of short radio pulses.Comment: Submitted to Nuclear Instruments and Methods in Physics Research Section

ADAMTS-13 and bleeding phenotype in von Willebrand disease

Background: The bleeding phenotype of von Willebrand disease (VWD) varies highly between patients and can only partly be explained by von Willebrand factor (VWF) parameters. By cleaving large VWF multimers into smaller, less active multimers, ADAMTS-13 is an important regulator of VWF activity. However, it is unknown what the role of ADAMTS-13 is in individuals with VWD. Objectives: We therefore studied how ADAMTS-13 activity is associated with the laboratory and bleeding phenotype in individuals with VWD. Methods: We measured ADAMTS-13 activity using the fluorescence resonance energy transfer substrate VWF 73 assay in 638 individuals with VWD in the nationwide cross-sectional Willebrand in the Netherlands study and in 36 healthy controls. The bleeding phenotype was assessed using the Tosetto bleeding score. Results: ADAMTS-13 activity was similar in individuals with VWD (109% +/- 20.6%) and controls (110% +/- 19.7%). ADAMTS-13 activity was higher in individuals with VWD with type 3 than those with type 1 (mean difference, 11.8%; 95% confidence interval [CI], 2.9%-20.8%) or type 2 (mean difference, 16.1%; 95% CI, 7.1%-25.1%). ADAMTS-13 activity was not associated with the Tosetto bleeding score (0.1 Tosetto bleeding score increase per 10% ADAMTS-13 increase, 95% CI, -0.2 to 0.3). Furthermore, ADAMTS-13 activity did not differ between individuals with and without a bleeding event during the year preceding blood sampling (mean difference, 1.4%; 95% CI, -2.1% to 4.9%). Conclusion: ADAMTS-13 activity was highest in individuals with type 3 VWD, but it had only minor associations with VWF parameters. ADAMTS-13 activity does not influence the bleeding phenotype in individuals with VWD

Imaging Jupiter's radiation belts down to 127 MHz with LOFAR

Context. Observing Jupiter's synchrotron emission from the Earth remains today the sole method to scrutinize the distribution and dynamical behavior of the ultra energetic electrons magnetically trapped around the planet (because in-situ particle data are limited in the inner magnetosphere). Aims. We perform the first resolved and low-frequency imaging of the synchrotron emission with LOFAR at 127 MHz. The radiation comes from low energy electrons (~1-30 MeV) which map a broad region of Jupiter's inner magnetosphere. Methods (see article for complete abstract) Results. The first resolved images of Jupiter's radiation belts at 127-172 MHz are obtained along with total integrated flux densities. They are compared with previous observations at higher frequencies and show a larger extent of the synchrotron emission source (>=4 $R_J$). The asymmetry and the dynamic of east-west emission peaks are measured and the presence of a hot spot at lambda_III=230 {\deg} $\pm$ 25 {\deg}. Spectral flux density measurements are on the low side of previous (unresolved) ones, suggesting a low-frequency turnover and/or time variations of the emission spectrum. Conclusions. LOFAR is a powerful and flexible planetary imager. The observations at 127 MHz depict an extended emission up to ~4-5 planetary radii. The similarities with high frequency results reinforce the conclusion that: i) the magnetic field morphology primarily shapes the brightness distribution of the emission and ii) the radiating electrons are likely radially and latitudinally distributed inside about 2 $R_J$. Nonetheless, the larger extent of the brightness combined with the overall lower flux density, yields new information on Jupiter's electron distribution, that may shed light on the origin and mode of transport of these particles.Comment: 10 pages, 12 figures, accepted for publication in A&A (27/11/2015) - abstract edited because of limited character

Differences in Nevirapine Biotransformation as a Factor for its Sex-Dependent Dimorphic Profile of Adverse Drug Reactions

OBJECTIVES: Nevirapine is widely used for the treatment of HIV-1 infection; however, its chronic use has been associated with severe liver and skin toxicity. Women are at increased risk for these toxic events, but the reasons for the sex-related differences are unclear. Disparities in the biotransformation of nevirapine and the generation of toxic metabolites between men and women might be the underlying cause. The present work aimed to explore sex differences in nevirapine biotransformation as a potential factor in nevirapine-induced toxicity. METHODS: All included subjects were adults who had been receiving 400 mg of nevirapine once daily for at least 1 month. Blood samples were collected and the levels of nevirapine and its phase I metabolites were quantified by HPLC. Anthropometric and clinical data, and nevirapine metabolite profiles, were assessed for sex-related differences. RESULTS: A total of 52 patients were included (63% were men). Body weight was lower in women (P = 0.028) and female sex was associated with higher alkaline phosphatase (P = 0.036) and lactate dehydrogenase (P = 0.037) levels. The plasma concentrations of nevirapine (P = 0.030) and the metabolite 3-hydroxy-nevirapine (P = 0.035), as well as the proportions of the metabolites 12-hydroxy-nevirapine (P = 0.037) and 3-hydroxy-nevirapine (P = 0.001), were higher in women, when adjusted for body weight. CONCLUSIONS: There was a sex-dependent variation in nevirapine biotransformation, particularly in the generation of the 12-hydroxy-nevirapine and 3-hydroxy-nevirapine metabolites. These data are consistent with the sex-dependent formation of toxic reactive metabolites, which may contribute to the sex-dependent dimorphic profile of nevirapine toxicity