Ecomorphology of the African felid ensemble: The role of the skull and postcranium in determining species segregation and assembling history

Morphology of extant felids is regarded as highly conservative. Most previous studies have focussed on skull morphology, so a vacuum exists about morphofunctional variation in postcranium and its role in structuring ensembles of felids in different continents. The African felid ensemble is particularly rich in ecologically specialized felids. We studied the ecomorphology of this ensemble using 31 cranial and 93 postcranial morphometric variables measured in 49 specimens of all 10 African species. We took a multivariate approach controlling for phylogeny, with and without body size correction. Postcranial and skull + postcranial analyses (but not skull‐only analyses) allowed for a complete segregation of species in morphospace. Morphofunctional factors segregating species included body size, bite force, zeugopodial lengths and osteological features related to parasagittal leg movement. A general gradient of bodily proportions was recovered: lightly built, long‐legged felids with small heads and weak bite forces vs. the opposite. Three loose groups were recognized: small terrestrial felids, mid‐to‐large sized scansorial felids and specialized Acinonyx jubatus and Leptailurus serval. As predicted from a previous study, the assembling of the African felid ensemble during the Plio‐Pleistocene occurred by the arrival of distinct felid lineages that occupied then vacant areas of morphospace, later diversifying in the continent.     

Hybridization and speciation

Hybridization has many and varied impacts on the process of speciation. Hybridization may slow or reverse differentiation by allowing gene flow and recombination. It may accelerate speciation via adaptive introgression or cause near‐instantaneous speciation by allopolyploidization. It may have multiple effects at different stages and in different spatial contexts within a single speciation event. We offer a perspective on the context and evolutionary significance of hybridization during speciation, highlighting issues of current interest and debate. In secondary contact zones, it is uncertain if barriers to gene flow will be strengthened or broken down due to recombination and gene flow. Theory and empirical evidence suggest the latter is more likely, except within and around strongly selected genomic regions. Hybridization may contribute to speciation through the formation of new hybrid taxa, whereas introgression of a few loci may promote adaptive divergence and so facilitate speciation. Gene regulatory networks, epigenetic effects and the evolution of selfish genetic material in the genome suggest that the Dobzhansky–Muller model of hybrid incompatibilities requires a broader interpretation. Finally, although the incidence of reinforcement remains uncertain, this and other interactions in areas of sympatry may have knock‐on effects on speciation both within and outside regions of hybridization.     

Quantifying the effects of migration and mutation on adaptation and demography in spatially heterogeneous environments

How do mutation and gene flow influence population persistence, niche expansion and local adaptation in spatially heterogeneous environments? In this article, we analyse a demographic and evolutionary model of adaptation to an environment containing two habitats in equal frequencies, and we bridge the gap between different theoretical frameworks. Qualitatively, our model yields four qualitative types of outcomes: (i) global extinction of the population, (ii) adaptation to one habitat only, but also adaptation to both habitats with, (iii) specialized phenotypes or (iv) with generalized phenotypes, and we determine the conditions under which each equilibrium is reached. We derive new analytical approximations for the local densities and the distributions of traits in each habitat under a migration–selection–mutation balance, compute the equilibrium values of the means, variances and asymmetries of the local distributions of phenotypes, and contrast the effects of migration and mutation on the evolutionary outcome. We then check our analytical results by solving our model numerically, and also assess their robustness in the presence of demographic stochasticity. Although increased migration results in a decrease in local adaptation, mutation in our model does not influence the values of the local mean traits. Yet, both migration and mutation can have dramatic effects on population size and even lead to metapopulation extinction when selection is strong. Niche expansion, the ability for the population to adapt to both habitats, can also be prevented by small migration rates and a reduced evolutionary potential characterized by rare mutation events of small effects; however, niche expansion is otherwise the most likely outcome. Although our results are derived under the assumption of clonal reproduction, we finally show and discuss the links between our model and previous quantitative genetics models.     

Decreased mitochondrial OGG1 expression is linked to mitochondrial defects and delayed hepatoma cell growth

Many solid tumor cells exhibit mitochondrial respiratory impairment; however, the mechanisms of such impairment in cancer development remain unclear. Here, we demonstrate that SNU human hepatoma cells with declined mitochondrial respiratory activity showed decreased expression of mitochondrial 8-oxoguanine DNA glycosylase/lyase (mtOGG1), a mitochondrial DNA repair enzyme; similar results were obtained with human hepatocellular carcinoma tissues. Among several OGG1-2 variants with a mitochondrial-targeting sequence (OGG1-2a, -2b, -2c, -2d, and -2e), OGG1-2a was the major mitochondrial isoform in all examined hepatoma cells. Interestingly, hepatoma cells with low mtOGG1 levels showed delayed cell growth and increased intracellular reactive oxygen species (ROS) levels. Knockdown of OGG1-2 isoforms in Chang-L cells, which have active mitochondrial respiration with high mtOGG1 levels, significantly decreased cellular respiration and cell growth, and increased intracellular ROS. Overexpression of OGG1-2a in SNU423 cells, which have low mtOGG1 levels, effectively recovered cellular respiration and cell growth activities, and decreased intracellular ROS. Taken together, our results suggest that mtOGG1 plays an important role in maintaining mitochondrial respiration, thereby contributing to cell growth of hepatoma cells.     

Three New Loxophyllum Species (Ciliophora: Pleurostomatida) from China with a Brief Review of the Marine and Brackish Loxophyllum Species

Recent studies indicate that there is a high diversity of pleurostomatid ciliates in the coastal waters of China. Here, three new congeners of Loxophyllum, L. caudatum sp. n., L. rugosum sp. n., and L. chinense sp. n., are described following observations of live cells and protargol‐impregnated specimens. All three species usually have two macronuclear nodules and prominent warts along the dorsal margin formed by clustered extrusomes. In addition, L. caudatum sp. n. is characterized by its long conspicuous tail, dot‐like cortical granules, 4 or 5 left and 9 or 10 right kineties, and a single subterminal contractile vacuole. Loxophyllum rugosum sp. n. is distinguished by possessing three prominent ridges on the left side, 7–11 right and 5–7 left kineties. Loxophyllum chinense sp. n. is characterized by having several contractile vacuoles distributed along the ventral margin, 13–18 right and 6–8 left kineties. The small subunit ribosomal DNA (SSU rDNA) sequence similarities among six congeners range from 96.46% to 99.94%. Phylogenetic trees based on the SSU rDNA sequences indicate that all Loxophyllum spp. form a well‐supported monophyletic group. A brief review of the marine and brackish Loxophyllum species is supplied and one new combination, Litonotus multiplicatus (Kahl 1931) comb. n. (basionym Loxophyllum multiplicatum Kahl 1931), and one new name, Litonotus dragescoi nom. n. (basionym L. fasciolatus Dragesco 1966), are suggested.     

The mechanisms for nitration and nitrotyrosine formation in vitro and in vivo: Impact of diet

The detection of 3-nitro-L-tyrosine residues associated with many disease states, including gastric cancer, has implicated a role for peroxynitrite in vivo, and thus endogenously produced nitric oxide and superoxide. Additionally, dietary nitrate has been suggested to be involved in the pathogenesis of gastric cancer through a mechanism involving reduction to nitrite and subsequent formation of potentially mutagenic nitrosocompounds. Studies have now demonstrated that a multitude of reactive nitrogen species other than peroxynitrite are capable of producing nitrotyrosine. Thus, we have reviewed the evidence that dietary nitrate, amongst other reactive nitrogen species, may contribute to the body burden of nitrotyrosine.     

Mitochondrial Src tyrosine kinase plays a role in the cardioprotective effect of ischemic preconditioning by modulating complex I activity and mitochondrial ROS generation

Abstract

While ischemic preconditioning (IPC) and other cardioprotective interventions have been proposed to protect the heart from ischemia/reperfusion (I/R) injury by inhibiting mitochondrial complex I activity upon reperfusion, the exact mechanism underlying the modulation of complex I activity remains elusive. This study was aimed to test the hypothesis that IPC modulates complex I activity at reperfusion by activating mitochondrial Src tyrosine kinase, and induces cardioprotection against I/R injury. Isolated rat hearts were preconditioned by three cycles of 5-min ischemia and 5-min reperfusion prior to 30-min index ischemia followed by 2 h of reperfusion. Mitochondrial Src phosphorylation (Tyr⁴¹⁶) was dramatically decreased during I/R, implying inactivation of Src tyrosine kinase by I/R. IPC increased mitochondrial Src phosphorylation upon reperfusion and this was inhibited by the selective Src tyrosine kinase inhibitor PP2. IPC's anti-infarct effect was inhibited by the selective Src tyrosine kinase inhibitor PP2. Complex I activity was significantly increased upon reperfusion, an effect that was prevented by IPC in a Src tyrosine kinase-dependent manner. In support, Src and phospho-Src were found in complex I. Furthermore, IPC prevented hypoxia/reoxygenation-induced mitochondrial reactive oxygen species (ROS) generation and cellular injury in rat cardiomyocytes, which was revoked by PP2. Finally, IPC reduced LDH release induced by both hypoxia/reoxygenation and simulated ischemia/reperfusion, an effect that was reversed by PP2 and Src siRNA. These data suggest that mitochondrial Src tyrosine kinase accounts for the inhibitory action of IPC on complex I and mitochondrial ROS generation, and thereby plays a role in the cardioprotective effect of IPC.     

Imaging mitochondrial reactive oxygen species with fluorescent probes: Current applications and challenges

Abstract

Mitochondrial reactive oxygen species (ROS) is a key element in the regulation of several physiological functions and in the development or progression of multiple pathological events. A key task in the study of mitochondrial ROS is to establish reliable methods for measuring the ROS level in mitochondria with high selectivity, sensitivity, and spatiotemporal resolution. Over the last decade, imaging tools with fluorescent indicators from either small-molecule dyes or genetically encoded probes that can be targeted to mitochondria have been developed, which provide a powerful method to visualize and even quantify mitochondrial ROS level not only in live cells, but also in live animals. These innovative tools that have bestowed exciting new insights in mitochondrial ROS biology have been further promoted with the invention of new techniques in indicator design and fluorescent detection. However, these probes present some limitations in terms of specificity, sensitivity, and kinetics; failure to recognize these limitations often results in inappropriate interpretations of data. This review evaluates the recent advances in mitochondrial ROS imaging approaches with emphasis on their proper application and limitations, and highlights the future perspectives in the development of novel fluorescent probes for visualizing all species of ROS.     

N-acetylcysteine amide,a thiol antioxidant,prevents bleomycin-induced toxicity in human alveolar basal epithelial cells (A549)

Abstract

Bleomycin (BLM), a glycopeptide antibiotic from Streptomyces verticillus, is an effective antineoplastic drug. However, its clinical use is restricted due to the wide range of associated toxicities, especially pulmonary toxicity. Oxidative stress has been implicated as an important factor in the development of BLM-induced pulmonary toxicity. Previous studies have indicated disruption of thiol-redox status in lungs (lung epithelial cells) upon BLM treatment. Therefore, this study focused on (1) investigating the oxidative effects of BLM on lung epithelial cells (A549) and (2) elucidating whether a well-known thiol antioxidant, N-acetylcysteine amide (NACA), provides any protection against BLM-induced toxicity. Oxidative stress parameters, such as glutathione (GSH), malondialdehyde (MDA), and antioxidant enzyme activities were altered upon BLM treatment. Loss of mitochondrial membrane potential (ΔΨm), as assessed by fluorescence microscopy, indicated that cytotoxicity is possibly mediated through mitochondrial dysfunction. Pretreatment with NACA reversed the oxidative effects of BLM. NACA decreased the reactive oxygen species (ROS) and MDA levels and restored the intracellular GSH levels. Our data showed that BLM induced A549 cell death by a mechanism involving oxidative stress and mitochondrial dysfunction. NACA had a protective role against BLM-induced toxicity by inhibiting lipid peroxidation, scavenging ROS, and preserving intracellular GSH and ΔΨm. NACA can potentially be developed into a promising adjunctive therapeutic option for patients undergoing chemotherapy with BLM.     

Hepatocyte-specific distribution of catalase and its inhibitory effect on hepatic ischemia/reperfusion injury in mice

To explore the possibility of using catalase for the treatment of reactive oxygen species (ROS)-mediated injuries, the pharmacokinetics of bovine liver catalase (CAT) labeled with ¹¹¹In was investigated in mice. At a dose of 0.1 mg/kg, more than 70% of ¹¹¹In-CAT was recovered in the liver within 10 min after intravenous injection. In addition, ¹¹¹In-CAT was predominantly recovered from the parenchymal cells (PC) in the liver. Increasing the dose retarded the hepatic uptake of ¹¹¹In-CAT, suggesting saturation of the uptake process. This cell-specific uptake could not be inhibited by coadministration of various compounds which are known to be taken up by liver PC, indicating that the uptake mechanism of CAT by PC is very specific to this compound. The preventive effect of CAT on a hepatic ischemia/reperfusion injury was examined in mice by measuring the GOT and GPT levels in plasma. A bolus injection of CAT at 5 min prior to the reperfusion attenuated the increase in the levels of these indicators in a dose-dependent manner. These results suggest that catalase can be used for various hepatic injuries caused by ROS.