Synthesis,antiproliferative and antibacterial activity of new amides of salinomycin

A series of 11 novel amides of salinomycin were synthesized for the first time. All the obtained compounds were found to show potent antiproliferative activity against human cancer cell lines including the drug-resistant cancer cells. Four new salinomycin derivatives revealed good antibacterial activity against clinical isolates of methicillin-resistant Staphylococcus epidermidis (MRSE).     

How to deal with oxygen radicals stemming from mitochondrial fatty acid oxidation

Oxygen radical formation in mitochondria is an incompletely understood attribute of eukaryotic cells. Recently, a kinetic model was proposed, in which the ratio between electrons entering the respiratory chain via FADH₂ or NADH determines radical formation. During glucose breakdown, the ratio is low; during fatty acid breakdown, the ratio is high (the ratio increasing—asymptotically—with fatty acid length to 0.5, when compared with 0.2 for glucose). Thus, fatty acid oxidation would generate higher levels of radical formation. As a result, breakdown of fatty acids, performed without generation of extra FADH₂ in mitochondria, could be beneficial for the cell, especially in the case of long and very long chained ones. This possibly has been a major factor in the evolution of peroxisomes. Increased radical formation, as proposed by the model, can also shed light on the lack of neuronal fatty acid oxidation and tells us about hurdles during early eukaryotic evolution. We specifically focus on extending and discussing the model in light of recent publications and findings.     

Anion inhibition study of the β-class carbonic anhydrase (PgiCAb) from the oral pathogen Porphyromonas gingivalis

The oral pathogenic bacterium Porphyromonas gingivalis, encodes for two carbonic anhydrase (CA, EC 4.2.1.1) one belonging to the β-class (PgiCAb) and another one to the γ-class (PgiCA). This last enzyme has been characterized earlier for its inhibition profile with various classes of CA inhibitors, such as the sulfonamides and anions, whereas for PgiCAb such data were not yet reported. Here we show that PgiCAb has a good catalytic activity for the CO₂ hydration reaction, with k_cat 2.8 × 10⁵ s⁻¹ and k_cat/K_m of 1.5 × 10⁷ M⁻¹ × s⁻¹, being inhibited by cyanate and diethyldithiocarbamate in the submillimolar range (K_Is of 0.23–0.76 mM) and more efficiently by sulfamide, sulfamate, phenylboronic acid and phenylarsonic acid (K_Is of 60–78 μM). The anion inhibition profile of the two P. gingivalis enzymes is very different. Identification of selective inhibitors of PgiCAb/PgiCA may lead to pharmacological tools useful for understanding the physiological role(s) of these enzymes, since this bacterium is the main causative agent of periodontitis and few treatment options are presently available.     

Responses of production and storage walnut pests to Bacillus thuringiensis insecticidal crystal protein fragments

Recent advances in genetic engineering have provided the opportunity to induce walnut plants to produce Bacillus thuringiensis Berliner insecticidal crystal protein fragments (ICPFs) for insect control. We studied the effects of two ICPFs CryIA(b) and CrylA(c) previously shown to be encoded by the cryIA(b) and cryIA(c) genes in the B. thuringiensis strains HD-1 and HD-73, respectively. The lethal effects on larvae of codling moth, Cydia pomonella (L.), navel orangeworm, Amyelois transitella (Walker), and the major postharvest pest Indianmeal moth, Plodia interpunctella (Hübner), were investigated. Both proteins were toxic to the three species tested. Indianmeal moth larvae were the most susceptible and navel orangeworm the least; CryIA(b) was generally more toxic to navel orangeworm. Similar relationships resulted when ICPFs were incorporated into the diet. Both ICPFs caused decreased rate of development of navel orangeworm. Effects on pupal weight occurred only at the highest concentration (100 ng/cm²). Neither ICPF affected frequency of mating or fecundity. In addition to the lethal effects, the extended development times observed could have considerable effects on the population dynamics of the navel orangeworm and possibly other species.     

A method to study zhizosphere processes in thin soil layers of different proximity to roots

Frankia is the diverse bacterial genus that fixes nitrogen within root nodules of actinorhizal trees and shrubs. Systematic and ecological studies of Frankia have been hindered by the lack of morphological, biochemical, or other markers to readily distinguish strains. Recently, nucleotide sequence of 16 S RNA from the small ribosomal subunit has been used to classify and identify a variety of microorganisms. We report nucleotide sequences from portions of the 16 S ribosomal RNA from Frankia strains AcnI1 isolated from Alnus viridis ssp. crispa (Ait.) Turrill and PtI1 isolated from Purshia tridentata (Pursh) DC. The number of nucleotide base substitutions and gaps we find more than doubles the previously reported sequence diversity for the same variable regions within other strains of Frankia.     

Effect of high temperatures and ash on germination of ten species from gorse shrubland

Seeds of ten species of Cistaceae, Ericaceae and Poaceae were examinated to compare their responses to high temperatures and ash, simulating the direct effect of fire on germination. A variable response to these factors between families and within species from the same family was detected.In Cistaceae, heat treatment pre-sowing stimulated germination. In Ericaceae, germination was stimulated by thermic shock, but a wide range of response was detected (between all four species), from Erica ciliari, very sensitive, to Daboecia cantabrica and Calluna vulgaris which showed no significant response. The range of reaction shown by the species of this family suggest that the size of the seeds is directly related to the difference in response, at least in species with a similar structure. In Poaceae, germination was not found to be dependent upon thermic shock.The effect of ash varies in magnitude. Although it decreased the germination percentage in all species, in Avenula marginata (Poaceae) the effect was not statistically significant, whilst in Ericaceae, particularly in those showing the highest levels of germination in the control (C. vulgaris and E. umbellata), the effect is to inhibit germination completely. In respect to the effect of ash the families could be arranged in the order Ericaceae>Cistaceae>Poaceae.Complex interactions between various dormancy types and seed size could explain these results. In species which depend on physical dormancy temperature has an important role. When other dormancy type is dominant in the control of germination, the medium characteristics could have a relevant role on seed response. In addition, the seed-size could determine the threshold of tolerance to temperature.     

Patch assessment in foraging flocks of European starlings: evidence for the use of public information

A field experiment was carried out to determine whether group-foragingstarlings (Sturnus vulgaris) use public information to helpthem estimate the quality of an artificial resource patch anddepart accordingly. Three kinds of information are potentiallyavailable in a group: patch-sample information, pre-harvestinformation, and public information. These three types of informationcan be combined into four patch assessment strategies: (1) patch-samplealone; (2) patch-sample and pre-harvest; (3) patch-sample andpublic; and (4) patch-sample, pre-harvest, and public. Dependingon the foraging environment we presented to the starlings, eachassessment strategy made a unique set of predictions concerningthe patch departure decisions of pairs of birds based on differencesin their foraging success. The environment was manipulated intwo ways: by altering the variability in patch quality and bychanging compatibility, the ease with which individual birdscould simultaneously acquire both patch-sample and public information.Our observations on patch persistence and departure order demonstratethat the starlings used a combination of patch-sample and publicinformation, but not pre-harvest information, to estimate thequality of the experimental patch. Moreover, our results suggestthat starlings use public information only when it is easilyavailable and ignore it under incompatible conditions. Thisstudy provides the first evidence of public information usein a patch assessment problem.     

Investigating structure and temporal scale in social organizations using identified individuals

Studies of individually identified animals can produce substantialdata sets containing information on the structure and temporalscale of social organizations. However, methods of analyzingsuch data are not well established. Important features of asocial organization are revealed by plotting the rate of persistenceof the associations between pairs of individuals over a rangeof time lags (lagged association rate). The consistency of long-termrelationships can be characterized using the rate of associationof pairs of individuals between their first and last observedassociations (intermediate association rate). A hierarchicalseries of models featuring exponentially decaying lagged associationrates may be fitted to these data. This technique retrievedthe essential parameters of five simulated social organizationsand, when used on real data, portrayed the essential featuresof the patterns of temporal change in relationships betweenanimals. The method should be especially useful for analyzingfissionfusion societies containing 10–10, 000 individuallyidentifiable animals.     

Cell penetrating peptide TAT can kill cancer cells via membrane disruption after attachment of camptothecin

Attachment of traditional anticancer drugs to cell penetrating peptides is an effective strategy to improve their application in cancer treatment. In this study, we designed and synthesized the conjugates TAT-CPT and TAT-2CPT by attaching camptothecin (CPT) to the N-terminus of the cell penetrating peptide TAT. Interestingly, we found that TAT-CPT and especially TAT-2CPT could kill cancer cells via membrane disruption, which is similar to antimicrobial peptides. This might be because that CPT could perform as a hydrophobic residue to increase the extent of membrane insertion of TAT and the stability of the pores. In addition, TAT-CPT and TAT-2CPT could also kill cancer cells by the released CPT after they entered cells. Taken together, attachment of CPT could turn cell penetrating peptide TAT into an antimicrobial peptide with a dual mechanism of anticancer action, which presents a new strategy to develop anticancer peptides based on cell penetrating peptides.     

WFS1 and non-syndromic low-frequency sensorineural hearing loss: A novel mutation in a Portuguese case

Low-frequency sensorineural hearing loss (LFSNHL) is an unusual type of HL in which frequencies at 2000 Hz and below are predominantly affected. Most of the families with LFSNHL carry missense mutations in WFS1 gene, coding for wolframin.