Correction: Active microrheology determines scale-dependent material properties of Chaetopterus mucus.

[This corrects the article DOI: 10.1371/journal.pone.0176732.].

Active microrheology determines scale-dependent material properties of Chaetopterus mucus.

We characterize the lengthscale-dependent rheological properties of mucus from the ubiquitous Chaetopterus marine worm. We use optically trapped probes (2-10 µm) to induce microscopic strains and measure the stress response as a function of oscillation amplitude. Our results show that viscoelastic properties are highly dependent on strain scale (l), indicating three distinct lengthscale-dependent regimes at l1 ≤4 µm, l2≈4-10 µm, and l3≥10 µm. While mucus response is similar to water for l1, suggesting that probes rarely contact the mucus mesh, the response for l2 is distinctly more viscous and independent of probe size, indicative of continuum mechanics. Only for l3 does the response match the macroscopic elasticity, likely due to additional stiffer constraints that strongly resist probe displacement. Our results suggest that, rather than a single lengthscale governing crossover from viscous to elastic, mucus responds as a hierarchical network with a loose biopolymer mesh coupled to a larger scaffold responsible for macroscopic gel-like mechanics.

Malaria in South Africa: 110 years of learning to control the disease.

In Africa today, the drive towards controlling malaria is comparable with efforts made in the 1950s and 1960s during the World Health Organization's Global Malaria Eradication Campaign. Unlike the Eradication Campaign that 'covered' the globe but excluded Africa, the current endeavours focus on Africa, but not to the exclusion of the rest of the tropical and sub-tropical world. Major donor agencies are partnering with African governments in an attempt to curb transmission of malaria parasites, and in some countries on the edges of the distribution of malaria, there is talk of eliminating the disease. South Africa is at the very southernmost fringe of malaria distribution on the African continent and has a long history of intense malaria control activities. This article looks at what South Africa has achieved in the past and where it needs to go in the future, not only to maintain the status quo, but hopefully to eliminate transmission of the disease within its borders. 

Malaria vector control in South Africa.

Malaria vector control is primarily insecticide based and relies on indoor residual spraying (IRS) and the distribution of long-lasting insecticide-treated bednets (LLINs). These interventions have generally proved effective where appropriately implemented. However, the increasing incidence of insecticide resistance in target vector populations can, and in several cases already has, undermined the effectiveness of IRS and LLINs. Today there are very few localities on the African continent where populations of vector mosquitoes are still susceptible to the approved classes of insecticides. If elimination is to be achieved, SA needs to invest more resources into malaria control. 

Health promotion: from malaria control to elimination.

Here we reflect on the achievement of some of the diverse activities that have brought malaria under control, highlight key challenges and propose specific health promotion interventions required to move South Africa's malaria programme from control to elimination.

Comment on "Long-lived giant number fluctuations in a swarming granular nematic".

Narayan et al. (Reports, 6 July 2007, p. 105) reported giant number fluctuations attributed to curvature-driven active currents specific for nonequilibrium nematic systems. We present data demonstrating that similar results can be found in systems of spherical particles due either to inelastic clustering or persistent density inhomogeneity, suggesting two alternative explanations for their results.

Two-dimensional melting far from equilibrium in a granular monolayer.

We report an experimental investigation of the transition from a hexagonally ordered solid phase to a disordered liquid in a monolayer of vibrated spheres. The transition occurs as the intensity of the vibration amplitude is increased. Measurements of the density of dislocations and the positional and orientational correlation functions show evidence for a dislocation-mediated continuous transition from a solid phase with long-range order to a liquid with only short-range order. The results show a strong similarity to simulations of melting of hard disks in equilibrium, despite the fact that the granular monolayer is far from equilibrium due to the effects of interparticle dissipation and the vibrational forcing.

Generating controlled molecular gradients in 3D gels.

A new method for producing molecular gradients of arbitrary shape in thin three dimensional gels is described. Patterns are produced on the surface of the gel by printing with a micropump that dispenses small droplets of solution at controlled rates. The molecules in the solution rapidly diffuse into the gel and create a smooth concentration profile that is independent of depth. The pattern is relatively stable for long times, and its evolution can be accurately described by finite element modeling of the diffusion equation. As a demonstration of the method, direct measurements of protein gradients are performed by quantitative fluorescence microscopy. A complementary technique for measuring diffusion coefficients is also presented. This rapid, flexible, contactless approach to gradient generation is ideally suited for cell culture experiments to investigate the role of gradients of diffusible substances in processes such as chemotaxis, morphogenesis, and pattern formation, as well as for high-throughput screening of system responses to a wide range of chemical concentrations.

Preoperative evaluation for epilepsy surgery (Bonn Algorithm).

SUMMARY: Epilepsy surgery has been established as a successful treatment in patients with drug-resistant focal epilepsies. Different standardized surgical approaches were developed for resective or functional treatment. Successful surgical treatment, however, necessitates a careful presurgical evaluation. Although there are international standards for non invasive and invasive presurgical procedures most centers differ in their diagnostic strategy. This article gives a survey of the Bonn Epilepsy surgery program within which more than 1300 patients have been treated. After the method of patient selection different we describe tools of non invasive and invasive evaluation. This article serves only as a description of current practice in one center with a relatively large volume of cases. It presents just one opinion of a specific group within a wide spectrum of possible algorithms for presurgical evaluation that have briefly been outlined for 33 centers in Engels book [4].

Leukocyte adhesiveness/aggregation test (LAAT) to discriminate between viral and bacterial infections in children.

OBJECTIVES: We previously noted that white blood cells (WBC) have increased adhesive properties during bacterial infections. Here, we aim to explore the possibility of using the different adhesive properties of WBC as a means of differentiating between viral and bacterial infections, a common problem in paediatrics. METHODS: The adhesive properties of WBC in the peripheral blood of 25 children with documented bacterial infections, 15 with documented viral infections and 36 with probable viral infections, were studied by means of a leukocyte adhesiveness/aggregation slide test (LAAT). The results of the LAAT were compared with those of the other acute phase reactants, namely WBC, differential count and erythrocyte sedimentation rate (ESR), which were taken in the same blood sample in each patient. RESULTS: The sensitivity, specificity and positive predictive value were 92%, 96%, and 92%, respectively for the LAAT; 83%, 87% and 80% for the ESR; 56%, 78% and 56% for the white blood cell count; and 54%, 74% and 50% for the differential count. CONCLUSIONS: The presence of bacterial infections in children can be tested using a simple slide test to reveal the increased state of leukocyte adhesiveness/aggregation in the peripheral blood. The LAAT is a reliable, rapid and inexpensive test, and it can be a useful laboratory tool for the paediatrician treating a child with acute febrile illness.

Theoretical analysis of gradient detection by growth cones.

Gradients of diffusible and substrate-bound molecules play an important role in guiding axons to appropriate targets in the developing nervous system. Although some of the molecules involved have recently been identified, little is known about the physical mechanisms by which growth cones sense gradients. This article applies the seminal Berg and Purcell (1977) model of gradient sensing to this problem. The model provides estimates for the statistical fluctuations in the measurement of concentration by a small sensing device. By assuming that gradient detection consists of the comparison of concentrations at two spatially or temporally separated points, the model therefore provides an estimate for the steepness of gradient that can be detected as a function of physiological parameters. The model makes the following specific predictions. (a) It is more likely that growth cones use a spatial rather than temporal sensing strategy. (b) Growth cone sensitivity increases with the concentration of ligand, the speed of ligand diffusion, the size of the growth cone, and the time over which it averages the gradient signal. (c) The minimum detectable gradient steepness for growth cones is roughly in the range 1-10%. (d) This value varies depending on whether a bound or freely diffusing ligand is being sensed, and on whether the sensing occurs in three or two dimensions. The model also makes predictions concerning the role of filopodia in gradient detection.

Velocity distributions and density fluctuations in a granular gas.

Velocity distributions in a vibrated granular monolayer are investigated experimentally. Non-Gaussian velocity distributions are observed at low vibration amplitudes but cross over smoothly to Gaussian distributions as the amplitude is increased. Cross-correlations between fluctuations in density and temperature are present only when the velocity distributions are strongly non-Gaussian. Confining the expansion of the granular layer results in non-Gaussian velocity distributions that persist to high vibration amplitudes.

Thiol dependent isomerization of all-trans-retinoic acid to 9-cis-retinoic acid.

The important biological effector 9-cis-retinoic acid can be generated by liver microsomes or by bovine serum albumin in detergent. The mechanism of this isomerization reaction is the subject of these studies. The protein mediated isomerization process is shown to be thiol- and pH-dependent. Moreover, the retinoic acids are also isomerized by 1-dodecanethiol in the presence of detergents. This isomerization process is pH-dependent as well, with isomerization rates increasing with pH. The isomerization reactions are quenched with free radical traps, such as alpha-tocopherol and ascorbic acid, suggesting that a thiol radical mechanism, rather than a thiolate anion-dependent mechanism, is implicated here. The pH dependence can be understood in terms of a thiol radical mechanism, because thiol radicals are produced from thiolate anions in the presence of oxygen. The facile thiol-mediated isomerization of the retinoic acids suggests that this could be a physiologically relevant mechanism for the formation of 9-cis-retinoic acid from all-trans-retinoic acid.

Resident moonlighting: toward an equitable balance.

Extracurricular employment ("moonlighting") by resident physicians has been a subject of considerable controversy for many years. A review of the medical literature for the past two decades reveals substantial debate regarding the legitimacy of the practice, the establishment of some organizational policies, and the intrusion of some new legal concerns. I have summarized the findings of previous studies of the subject, including both general reviews and data-based studies. The latter suggest that escalating financial pressures, changing call schedules, and perceived shifts in career opportunities all contribute to continuation of the practice. In addition, some extracurricular jobs seem to offer valuable clinical opportunities. These factors, which have led to several fundamental dilemmas for academic medical programs, have been explicitly defined. There is still a need for a coherent, ethical, economically sensitive, and legally defensible policy on moonlighting. Using the tangible data about moonlighting and the ongoing controversies, I have synthesized some model guidelines that could be used by residency programs to place moonlighting activities on a fair and reasonable footing.

Isomerization of all-trans-retinoic acid to 9-cis-retinoic acid.

The discovery of the biological activity of 9-cis-retinoic acid raises questions as to its mode of biosynthesis. A simple mechanism involves the direct isomerization of all-trans-retinoic acid to 9-cis-retinoic acid. It is shown here that bovine liver membranes, but not supernatant fractions, can isomerize all-trans-retinoic acid into 9-cis-retinoic acid and 13-cis-retinoic acid. The concentration of 9-cis-retinoic acid generated approaches its equilibrium concentration, which is determined here to be approximately 15%. However, the isomerization process could not be shown to be saturable, and is first-order in all-trans-retinoic acid in the concentration range measured (8.3 nM to 3 microM). Isomerization reactions measured using bovine liver microsomes appear to be mediated by thiol groups, as they can be blocked by group-specific thiol-blocking reagents such as N-ethylmaleimide. It is interesting to note that the non-stereospecific behaviour observed here mimics what is observed when all-trans-retinoic acid is applied to cells. Finally, significant formation of 9-cis-retinoids was not found when the reaction was carried out with liver microsomes and either all-trans-retinol or all-trans-retinal.

In vitro exposure to mercury and cadmium alters term human placental membrane fluidity.

The effect of incubation with mercury (Hg) as HgCl2 and cadmium (Cd) as CdCl2, at levels of 6 or 12 micrograms/ml of medium, on explants of term human placental microvillus membrane fluidity were studied. After incubation for 6 or 24 hr explants for each dose level were pooled and washed with fresh medium to remove any unbound metal. Placental membranes were separated by differential centrifugation and fluidity was studied by steady-state fluorescence polarization, expressed as the fluorescence anisotropy, r, with 1,6-diphenyl-1,3,5-hexatriene as a probe. The results show that membranes derived from explants incubated for 24 hr with either 6 or 12 micrograms/ml medium of either metal showed fluorescence anisotropy values (i.e., decreased fluidity) significantly higher than that of their respective controls. With 6 micrograms/ml of either metal the decrease in fluidity was highly significant for both metals and with 12 micrograms/ml a further decrease in membrane fluidity was observed with either metal. Both metals accumulated in placental membranes in proportion to their level in the medium. Membrane accumulation of Cd was higher than that of Hg. The cholesterol, phospholipid, and cholesterol-to-phospholipid mole ratios in membranes derived from metal-treated explants were unchanged, compared to their respective controls. However, no changes in membrane fluidity were observed in the samples incubated for 6 hr. In conclusion, exposure of placental cells to Hg and Cd caused accumulation of the metals in the membranes and lowered the membrane fluidity, which may affect membrane function and cause damage to the developing fetus.

Enzyme activities in the term human placenta: in vitro effect of cadmium.

The effect of cadmium (Cd) as CdCl2 on some placental enzyme activities were studied after explants had been incubated with the salt for 6 or 24 hr. The results indicated that, for both incubation periods, Cd at low doses had a stimulatory effect on aryl hydrocarbon hydroxylase (AHH) (a phase I enzyme) and on quinone reductase and catecholamine-O-methyltransferase (COMT) (both phase II enzymes). This effect was dose- and time-dependent. Only the activities of AHH and COMT showed a biphasic response, (i.e., increases at the lower dose levels and decreases with the higher ones), whereas that of quinone reductase continually increased with all the dose levels of the metal administered. Glucose-6-phosphate dehydrogenase (G-6-PD) activity was found to be inhibited at all the dose levels of Cd tested, the effect also being time- and dose-dependent. In conclusion, it appears that the use of placental explants can serve as a valuable means for studying the toxic effects of certain xenobiotics, as reflected in the activity of various important enzymes.