Choline-releasing glycerophosphodiesterase EDI3 links the tumor metabolome to signaling network activities

Recently, EDI3 was identified as a key factor for choline metabolism that controls tumor cell migration and is associated with metastasis in endometrial carcinomas. EDI3 cleaves glycerophosphocholine (GPC) to form choline and glycerol-3-phosphate (G3P). Choline is then further metabolized to phosphatidylcholine (PtdC), the major lipid in membranes and a key player in membrane-mediated cell signaling. The second product, G3P, is a precursor molecule for several lipids with central roles in signaling, for example lysophosphatidic acid (LPA), phosphatidic acid (PA) and diacylglycerol (DAG). LPA activates intracellular signaling pathways by binding to specific LPA receptors, including membrane-bound G protein-coupled receptors and the intracellular nuclear receptor, PPARγ. Conversely, PA and DAG mediate signaling by acting as lipid anchors that bind and activate several signaling proteins. For example, binding of GTPases and PKC to PA and DAG, respectively, increases the activation of signaling networks, mediating processes such as migration, adhesion, proliferation or anti-apoptosis—all relevant for tumor development. We present a concept by which EDI3 either directly generates signaling molecules or provides “membrane anchors” for downstream signaling factors. As a result, EDI3 links choline metabolism to signaling activities resulting in a more malignant phenotype.     

The ubiquity of iron

The importance of iron in living systems can be traced to the many complexes within which it is found, to its chemical mobility in undergoing oxidation-reduction reactions, and to the abundance of iron in Earth's crust. Iron is the most abundant element, by mass, in the Earth, constituting about 80% of the inner and outer cores of Earth. The molten outer core is about 8000 km in diameter, and the solid inner core is about 2400 km in diameter. Iron is the fourth most abundant element in Earth's crust. It is the chemically functional component of mononuclear iron complexes, dinuclear iron complexes, [2Fe-2S] and [4Fe-4S] clusters, [Fe-Ni-S] clusters, iron protophorphyrin IX, and many other complexes in protein biochemistry. Metals such as nickel, cobalt, copper, and manganese are present in the crust and could in principle function chemically in place of iron, but they are scarce in Earth's crust. Iron is plentiful because of its nuclear stability in stellar nuclear fusion reactions. It seems likely that other solid planets, formed by the same processes as Earth, would also foster the evolution of life and that iron would be similarly important to life on those planets as it is on Earth.     

Smyd3 regulates cancer cell phenotypes and catalyzes histone H4 lysine 5 methylation

Smyd3 is a lysine methyltransferase implicated in chromatin and cancer regulation. Here we show that Smyd3 catalyzes histone H4 methylation at lysine 5 (H4K5me). This novel histone methylation mark is detected in diverse cell types and its formation is attenuated by depletion of Smyd3 protein. Further, Smyd3-driven cancer cell phenotypes require its enzymatic activity. Thus, Smyd3, via H4K5 methylation, provides a potential new link between chromatin dynamics and neoplastic disease.     

Bioavailability of chromium(III)-supplements in rats and humans

Chromium(III) is long regarded as essential trace element but the biochemical function and even basic transport ways in the body are still unclear. For a more rational discussion on beneficial as well as toxic effects of Cr(III), we re-investigated the bioavailability of the most important oral Cr supplements by using radiolabeled compounds and whole-body-counting in rats and in the first time also in humans. The apparent absorption of (51)Cr(III) from Cr-picolinate, Cr-nicotinate, Cr-phenylalaninate, Cr-proprionate, or Cr-chloride was generally low (0.04-0.24?%) in rats with slightly higher values for Cr-chloride and -phenylalaninate. Taking a fast urine excretion into account, the true absorption of (51)Cr was clearly higher for CrPic(3) (0.99?%), probably indicating a different uptake mechanism of this rather stable organic Cr complex. The bioavailability of CrPic(3) and Cr(D: -Phen)(3), the leading compounds in actual investigations, was analysed also in human volunteer by intraindividual comparison. The apparent absorption (=Cr bioavailability) of (51)Cr from both compounds was substantially higher in humans (0.8-1?%) than in rats. Again, most of freshly absorbed CrPic(3) was excreted into the urine resulting in the same low whole-body retention after 7?days for both compounds. In summary, the bioavailability of Cr from pharmaceutical Cr compound is lower than hitherto assumed. Importantly, humans absorb Cr(III) clearly better than rats. The absorption mechanism of CrPic(3) seems to be different from ionic Cr(III) but, as only the same low amount of Cr is retained from this compound, it is also not more bioavailable than other Cr compounds.     

β-Barrel Mobility Underlies Closure of the Voltage-Dependent Anion Channel

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Highlights? The rigid N-terminal helix of VDAC stabilizes the cylindrical β-barrel ? Removal of the helix leads to elliptical, semicollapsed pore shapes ? Semicollapse can quantitatively explain conductance and selectivity of closed VDAC ? The N terminus acts as a switch controlling VDAC entry into the closed state     

Local adaptation and matching habitat choice in female barn owls with respect to melanic coloration

Local adaptation is a major mechanism underlying the maintenance of phenotypic variation in spatially heterogeneous environments. In the barn owl (Tyto alba), dark and pale reddish-pheomelanic individuals are adapted to conditions prevailing in northern and southern Europe, respectively. Using a long-term dataset from Central Europe, we report results consistent with the hypothesis that the different pheomelanic phenotypes are adapted to specific local conditions in females, but not in males. Compared to whitish females, reddish females bred in sites surrounded by more arable fields and less forests. Colour-dependent habitat choice was apparently beneficial. First, whitish females produced more fledglings when breeding in wooded areas, whereas reddish females when breeding in sites with more arable fields. Second, cross-fostering experiments showed that female nestlings grew wings more rapidly when both their foster and biological mothers were of similar colour. The latter result suggests that mothers should particularly produce daughters in environments that best match their own coloration. Accordingly, whiter females produced fewer daughters in territories with more arable fields. In conclusion, females displaying alternative melanic phenotypes bred in habitats providing them with the highest fitness benefits. Although small in magnitude, matching habitat selection and local adaptation may help maintain variation in pheomelanin coloration in the barn owl.     

Habitat stability affects dispersal and the ability to track climate change

Habitat persistence should influence dispersal ability, selecting for stronger dispersal in habitats of lower temporal stability. As standing (lentic) freshwater habitats are on average less persistent over time than running (lotic) habitats, lentic species should show higher dispersal abilities than lotic species. Assuming that climate is an important determinant of species distributions, we hypothesize that lentic species should have distributions that are closer to equilibrium with current climate, and should more rapidly track climatic changes. We tested these hypotheses using datasets from 1988 and 2006 containing all European dragon- and damselfly species. Bioclimatic envelope models showed that lentic species were closer to climatic equilibrium than lotic species. Furthermore, the models over-predicted lotic species ranges more strongly than lentic species ranges, indicating that lentic species track climatic changes more rapidly than lotic species. These results are consistent with the proposed hypothesis that habitat persistence affects the evolution of dispersal.     

miR-17-5p Regulates Endocytic Trafficking through Targeting TBC1D2/Armus

miRNA cluster miR-17-92 is known as oncomir-1 due to its potent oncogenic function. miR-17-92 is a polycistronic cluster that encodes 6 miRNAs, and can both facilitate and inhibit cell proliferation. Known targets of miRNAs encoded by this cluster are largely regulators of cell cycle progression and apoptosis. Here, we show that miRNAs encoded by this cluster and sharing the seed sequence of miR-17 exert their influence on one of the most essential cellular processes – endocytic trafficking. By mRNA expression analysis we identified that regulation of endocytic trafficking by miR-17 can potentially be achieved by targeting of a number of trafficking regulators. We have thoroughly validated TBC1D2/Armus, a GAP of Rab7 GTPase, as a novel target of miR-17. Our study reveals regulation of endocytic trafficking as a novel function of miR-17, which might act cooperatively with other functions of miR-17 and related miRNAs in health and disease.     

No Concordant Phylogeographies of the Rose Gall Wasp Diplolepis rosae (Hymenoptera,Cynipidae) and Two Associated Parasitoids across Europe

According to the Host-tracking Hypothesis, species of higher trophic levels with a close relationship to their hosts, such as parasites or parasitoids, are expected to show spatio-temporal phylogeographic patterns similar to those of their host. Alternatively, with ecological sorting, a subset of the local species pools might shift to a related host species, thereby disengaging common phylogeographic patterns. Here, we compare the phylogeographic structures of the cynipid rose gall wasp Diplolepis rosae across Europe and of two of its most common parasitoids, the wasps Orthopelma mediator and Glyphomerus stigma, by analysing the sequences of two gene fragments (COI and ITS 2). The phylogeographic structures of the three species associated with roses were incongruent. D. rosae had the lowest genetic diversity with one major clade, O. mediator showed the classical phylogeographic structure for Europe with one eastern and one western clade, and G. stigma had the highest diversity but no geographical structuring. This discordance of geographical patterns may be explained by 1) the dispersal propensity of adult parasitoids or 2) the parasitoids having the ability to switch to another host, while the primary host becomes rare or is even not available. Furthermore there was no indication that phylogenetic patterns were affected by Wolbachia infections. Our results document that communities of closely interacting species may be the result of idiosyncratic biogeographic histories.