Radiosensitizing and damaging effects of hyperthermia on different biological systems. Ehrlich ascites carcinoma cells

The cytotoxic and radiosensitizing effects of hyperthermia was shown on Ehrlich ascites tumor cells heated in vitro. The effect of hyperthermia resulted in the formation of local lesions in membranes of dying cells.     

Parallel dose-response curves in combination experiments

A possible experimental design for combination experiments is to compare the doseresponse curve of a single agent with the corresponding curve of the same agent using either a fixed amount of a second one or a fixed dose ratio. No interaction is then often defined by a parallel shift of these curves. We have performed a systematic study for various types of doseresponse relations both for the dose-additivity (Loewe additivity) and for the independence (Bliss independence) criteria for defining zero interaction. Parallelism between doseresponse curves of a single agent and those of the same agent in the presence of a fixed amount of another one is found for the Loewe-additivity criterion for linear doseresponse relations. For nonlinear relations, one has to differentiate between effect parallelism (parallel shift on the effect scale) and dose parallelism (parallel shift on the dose scale). In the case of Loewe additivity, zero-interaction dose parallelism is found for power, Weibull, median-effect and logistic doseresponse relations, given that special parameter relationships are fulfilled. The mechanistic model of competitive interaction exhibits dose parallelism but not effect parallelism for Loewe additivity. Bliss independence and Loewe additivity lead to identical results for exponential doseresponse curves. This is the only case for which dose parallelism was found for Bliss independence. Parallelism between single-agent doseresponse relations and Loewe additivity mixture relations is found for examples with a fixed doseratio design. However, this is again not a general property of the design adopted but holds only if special conditions are fulfilled. The comparison of combination doseresponse curves with single-agent relations has to be performed taking into account both potency and shape parameters. The results of this analysis lead to the conclusion that parallelism between zero interaction combination and single-agent doseresponse relations is found only for special cases and cannot be used as a general criterion for defining zero-interaction in combined-action assessment even if the correct potency shift is taken into account.     

Why do antioxidants fail to provide clinical benefit?

The results of recent randomized trials to test the influence of antioxidants on coronary-event rates and prognosis in patients with coronary-artery disease were disappointing. In none of these studies did the use of vitamin E improve prognosis. In contrast, treatment of coronary-artery disease with angiotensin-converting-enzyme (ACE) inhibitors reduced coronary-event rates and improved prognosis. ACE inhibition prevents the formation of angiotensin II, which has been shown to be a potent stimulus of superoxide-producing enzymes in atherosclerosis. The findings suggest that inhibition of superoxide production at enzymatic levels, rather than symptomatic superoxide scavenging, may be the better choice of treatment.     

Membrane microheterogeneity: Förster resonance energy transfer characterization of lateral membrane domains

Lateral membrane heterogeneity, in the form of lipid rafts and microdomains, is currently implicated in cell processes including signal transduction, endocytosis, and cholesterol trafficking. Various biophysical techniques have been used to detect and characterize lateral membrane domains. Among these, Förster resonance energy transfer (FRET) has the crucial advantage of being sensitive to domain sizes smaller than 50-100 nm, below the resolution of optical microscopy but, apparently, similar to those of rafts in cell membranes. In the last decade, several formalisms for the analysis of FRET in heterogeneous membrane systems have been derived and applied to the study of microdomains. They are critically described and illustrated here.     

Water and ions in a high resolution structure of B-DNA.

A detailed picture of hydration and counterion location in the B-DNA duplex d(GCGAATTCG) is presented. Detailed data have been obtained by single crystal x-ray diffraction at atomic resolution (0.89 A) in the presence of Mg(2+). The latter is the highest resolution ever obtained for a B-DNA oligonucleotide. Minor groove hydration is compared with that found in the Na(+) and Ca(2+) crystal forms of the related dodecamer d(CGCGAATTCGCG). High resolution data (1.45 A) of the Ca(2+) form obtained in our laboratory are used for that purpose. The central GAATTC has a very stable hydration spine identical in all cases, independent of duplex length and crystallization conditions (counterions, space group). However, the organization of the water molecules (tertiary and quaternary layers) associated with the central spine vary in each case.     

Detection of genetic variants affecting cattle behaviour and their impact on milk production: a genome‐wide association study

Behaviour traits of cattle have been reported to affect important production traits, such as meat quality and milk performance as well as reproduction and health. Genetic predisposition is, together with environmental stimuli, undoubtedly involved in the development of behaviour phenotypes. Underlying molecular mechanisms affecting behaviour in general and behaviour and productions traits in particular still have to be studied in detail. Therefore, we performed a genome‐wide association study in an F₂ Charolais × German Holstein cross‐breed population to identify genetic variants that affect behaviour‐related traits assessed in an open‐field and novel‐object test and analysed their putative impact on milk performance. Of 37 201 tested single nucleotide polymorphism (SNPs), four showed a genome‐wide and 37 a chromosome‐wide significant association with behaviour traits assessed in both tests. Nine of the SNPs that were associated with behaviour traits likewise showed a nominal significant association with milk performance traits. On chromosomes 14 and 29, six SNPs were identified to be associated with exploratory behaviour and inactivity during the novel‐object test as well as with milk yield traits. Least squares means for behaviour and milk performance traits for these SNPs revealed that genotypes associated with higher inactivity and less exploratory behaviour promote higher milk yields. Whether these results are due to molecular mechanisms simultaneously affecting behaviour and milk performance or due to a behaviour predisposition, which causes indirect effects on milk performance by influencing individual reactivity, needs further investigation.     

Dispersal vs. vicariance in the Mediterranean: historical biogeography of the Palearctic Pachydeminae (Coleoptera, Scarabaeoidea)

Aim The geological evolution of the Mediterranean region is largely the result of the Tertiary collision of the African and Eurasian Plates, but also a mosaic of migrating island arcs, fragmenting tectonic belts, and extending back‐arc basins. Such complex paleogeography has resulted in a ‘reticulate’ biogeographical history, in which Mediterranean biotas repeatedly fragmented and merged as dispersal barriers appeared and disappeared through time. In this study, dispersal‐vicariance analysis (DIVA) is used to assess the relative role played by dispersal and vicariance in shaping distribution patterns in the beetle subfamily Pachydeminae Reitter, 1902 (Scarabaeoidea), an example of east–west Mediterranean disjunction. Location The Mediterranean region, including North Africa, the western Mediterranean, Balkans–Anatolia, Middle East, Caucasus, the Iranian Plateau, and Central Asia. Methods A phylogenetic hypothesis of the Palearctic genera of Pachydeminae in conjunction with distributional data was analysed using DIVA. This method reconstructs the ancestral distribution in a given phylogeny based on the vicariance model, while allowing dispersal and extinction to occur. Unlike other methods, DIVA does not enforce area relationships to conform to a hierarchical ‘area cladogram’, so it can be used to reconstruct ‘reticulate’ biogeographical scenarios. Results Optimal reconstructions, requiring 23 dispersal events, suggest that the ancestor of Pachydeminae was originally present in the south‐east Mediterranean region. Basal splitting within the subfamily was caused by vicariance events related to the late Tertiary collision of the African microplates Apulia and Arabia with Eurasia, and the resultant arise of successive dispersal barriers (e.g. the Red Sea, the Zagros Mountains). Subsequent diversification in Pachydeminae involved multiple speciation events within the Middle East and Iran–Afghanistan regions, which gave rise to the least speciose genera of Pachydeminae (e.g. Otoclinius Brenske, 1896). Finally, the presence of Pachydeminae in the western Mediterranean region seems to be the result of a recent dispersal event. The ancestor of the Iberian genera Ceramida Baraud, 1987 and Elaphocera Gené, 1836 probably dispersed from the Middle East to the Iberian Peninsula across North Africa and the Gibraltar Strait during the ‘Messinian salinity crisis’ at the end of the Miocene. Main conclusions Although the basal diversification of Pachydeminae around the Mediterranean appears to be related to vicariance events linked to the geological formation of the Mediterranean Basin, dispersal has also played a very important role. Nearly 38% of the speciation events in the phylogeny resulted from dispersal to a new area followed by allopatric speciation between lineages. Relationships between western and eastern Mediterranean disjuncts are usually explained by dispersal through Central Europe. The biogeographical history of the Pachydeminae corroborates other biogeographical studies that consider North Africa to be an alternative dispersal route by which Mediterranean taxa could have achieved circum‐Mediterranean distributions.     

Functional role of phenylacetic acid from metapleural gland secretions in controlling fungal pathogens in evolutionarily derived leaf-cutting ants

Fungus-farming ant colonies vary four to five orders of magnitude in size. They employ compounds from actinomycete bacteria and exocrine glands as antimicrobial agents. Atta colonies have millions of ants and are particularly relevant for understanding hygienic strategies as they have abandoned their ancestors'' prime dependence on antibiotic-based biological control in favour of using metapleural gland (MG) chemical secretions. Atta MGs are unique in synthesizing large quantities of phenylacetic acid (PAA), a known but little investigated antimicrobial agent. We show that particularly the smallest workers greatly reduce germination rates of Escovopsis and Metarhizium spores after actively applying PAA to experimental infection targets in garden fragments and transferring the spores to the ants'' infrabuccal cavities. In vitro assays further indicated that Escovopsis strains isolated from evolutionarily derived leaf-cutting ants are less sensitive to PAA than strains from phylogenetically more basal fungus-farming ants, consistent with the dynamics of an evolutionary arms race between virulence and control for Escovopsis, but not Metarhizium. Atta ants form larger colonies with more extreme caste differentiation relative to other attines, in societies characterized by an almost complete absence of reproductive conflicts. We hypothesize that these changes are associated with unique evolutionary innovations in chemical pest management that appear robust against selection pressure for resistance by specialized mycopathogens.