Antifungal Susceptibility, Exoenzyme Production and Cytotoxicity of Novel Oximes against Candida

Novel oximes were synthesized, their in vitro antifungal activity against Candida was evaluated and their cytotoxicity was determined. The procedure used for the synthesis of the oximes is aligned with the current green chemistry trend; water is employed as the solvent in this reaction. The minimum inhibitory and minimum fungicidal concentrations of the oximes were evaluated using the CLSI M27-A3 method. The influence of these compounds on the inhibition of the production of hydrolytic enzymes, phospholipase and proteinase by Candida was also investigated. The compounds showed a good ability to inhibit phospholipase, with a 50 % reduction in most cases. However, the tested compounds did not affect proteinase. The current results showed a substantial reduction in the phospholipase production, which suggests that compounds of this class may interfere with host infection and disease progression. The oximes examined showed lower fungicidal activities than fluconazole but interfered significantly with the expression of phospholipase. Some of the oximes included in this study could be a suitable matrix for the development of novel antifungal compounds.     

Analysis of Sharksucker, Echeneis naucrates, Induced Behavior Patterns in the Blacktip Shark, Carcharhinus limbatus

I analyzed and quantified the behavior of blacktip sharks, Carcharhinus limbatus, irritated by sharksuckers, Echeneis naucrates, attached to their bodies. The sharksucker induced behavior patterns were divided into simple rotational patterns, expressed by body turns along their main axes (roll, yaw, pitch); and complex patterns (wiggle, shake, wind, chafe), consisting of a combination or a repetition of simple behavior patterns. Three nonrotational behavior patterns were also observed (freeze, yawn, flicker). Of the 78 blacktip sharks examined, 70 performed either a simple or a complex pattern, or a combination of the two types. Of the total 195 rotational behavior patterns observed, only three wind patterns, performed as chaffing, led to the dislocation of a sharksucker, implying that the shark's primary intention may not be to shake off the teleost, but to initiate a position change to a less sensitive part of its body. Three sharks showed behavior patterns resembling typical agonistic display patterns, but they were induced by sharksuckers, not triggered by the presence of humans.     

In vitro inhibition of nitrogen mustard efficacy by postincubation of treated cells in serum protein

Lettre-Ehrlich cells were loaded with sufficient HN2 to produce about a 98% cell kill. Postincubation of the HN2-loaded cells in PBS resulted in the loss of about 40% of their HN2 without changing the cytolytic effect, supporting the proposal that only bound drug was effective. Postincubation of the HN2-loaded cells in PBS which contained 2% bovine serum albumin or in cell-free mouse ascitic fluid (1.8% protein) resulted in the same relative cellular HN2 loss as well as a 79% decrease in the cell kill. The cytolytic effect of HN2 is believed to be dependent on the degree to which the drug crosslinks DNA in 2 sequential reactions. It seems likely that such crosslinking occurred in nearly all of the PBS-postincubated cells, as they were nearly all killed. By analogy, albumin postincubation apparently blocked the competition of such crosslinking.     

First data on resistance mechanisms of Varroa jacobsoni (OUD.) against tau-fluvalinate

In 1991, the first losses of efficacy of tau-fluvalinate against the honeybee ectoparasite Varroa jacobsoni Oud. were recorded in Sicily. Since then, diminished efficacy with available pyrethroid treatments has been encountered in many regions of Italy. The aim of this study was to investigate the type of resistance in V. jacobsoni to the pyrethroid tau-fluvalinate by focusing on metabolic resistance mechanisms (detoxication). After developing a suitable application method, two synergists were used: piperonyl butoxide (PBO), as an inhibitor of the microsomal monooxygenases of the cytochrome P450 complex and S,S,S-tributylphosphorotrithioate (DEF), which blocks esterases. A significant decrease in the LC₅₀ values of the susceptible and of the resistant mite strains after the application of PBO was observed. A slight decrease of the LC₅₀ values was also observed after the application of DEF. However, this decrease was not significant. These results indicate that the resistance of Varroa mites to tau-fluvalinate can partly be explained by an increased detoxication due to the monooxygenases in the P450 system, which is blocked by PBO. Esterases seems to play a negligible role. Whether glutathione-S-transferases are involved, is still unknown, but other mechanisms, such as the modification of the binding sites and/or reduced uptake might be involved as well.     

A Systematic Comparison of Mathematical Models for Inherent Measurement of Ciliary Length: How a Cell Can Measure Length and Volume

Cells control organelle size with great precision and accuracy to maintain optimal physiology, but the mechanisms by which they do so are largely unknown. Cilia and flagella are simple organelles in which a single measurement, length, can represent size. Maintenance of flagellar length requires an active transport process known as intraflagellar transport, and previous measurements suggest that a length-dependent feedback regulates intraflagellar transport. But the question remains: how is a length-dependent signal produced to regulate intraflagellar transport appropriately? Several conceptual models have been suggested, but testing these models quantitatively requires that they be cast in mathematical form. Here, we derive a set of mathematical models that represent the main broad classes of hypothetical size-control mechanisms currently under consideration. We use these models to predict the relation between length and intraflagellar transport, and then compare the predicted relations for each model with experimental data. We find that three models—an initial bolus formation model, an ion current model, and a diffusion-based model—show particularly good agreement with available experimental data. The initial bolus and ion current models give mathematically equivalent predictions for length control, but fluorescence recovery after photobleaching experiments rule out the initial bolus model, suggesting that either the ion current model or a diffusion-based model is more likely correct. The general biophysical principles of the ion current and diffusion-based models presented here to measure cilia and flagellar length can be generalized to measure any membrane-bound organelle volume, such as the nucleus and endoplasmic reticulum.