Resistance of Dynamin-related Protein 1 Oligomers to Disassembly Impairs Mitophagy,Resulting in Myocardial Inflammation and Heart Failure

We have reported previously that a missense mutation in the mitochondrial fission gene Dynamin-related protein 1 (Drp1) underlies the Python mouse model of monogenic dilated cardiomyopathy. The aim of this study was to investigate the consequences of the C452F mutation on Drp1 protein function and to define the cellular sequelae leading to heart failure in the Python monogenic dilated cardiomyopathy model. We found that the C452F mutation increased Drp1 GTPase activity. The mutation also conferred resistance to oligomer disassembly by guanine nucleotides and high ionic strength solutions. In a mouse embryonic fibroblast model, Drp1 C452F cells exhibited abnormal mitochondrial morphology and defective mitophagy. Mitochondria in C452F mouse embryonic fibroblasts were depolarized and had reduced calcium uptake with impaired ATP production by oxidative phosphorylation. In the Python heart, we found a corresponding progressive decline in oxidative phosphorylation with age and activation of sterile inflammation. As a corollary, enhancing autophagy by exposure to a prolonged low-protein diet improved cardiac function in Python mice. In conclusion, failure of Drp1 disassembly impairs mitophagy, leading to a downstream cascade of mitochondrial depolarization, aberrant calcium handling, impaired ATP synthesis, and activation of sterile myocardial inflammation, resulting in heart failure.     

Selection becomes visible: enforced sexual dimorphism caused by sexual selection in the weevil Rhopalapion longirostre (Olivier 1807) (Coleoptera: Curculionoidea: Brentidae)

Extremely divergent traits between males and females are often the result of different requirements and behaviours of the sexes and will evolve relatively rapidly under selection forces. Sexual dimorphism in Rhopalapion longirostre is predominately manifested in the length and structure of the rostrum. To estimate how sexual selection shapes mating success in this weevil we compared paired and unpaired individuals collected from three populations in Austria. The mating process in this species is complex and lengthy. Statistical analyses based on detailed observations of their mating behaviour revealed that matched pairs show functional affinities in body size. Females and males with larger elytra, as well as males with large overall body size, are favoured mating partners, while males that are too small have no mating success. This arrangement ensures copulation and consequently successful egg deposition. For efficient egg channel boring into the flower buds of the host plant, Alcea rosea, the extremely long female rostrum is a crucial tool. Natural selection promotes longer rostra in females whereas sexual selection favours the shorter rostra in males. The major evolutionary forces, natural and sexual selection, enhance the sexual dimorphism in this species. © 2015 The Linnean Society of London, Biological Journal of the Linnean Society, 2015, 115 , 38–47.     

Biliverdin modulates the expression of C5aR in response to endotoxin in part via mTOR signaling

Macrophages play a crucial role in the maintenance and resolution of inflammation and express a number of pro- and anti-inflammatory molecules in response to stressors. Among them, the complement receptor 5a (C5aR) plays an integral role in the development of inflammatory disorders. Biliverdin and bilirubin, products of heme catabolism, exert anti-inflammatory effects and inhibit complement activation. Here, we define the effects of biliverdin on C5aR expression in macrophages and the roles of Akt and mammalian target of rapamycin (mTOR) in these responses. Biliverdin administration inhibited lipopolysaccharide (LPS)-induced C5aR expression (without altering basal expression), an effect partially blocked by rapamycin, an inhibitor of mTOR signaling. Biliverdin also reduced LPS-dependent expression of the pro-inflammatory cytokines TNF-α and IL-6. Collectively, these data indicate that biliverdin regulates LPS-mediated expression of C5aR via the mTOR pathway, revealing an additional mechanism underlying biliverdin’s anti-inflammatory effects.     

Regulatory system for the G1‐arrest during neuronal development in Drosophila

Neuronal network consists of many types of neuron and glial cells. This diversity is guaranteed by the constant cell proliferation of neuronal stem cells following stop cell cycle re‐entry, which leads to differentiation during development. Neuronal differentiation occurs mainly at the specific cell cycle phase, the G1 phase. Therefore, cell cycle exit at the G1 phase is quite an important issue in understanding the process of neuronal cell development. Recent studies have revealed that aberrant S phase re‐entry from the G1 phase often links cellular survival. In this review we discuss the different types of G1 arrest on the process of neuronal development in Drosophila. We also describe the issue that aberrant S phase entry often causes apoptosis, and the same mechanism might contribute to sensory organ defects, such as deafness.     

The Third Replicon of Members of the Burkholderia cepacia Complex,Plasmid pC3, Plays a Role in Stress Tolerance

The metabolically versatile Burkholderia cepacia complex (Bcc) occupies a variety of niches, including the plant rhizosphere and the cystic fibrosis lung (where it is often fatal to the patient). Bcc members have multipartite genomes, of which the third replicon, pC3 (previously chromosome 3), has been shown to be a nonessential megaplasmid which confers virulence and both antifungal and proteolytic activity on several strains. In this study, pC3 curing was extended to cover strains of 16 of the 17 members of the Bcc, and the phenotypes conferred by pC3 were determined. B. cenocepacia strains H111, MCO-3, and HI2424 were previously cured of pC3; however, this had not proved possible in the epidemic strain K56-2. Here, we investigated the mechanism of this unexpected stability and found that efficient toxin-antitoxin systems are responsible for maintaining pC3 of strain K56-2. Identification of these systems allowed neutralization of the toxins and the subsequent deletion of K56-2pC3. The cured strain was found to exhibit reduced antifungal activity and was attenuated in both the zebrafish and the Caenorhabditis elegans model of infection. We used a PCR screening method to examine the prevalence of pC3 within 110 Bcc isolates and found that this replicon was absent in only four cases, suggesting evolutionary fixation. It is shown that plasmid pC3 increases the resistance of B. cenocepacia H111 to various stresses (oxidative, osmotic, high-temperature, and chlorhexidine-induced stresses), explaining the prevalence of this replicon within the Bcc.     

BDKRB2 GENE -9/+9 POLYMORPHISM AND SWIMMING PERFORMANCE

The aim of the study was to evaluate the association between swimming performance and the -9/+9 (rs5810761) polymorphism within the BDKRB2 gene in successful competitive swimmers. Best individual swimming results expressed in FINA points achieved at short, middle and long distance events of 157 well-trained Polish swimmers were incorporated into an analysis. Athletes’ genotype and allele distributions were analysed in comparison to 230 unrelated sedentary subjects who served as controls with the χ² test. All samples were genotyped for the BDKRB2 -9/+9 polymorphism using the polymerase chain reaction (PCR). The effects of genotype on swimming performance were analysed with two-way (3 x 2; genotype x gender) analysis of variance with metrical age as a covariate for each distance specialization. No statistical differences in the genotype and allele frequencies were found in long distance swimmers when compared with the total group of swimmers or controls. The BDKRB2 +9/-9 genotype had no significant effect on swimming performance at short, middle or long distance, regardless of gender. The results of this study do not support the hypothesis that the BDKRB2 -9/+9 polymorphism is associated with swimming performance in Polish swimmers.