The rate of fusion of phospholipid vesicles and the role of bilayer curvature

Kinetics of Ca²⁺-induced fusion of phosphatidylserine vesicles is studiied for lipid concentrations varying from 1 μM to 100 μM. Fusion is monitored by mixing of aqueous vesicle contents and by explicitly accounting for leakage. The analysis provides separately rates of aggregation and fusion. The rate of fusion per se decreases steeply with vesicle size.     

Gender difference in C-reactive protein concentrations in individuals with atherothrombotic risk factors and apparently healthy ones.

Recent studies have shown that C-reactive proteins have a pathogenetic role in atherothrombosis and concentrations of these substances could be used as a marker for future vascular events. The objective of this study was to determine gender differences in highly sensitive C-reactive protein (hs-CRP) in individuals with atherothrombotic risk factors and apparently healthy ones. We have presently matched 469 females and 469 males having the same age and body mass index (BMI). Of these, 210 men and 210 women had no atherothrombotic risk factors. In this group the hs-CRP concentrations were 1.6+/-3.4 mg l(-1) in women and 1.0+/-2.7 mg l(-1) in men (p<0.0005). These values were 2.1+/-3.4 mg l(-1) and 1.5+/-2.8 mg l(-1), respectively, in the entire cohort (p<0.0005), which included also individuals with atherothrombotic risk factors. We conclude that significant gender differences exist in hs-CRP concentrations despite perfect matching for age and BMI. These differences should be reflected in guidelines that suggest hs-CRP cut-off points for the stratification of vascular risk.     

Feedback-Based,System-Level Properties of Vertebrate-Microbial Interactions

Background

Improved characterization of infectious disease dynamics is required. To that end, three-dimensional (3D) data analysis of feedback-like processes may be considered.

Methods

To detect infectious disease data patterns, a systems biology (SB) and evolutionary biology (EB) approach was evaluated, which utilizes leukocyte data structures designed to diminish data variability and enhance discrimination. Using data collected from one avian and two mammalian (human and bovine) species infected with viral, parasite, or bacterial agents (both sensitive and resistant to antimicrobials), four data structures were explored: (i) counts or percentages of a single leukocyte type, such as lymphocytes, neutrophils, or macrophages (the classic approach), and three levels of the SB/EB approach, which assessed (ii) 2D, (iii) 3D, and (iv) multi-dimensional (rotating 3D) host-microbial interactions.

Results

In all studies, no classic data structure discriminated disease-positive (D+, or observations in which a microbe was isolated) from disease-negative (D–, or microbial-negative) groups: D+ and D– data distributions overlapped. In contrast, multi-dimensional analysis of indicators designed to possess desirable features, such as a single line of observations, displayed a continuous, circular data structure, whose abrupt inflections facilitated partitioning into subsets statistically significantly different from one another. In all studies, the 3D, SB/EB approach distinguished three (steady, positive, and negative) feedback phases, in which D– data characterized the steady state phase, and D+ data were found in the positive and negative phases. In humans, spatial patterns revealed false-negative observations and three malaria-positive data classes. In both humans and bovines, methicillin-resistant Staphylococcus aureus (MRSA) infections were discriminated from non-MRSA infections.

Conclusions

More information can be extracted, from the same data, provided that data are structured, their 3D relationships are considered, and well-conserved (feedback-like) functions are estimated. Patterns emerging from such structures may distinguish well-conserved from recently developed host-microbial interactions. Applications include diagnosis, error detection, and modeling.     

Evaluating spatial constraints in cellular assembly processes using a Monte Carlo approach

Biomolecular behavior commonly involves complex sets of interacting components that are challenging to understand through solution-based chemical theories. Molecular assembly is especially intriguing in the cellular environment because of its links to cell structure in processes such as chemotaxis. We use a coarse-grained Monte Carlo simulation to elucidate the importance of spatial constraints in molecular assembly. We have performed a study of actin filament polymerization through this space-aware probabilistic lattice-based model. Quantitative results are compared with nonspatial models and show convergence over a wide parameter space, but marked divergence over realistic levels corresponding to macromolecular crowding inside cells and localized actin concentrations found at the leading edge during cell motility. These conclusions have direct implications for cell shape and structure, as well as tumor cell migration.     

Can the Red-Green Duochrome Test Be Used Prior to Correcting the Refractive Cylinder Component?

Purpose

A primary task of the eye care professional is determining the refraction, or optical correction, of a patient. The duochrome red-green test is a standard tool for verification of the final refraction. Traditionally, it is recommended for use both prior to and subsequent to determining the cylindrical or astigmatic component of the refraction. In order for it to be effective when used before correcting the cylinder it is necessary that the COLC (Circle of Least Confusion) be on the retina. This study examined whether it is necessarily true that the duochrome response in uncorrected astigmatism will be as trust-worthy as it is with corrected cylinders.

Methods

The red-green examination was performed monocularly under the following three conditions: a. fully corrected refraction for the subgroup of eyes that had spherical refractions and for the subgroup of eyes with sphero-cylindrical refractions. b. best sphere-only correction without cylinder correction in sphero-cylindrical eyes c. an induced cylinder error in spherical eyes. The interval between the last “red” response and the first “green” response for the right eyes as a group and separately for the physiological cylinder and induced cylinder correction sub-groups was calculated and compared using a paired, two-tailed t-test.

Results

The intervals between “red” and “green” responses were not significantly different in the population as a whole and in the uncorrected physiological cylinder and induced cylinder subgroups examined.

Conclusion

Based on the finding that the interval of red-green equality with fully corrected cylinder and without the cylindrical correction are not significantly different, the red-green duochrome test can indeed be used both before and after cylindrical correction.     

The role of 20-HETE in androgen-mediated hypertension

Androgen plays an important role in blood pressure regulation. Epidemiological studies have shown that men have a higher prevalence for developing hypertension than aged-matched, premenopausal women. Interestingly, postmenopausal women and women with polycystic ovary syndrome, both of which have increased endogenous androgen production, have elevated risks for hypertension suggesting that androgen may contribute to its development. Studies from our laboratory and others have provided substantial evidence that 20-hydroxyeicosatetraenoic acid (20-HETE) mediates the hypertension seen in rodents treated with androgen. 20-HETE is the cytochrome P450 (CYP)-derived ω-hydroxylated metabolite of arachidonic acid. 20-HETE plays a complex role in blood pressure regulation. In the kidney tubules, 20-HETE decreases blood pressure by promoting natriuresis, while in the microvasculature it has a pressor effect. In the microcirculation, 20-HETE participates in the regulation of vascular tone by sensitizing the smooth muscle cells to constrictor stimuli and contributes to myogenic, mitogenic and angiogenic responses. In addition, 20-HETE acts on the endothelium to promote endothelial dysfunction and endothelial activation. Recently, we have demonstrated that 20-HETE induces endothelial ACE thus setting forth a potential feed forward mechanism through activation of the renin-angiotensin-aldosterone system. In this review, we will discuss the pro-hypertensive effects of 20-HETE and its role in androgen-induced vascular dysfunction and hypertension.     

Oleic acid and adipokines synergize in inducing proliferation and inflammatory signalling in human vascular smooth muscle cells

In the context of obesity, perivascular fat produces various adipokines and releases free fatty acids, which may induce inflammation and proliferation in the vascular wall. In this study we investigated how adipokines, oleic acid (OA) and the combined treatment regulate human vascular smooth muscle cell (hVSMC) proliferation and migration and the underlying signalling pathways. Adipocyte‐conditioned media (CM) generated from human adipocytes induces a prominent proliferation and migration of hVSMC. Autocrine action of adiponectin totally abolishes CM‐induced proliferation. Furthermore, OA but not palmitic acid induces proliferation of hVSMC. CM itself does not contain fatty acids, but CM in combination with OA markedly enhances proliferation of hVSMC in a synergistic way. Both the nuclear factor (NF)‐κB and the mammalian target of rapamycin (mTOR) pathway were synergistically activated under these conditions and found to be essential for hVSMC proliferation. Expression of iNOS and production of nitric oxide was only enhanced by combined treatment inducing a marked release of VEGF. Combination of OA and VEGF induces an additive increase of hVSMC proliferation. We could show that the combination of CM and OA led to a synergistic proliferation of hVSMC. Expression of iNOS and production of nitric oxide were only enhanced under these conditions and were paralleled by a marked release of VEGF. These results suggest that the combined elevated release of fatty acids and adipokines by adipose tissue in obesity might be critically related to hVSMC dysfunction, vascular inflammation and the development of atherosclerosis.