Adaptive significance of amylase polymorphism in Drosophila . XII. density‐ and frequency‐dependent selection at the Amy locus in Drosophila subobscura reared on media with different carbohydrate composition

Egg‐to‐adult viability is studied in the progeny of the flies of different genotypes according to S and F alleles of Amy locus of Drsophila subobscura . This component of fitness is observed in the single and mixed cultures with various frequencies of three genotypes (S/S, F/F and S/F) under conditions of low (LD) and high densities (HD) on three types of media with different carbohydrate composition. In such multifactorial experimental conditions, density‐ and frequency‐dependent selection on certain Amy genotypes was observed. Genotype frequencies and carbohydrate composition have significant effect on the viability of Amy genotypes. The significant intergenotypic differences exist, mostly at HD conditions. The heterozygous genotype S/F has generally lower viability which decreases with its increased frequencies, on all media at LD or HD. The results suggest a high level of complexity and interaction between these two types of balanced selection.     

Clostridium difficile DNA polymerase IIIC: basis for activity of antibacterial compounds

Based on the finding that aerobic Gram-positive antibacterials that inhibit DNA polymerase IIIC (pol IIIC) were potent inhibitors of the growth of anaerobic Clostridium difficile (CD) strains, we chose to clone and express the gene for pol IIIC from this organism. The properties of the recombinant enzyme are similar to those of related pol IIICs from Gram-positive aerobes, e.g. B. subtilis. Inhibitors of the CD enzyme also inhibited B. subtilis pol IIIC, and were competitive with respect to the cognate substrate 2'-deoxyguanosine 5'-triphosphate (dGTP). Significantly, several of these inhibitors of the CD pol IIIC had potent activity against the growth of CD clinical isolates in culture.     

Appropriateness in allergic respiratory diseases health care in Italy: definitions and organizational aspects

In a historical period in which sustainability of the National Health Service is mandatory because of the international economical situation, the limited available resources at national level and the tendency of passing from a “population medicine” model towards the concept of “individualized medicine”, the debate on appropriateness of medical and surgical procedures is of central importance. The choosing wisely campaign, started in United States in 2012 and then spread all over the world, tries to summarize which are the most inappropriate procedures for each medical and surgical speciality; as far as allergic respiratory diseases, the most relevant Italian societies and the American Academy defined the allergological procedures with the highest probability of inappropriateness. In Italy, a recent decree of the Ministry of Health defined a list of more than 200 procedures that will be considered as inappropriate in certain conditions; many of these procedures concern allergology, including allergic respiratory diseases. In this commentary we discuss the above mentioned decree and the concept of appropriateness in the field of allergic respiratory diseases, trying to figure out some practical considerations based on the current health resources available in the field of allergology in Italy.     

The Shepherds’ Tale: A Genome-Wide Study across 9 Dog Breeds Implicates Two Loci in the Regulation of Fructosamine Serum Concentration in Belgian Shepherds

Diabetes mellitus is a serious health problem in both dogs and humans. Certain dog breeds show high prevalence of the disease, whereas other breeds are at low risk. Fructosamine and glycated haemoglobin (HbA1c) are two major biomarkers of glycaemia, where serum concentrations reflect glucose turnover over the past few weeks to months. In this study, we searched for genetic factors influencing variation in serum fructosamine concentration in healthy dogs using data from nine dog breeds. Considering all breeds together, we did not find any genome-wide significant associations to fructosamine serum concentration. However, by performing breed-specific analyses we revealed an association on chromosome 3 (p_corrected ≈ 1:68 × 10^-6) in Belgian shepherd dogs of the Malinois subtype. The associated region and its close neighbourhood harbours interesting candidate genes such as LETM1 and GAPDH that are important in glucose metabolism and have previously been implicated in the aetiology of diabetes mellitus. To further explore the genetics of this breed specificity, we screened the genome for reduced heterozygosity stretches private to the Belgian shepherd breed. This revealed a region with reduced heterozygosity that shows a statistically significant interaction (p = 0.025) with the association region on chromosome 3. This region also harbours some interesting candidate genes and regulatory regions but the exact mechanisms underlying the interaction are still unknown. Nevertheless, this finding provides a plausible explanation for breed-specific genetic effects for complex traits in dogs. Shepherd breeds are at low risk of developing diabetes mellitus. The findings in Belgian shepherds could be connected to a protective mechanism against the disease. Further insight into the regulation of glucose metabolism could improve diagnostic and therapeutic methods for diabetes mellitus.     

Making Large-Scale Networks from fMRI Data

Pairwise correlations are currently a popular way to estimate a large-scale network (> 1000 nodes) from functional magnetic resonance imaging data. However, this approach generally results in a poor representation of the true underlying network. The reason is that pairwise correlations cannot distinguish between direct and indirect connectivity. As a result, pairwise correlation networks can lead to fallacious conclusions; for example, one may conclude that a network is a small-world when it is not. In a simulation study and an application to resting-state fMRI data, we compare the performance of pairwise correlations in large-scale networks (2000 nodes) against three other methods that are designed to filter out indirect connections. Recovery methods are evaluated in four simulated network topologies (small world or not, scale-free or not) in scenarios where the number of observations is very small compared to the number of nodes. Simulations clearly show that pairwise correlation networks are fragmented into separate unconnected components with excessive connectedness within components. This often leads to erroneous estimates of network metrics, like small-world structures or low betweenness centrality, and produces too many low-degree nodes. We conclude that using partial correlations, informed by a sparseness penalty, results in more accurate networks and corresponding metrics than pairwise correlation networks. However, even with these methods, the presence of hubs in the generating network can be problematic if the number of observations is too small. Additionally, we show for resting-state fMRI that partial correlations are more robust than correlations to different parcellation sets and to different lengths of time-series.     

First occurrence of Paramphistomum microbothrium (Fischoeder 1901) in roe deer (Capreolus capreolus) in Serbia

Paramphistomum parasites identified by histology as Paramphistomum microbothrium were found in 18 of 34 roe deer (Capreolus capreolus) intestines from central Serbia, examined between 1998 and 2004. This represents the first record of P. microbothrium in roe deer in Serbia.     

Fluctuating vs. Continuous Exposure to H2O2: The Effects on Mitochondrial Membrane Potential,Intracellular Calcium,and NF-κB in Astroglia

The effects of H₂O₂ are widely studied in cell cultures and other in vitro systems. However, such investigations are performed with the assumption that H₂O₂ concentration is constant, which may not properly reflect in vivo settings, particularly in redox-turbulent microenvironments such as mitochondria. Here we introduced and tested a novel concept of fluctuating oxidative stress. We treated C6 astroglial cells and primary astrocytes with H₂O₂, using three regimes of exposure – continuous, as well as fluctuating at low or high rate, and evaluated mitochondrial membrane potential and other parameters of mitochondrial activity – respiration, reducing capacity, and superoxide production, as well as intracellular ATP, intracellular calcium, and NF-κB activation. When compared to continuous exposure, fluctuating H₂O₂ induced a pronounced hyperpolarization in mitochondria, whereas the activity of electron transport chain appears not to be significantly affected. H₂O₂ provoked a decrease of ATP level and an increase of intracellular calcium concentration, independently of the regime of treatment. However, fluctuating H₂O₂ induced a specific pattern of large-amplitude fluctuations of calcium concentration. An impact on NF-κB activation was observed for high rate fluctuations, whereas continuous and low rate fluctuating oxidative stress did not provoke significant effects. Presented results outline the (patho)physiological relevance of redox fluctuations.