Cyclooxygenase-2 dependent metabolism of 20-HETE increases adiposity and adipocyte enlargement in mesenchymal stem cell-derived adipocytes

20-Hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE), a product of the cytochrome P450 (CYP)-catalyzed ω-hydroxylation of arachidonic acid, induces oxidative stress and, in clinical studies, is associated with increased body mass index (BMI) and the metabolic syndrome. This study was designed to examine the effects of exogenous 20-HETE on mesenchymal stem cell (MSC)-derived adipocytes. The expression levels of CYP4A11 and CYP4F2 (major 20-HETE synthases in humans) in MSCs decreased during adipocyte differentiation; however, exogenous administration of 20-HETE (0.1–1 μM) increased adipogenesis in a dose-dependent manner in these cells (P < 0.05). The inability of a 20-HETE analog to reproduce these effects suggested the involvement of a metabolic product of 20-HETE in mediating its pro-adipogenic effects. A cyclooxygenase (COX)-1 selective inhibitor enhanced, whereas a COX-2 selective or a dual COX-1/2 inhibitor attenuated adipogenesis induced by 20-HETE. The COX-derived metabolite of 20-HETE, 20-OH-PGE₂, enhanced adipogenesis and lipid accumulation in MSCs. The pro-adipogenic effects of 20-HETE and 20-OH-PGE₂ resulted in the increased expression of the adipogenic regulators PPARγ and β-catenin in MSC-derived adipocytes. Taken together we show for the first time that 20-HETE-derived COX-2-dependent 20-OH-PGE₂ enhances mature inflamed adipocyte hypertrophy in MSC undergoing adipogenic differentiation.     

Alteration of Tropomyosin-binding Properties of Tropomodulin-1 Affects Its Capping Ability and Localization in Skeletal Myocytes

Tropomodulin (Tmod) is an actin-capping protein that binds to the two tropomyosins (TM) at the pointed end of the actin filament to prevent further actin polymerization and depolymerization. Therefore, understanding the role of Tmod is very important when studying actin filament dependent processes such as muscle contraction and intracellular transport. The capping ability of Tmod is highly influenced by TM and is 1000-fold greater in the presence of TM. There are four Tmod isoforms (Tmod1–4), three of which, Tmod1, Tmod3, and Tmod4, are expressed in skeletal muscles. The affinity of Tmod1 to skeletal striated TM (stTM) is higher than that of Tmod3 and Tmod4 to stTM. In this study, we tested mutations in the TM-binding sites of Tmod1, using circular dichroism (CD) and prediction analysis (PONDR). The mutations R11K, D12N, and Q144K were chosen because they decreased the affinity of Tmod1 to stTM, making it similar to that of affinity of Tmod3 and Tmod4 to stTM. Significant reduction of inhibition of actin pointed-end polymerization in the presence of stTM was shown for Tmod1 (R11K/D12N/Q144K) as compared with WT Tmod1. When GFP-Tmod1 and mutants were expressed in primary chicken skeletal myocytes, decreased assembly of Tmod1 mutants was revealed. This indicates a direct correlation between TM-binding and the actin-capping abilities of Tmod. Our data confirmed the hypothesis that assembly of Tmod at the pointed-end of the actin filament depends on its TM-binding affinity.     

Interspecific relationships in co‐occurring populations of social parasites and their host ants

Myrmica ant colonies host numerous insect species, including the larvae of Maculinea butterflies and Microdon myrmicae hoverflies. Little is known about the interspecific relationships among these social parasites and their host ants occurring in sympatric populations. We investigated communities of social parasites to assess the strategies allowing them to share the same pool of resources (i.e. Myrmica colonies). The present study was carried out at five sites inhabited by different social parasite communities, each comprising varying proportions of Maculinea teleius, Maculinea nausithous, Maculinea alcon, and Microdon myrmicae. We investigated their spatial distributions, host segregation, the degree of chemical similarity between social parasites and hosts, and temporal overlaps in colony resource exploitation. Spatial segregation among social parasites was found in two populations and it arises from microhabitat preferences and biological interactions. Local conditions can drive selection on one social parasite to use a Myrmica host species that is not exploited by other social parasites. Myrmica scabrinodis and Myrmica rubra nests infested by larvae of two social parasite species were found and the most common co‐occurrence was between Ma. teleius and Mi. myrmicae. The successful coexistence of these two species derives from their exploitation of the host colony resources at different times of the year. © 2013 The Linnean Society of London, Biological Journal of the Linnean Society, 2013, 109 , 699–709.     

Body size as an important factor determining trophic niche partitioning in three syntopic rhinolophid bat species

We investigated a community of syntopically occurring horseshoe bats (Rhinolophus hipposideros, R. euryale, R. ferrumequinum) in southern Slovakia. The faecal pellets of these bat species were collected in the field and later analysed under a dissecting microscope. The three species studied are known to be very similar as far as their ecology, echolocation and preferred habitats are concerned, but they diverge significantly in their body sizes. In this study, all three species fed predominantly on moths [59–80 percentage frequency (%f); 87–95 percentage volume (%vol)], but their diet compositions differed in the size of individuals consumed. The smallest bat species (R. hipposideros) fed only on the smallest moths (%f = 59; %vol = 87), the medium-sized species (R. euryale) mainly on medium-sized moths (%f = 60; %vol = 74) and the largest one (R. ferrumequinum) especially on the largest moths (%f = 54; %vol = 89). Despite similar preferred habitat and the main prey category, the rates of trophic niche overlap were surprisingly low. The trophic niche percentage overlap was 7–31% (computed from %f data) and 1–20% (computed from %vol data), respectively and suggests an extraordinary importance of mere divergences of bats in their body sizes for trophic niche partitioning and stable species coexistence.     

The retrograde response: when mitochondrial quality control is not enough

Mitochondria are responsible for generating adenosine triphosphate (ATP) and metabolic intermediates for biosynthesis. These dual functions require the activity of the electron transport chain in the mitochondrial inner membrane. The performance of these electron carriers is imperfect, resulting in release of damaging reactive oxygen species. Thus, continued mitochondrial activity requires maintenance. There are numerous means by which this quality control is ensured. Autophagy and selective mitophagy are among them. However, the cell inevitably must compensate for declining quality control by activating a variety of adaptations that entail the signaling of the presence of mitochondrial dysfunction to the nucleus. The best known of these is the retrograde response. This signaling pathway is triggered by the loss of mitochondrial membrane potential, which engages a series of signal transduction proteins, and it culminates in the induction of a broad array of nuclear target genes. One of the hallmarks of the retrograde response is its capacity to extend the replicative life span of the cell. The retrograde signaling pathway interacts with several other signaling pathways, such as target of rapamycin (TOR) and ceramide signaling. All of these pathways respond to stress, including metabolic stress. The retrograde response is also linked to both autophagy and mitophagy at the gene and protein activation levels. Another quality control mechanism involves age-asymmetry in the segregation of dysfunctional mitochondria. One of the processes that impinge on this age-asymmetry is related to biogenesis of the organelle. Altogether, it is apparent that mitochondrial quality control constitutes a complex network of processes, whose full understanding will require a systems approach. This article is part of a Special Issue entitled: Protein Import and Quality Control in Mitochondria and Plastids.     

Synthesis and biological activity of benzo-fused 7-deazaadenosine analogues. 5- and 6-substituted 4-amino- or 4-alkylpyrimido[4,5-b]indole ribonucleosides

Two series of new 4-aminopyrimido[4,5-b]indole ribonucleosides bearing phenyl or hetaryl group at position 5 or 6 have been prepared by Suzuki or Stille cross-coupling reactions employing X-Phos ligand with (het)arylboronic acids or stannanes. A series of 4-substituted nucleosides has been also prepared by Pd-catalyzed cross-couplings or nucleophilic substitution. Some of these compounds displayed moderate antiviral activities against HCV and dengue viruses.     

Climatic signals in tree-ring widths and wood structure of Pinus halepensis in contrasted environmental conditions

Tree-ring widths (RW), earlywood (EW) and latewood (LW) widths, the transition from early to latewood (T) and the occurrence of intra-annual density fluctuations in EW (E-ring) and in LW (L-ring), as well as the presence of resin canals in EW and LW, were analyzed in Aleppo pine (Pinus halepensis Mill.) from three sites in Spain and one in Slovenia to find out if the anatomical characteristics can provide additional seasonal climate–growth information from contrasted environmental conditions. Principal component analysis was applied to elucidate the relationship between the measured parameters and climate. Principal component factor PC1 proved to be related to parameters of EW and the climatic variables of winter-spring; PC2 to parameters of LW and climatic variables of summer–autumn; PC3 to conditions during transitions from humid to dry periods. The three PCs vary between sites and are determined by the climatic conditions during their formation. The study demonstrates that wood anatomical features may provide complementary information to that contained in tree-ring widths. Since such results are obtained on contrasting sites, it is likely that it may be generalized over the wide range of P. halepensis distribution representing a useful proxy for studies on a regional scale.     

Neuraminidase-Mediated,NKp46-Dependent Immune-Evasion Mechanism of Influenza Viruses

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