Phenotypic diversity of Thuridilla hopei (Verany, 1853) (Gastropoda Heterobranchia Sacoglossa). A DNA-barcoding approach

The sacoglossan Thuridilla hopei (Verany, 1853) shows highly diverse chromatic patterns. Based on the morphological examination of specimens from different Mediterranean localities, we have observed that in spite of this great variability in colours of T. hopei, two major chromatic morphotypes are related to bathymetry. Specimens from deeper water exhibit blue darker and more uniform patterns than individuals from shallower water, which show a more variable, dashed and spotted arrangement of light blue, yellow, orange, white and black pigmentation. A molecular genetic analysis using the mitochondrial COI and 16S rDNA markers has confirmed that all these extremely different chromatic morphotypes belong to a single specific entity, i.e. T. hopei, a sacoglossan with a wide distribution, from Macaronesia in the Atlantic, to the easternmost Mediterranean Sea

CD133 Is a Marker of Bioenergetic Stress in Human Glioma

Mitochondria dysfunction and hypoxic microenvironment are hallmarks of cancer cell biology. Recently, many studies have focused on isolation of brain cancer stem cells using CD133 expression. In this study, we investigated whether CD133 expression is regulated by bioenergetic stresses affecting mitochondrial functions in human glioma cells. First, we determined that hypoxia induced a reversible up-regulation of CD133 expression. Second, mitochondrial dysfunction through pharmacological inhibition of the Electron Transport Chain (ETC) produced an up-regulation of CD133 expression that was inversely correlated with changes in mitochondrial membrane potential. Third, generation of stable glioma cells depleted of mitochondrial DNA showed significant and stable increases in CD133 expression. These glioma cells, termed rho0 or ρ0, are characterized by an exaggerated, uncoupled glycolytic phenotype and by constitutive and stable up-regulation of CD133 through many cell passages. Moreover, these ρ0 cells display the ability to form “tumor spheroids” in serumless medium and are positive for CD133 and the neural progenitor cell marker, nestin. Under differentiating conditions, ρ0 cells expressed multi-lineage properties. Reversibility of CD133 expression was demonstrated by transfering parental mitochondria to ρ0 cells resulting in stable trans-mitochondrial “cybrid” clones. This study provides a novel mechanistic insight about the regulation of CD133 by environmental conditions (hypoxia) and mitochondrial dysfunction (genetic and chemical). Considering these new findings, the concept that CD133 is a marker of brain tumor stem cells may need to be revised

Salivary glands in predatory mollusks: Evolutionary considerations

Many marine mollusks attain or increase their predatory efficiency using complex chemical secretions, which are often produced and delivered through specialized anatomical structures of the foregut. The secretions produced in venom glands of Conus snails and allies have been extensively studied, revealing an amazing chemical diversity of small, highly constrained neuropeptides, whose characterization led to significant pharmacological developments. Conversely, salivary glands, the other main secretory structures of molluscan foregut, have been neglected despite their shared occurrence in the two lineages including predatory members: Gastropoda and Cephalopoda. Over the last few years, the interest for the chemistry of salivary mixtures increased based on their potential biomedical applications. Recent investigation with -omics technologies are complementing the classical biochemical descriptions, that date back to the 1950s, highlighting the high level of diversification of salivary secretions in predatory mollusks, and suggesting they can be regarded as a pharmaceutical cornucopia. As with other animal venoms, some of the salivary toxins are reported to target, for example, sodium and/or potassium ion channels or receptors and transporters for neurotransmitters such as, glutamate, serotonin, neurotensin, and noradrenaline, thus manipulating the neuromuscular system of the preys. Other bioactive components possess anticoagulant, anesthetic and hypotensive activities. Here, we overview available knowledge on the salivary glands of key predatory molluscan taxa, gastropods, and cephalopods, summarizing their anatomical, physiological and biochemical complexity in order to facilitate future comparative studies on main evolutionary trends and functional convergence in the acquisition of successful predatory strategies

Hidden biodiversity of Antarctic Marseniopsis (Velutinidae)

Marseniopsis Bergh, 1886 is a genus of marine gastropods (Velutinidae) which includes nine described species, eight of which endemic to Antarctica. This genus is known to feed on tunicates and is characterized by a peculiar planktotrophic larva, the “limacosphaera”, with a potentially long pelagic life, which is a really uncommon developmental strategy for Antarctic gastropods. In the framework of recent scientific expeditions held in the Ross Sea, at the tip of the Antarctic Peninsula and in Weddell sector, a special effort was done in documenting with digital pictures the colour pattern of the different species routinely encountered during sampling activities. Thanks to this live-collected new material, several different colour patterns, within and amongst presumed conspecific samples, were documented, suggesting the existence of at least a partially underestimated diversity. Based on this unprecedented large sampling, our aim was to define the actual diversity of the Antarctic Marseniopsis, including the identification of cryptic species through an integrative taxonomy approach. Our dataset included 78 COI barcode sequences, out of which 21 originate from 18 sampling sites in the Ross Sea and other 57 from 13 sampling sites in the Weddell Sea- Antarctic Peninsula. Through genetic distances, we identified 13 MOTUs, 9 of which exclusively from the Weddell Sea-Antarctic Peninsula and four occurring also in the Ross sea. Automatic Barcode Gap Discovery (ABGD) analysis confirmed the same samples partition and identified a barcoding gap around 2% of genetic distance. The isolation-by-distance analysis did not show any significant correlation between genetic and geographic distances among populations of each clade. These results suggest the presence of a hidden biodiversity of Antarctic Marseniopsis that, if confirmed by further analysis, will almost double the number of species of this genus. In addition, the absence of isolation-by-distance and the presence of some MOTUs in both seas, are congruent with the long pelagic life of the Marseniopsis larva

Phenotypic diversity of Thuridilla hopei (Vérany, 1853) (Gastropoda, Heterobranchia, Sacoglossa). A DNA-barcoding approach

Phenotypic diversity of Thuridilla hopei (Vérany, 1853) (Gastropoda, Heterobranchia, Sacoglossa). A DNA-barcoding approach

Expansion and neofunctionalization of actinoporin-like genes in Mediterranean mussel (Mytilus galloprovincialis).

Pore-forming toxins are an important component of the venom of many animals. Actinoporins are potent cytolysins that were first detected in the venom of sea anemones; however, they are occasionally found in animals other than cnidarians and are expanded in a few predatory gastropods. Here, we report the presence of 27 unique actinoporin-like genes with monophyletic origin in Mytilus galloprovincialis, which we have termed mytiporins. These mytiporins exhibited a remarkable level of molecular diversity and gene presence–absence variation, which warranted further studies aimed at elucidating their functional role. We structurally and functionally characterized mytiporin-1 and found significant differences from the archetypal actinoporin fragaceatoxin C. Mytiporin-1 showed weaker permeabilization activity, no specificity towards sphingomyelin, and weak activity in model lipid systems with negatively charged lipids. In contrast to fragaceatoxin C, which forms octameric pores, functional mytiporin-1 pores on negatively charged lipid membranes were hexameric. Similar hexameric pores were observed for coluporin-26 from Cumia reticulata and a conoporin from Conus andremenezi. This indicates that also other molluscan actinoporin-like proteins differ from fragaceatoxin C. Although the functional role of mytiporins in the context of molluscan physiology remains to be elucidated, the lineage-specific gene family expansion event that characterizes mytiporins indicates that strong selective forces acted on their molecular diversification. Given the tissue distribution of mytiporins, this process may have broadened the taxonomic breadth of their biological targets, which would have important implications for digestive processes or mucosal immunity

A novel Osmium-based compound targets the mitochondria and triggers ROS-dependent apoptosis in colon carcinoma

Engagement of the mitochondrial-death amplification pathway is an essential component in chemotherapeutic execution of cancer cells. Therefore, identification of mitochondria-targeting agents has become an attractive avenue for novel drug discovery. Here, we report the anticancer activity of a novel Osmium-based organometallic compound (hereafter named Os) on different colorectal carcinoma cell lines. HCT116 cell line was highly sensitive to Os and displayed characteristic features of autophagy and apoptosis; however, inhibition of autophagy did not rescue cell death unlike the pan-caspase inhibitor z-VADfmk. Furthermore, Os significantly altered mitochondrial morphology, disrupted electron transport flux, decreased mitochondrial transmembrane potential and ATP levels, and triggered a significant increase in reactive oxygen species (ROS) production. Interestingly, the sensitivity of cell lines to Os was linked to its ability to induce mitochondrial ROS production (HCT116 and RKO) as HT29 and SW620 cell lines that failed to show an increase in ROS were resistant to the death-inducing activity of Os. Finally, intra-peritoneal injections of Os significantly inhibited tumor formation in a murine model of HCT116 carcinogenesis, and pretreatment with Os significantly enhanced tumor cell sensitivity to cisplatin and doxorubicin. These data highlight the mitochondria-targeting activity of this novel compound with potent anticancer effect in vitro and in vivo, which could have potential implications for strategic therapeutic drug design. © 2013 Macmillan Publishers Limited All rights reserved