East Antarctic rifting triggers uplift of the Gamburtsev Mountains

The Gamburtsev Subglacial Mountains are the least understood tectonic feature on Earth, because they are completely hidden beneath the East Antarctic Ice Sheet. Their high elevation and youthful Alpine topography, combined with their location on the East Antarctic craton, creates a paradox that has puzzled researchers since the mountains were discovered in 1958. The preservation of Alpine topography in the Gamburtsevs may reflect extremely low long-term erosion rates beneath the ice sheet, but the mountains' origin remains problematic. Here we present the first comprehensive view of the crustal architecture and uplift mechanisms for the Gamburtsevs, derived from radar, gravity and magnetic data. The geophysical data define a 2,500-km-long rift system in East Antarctica surrounding the Gamburtsevs, and a thick crustal root beneath the range. We propose that the root formed during the Proterozoic assembly of interior East Antarctica (possibly about 1 Gyr ago), was preserved as in some old orogens and was rejuvenated during much later Permian (roughly 250 Myr ago) and Cretaceous (roughly 100 Myr ago) rifting. Much like East Africa, the interior of East Antarctica is a mosaic of Precambrian provinces affected by rifting processes. Our models show that the combination of rift-flank uplift, root buoyancy and the isostatic response to fluvial and glacial erosion explains the high elevation and relief of the Gamburtsevs. The evolution of the Gamburtsevs demonstrates that rifting and preserved orogenic roots can produce broad regions of high topography in continental interiors without significantly modifying the underlying Precambrian lithosphere.     

In vivo genome editing restores haemostasis in a mouse model of haemophilia

Editing of the human genome to correct disease-causing mutations is a promising approach for the treatment of genetic disorders. Genome editing improves on simple gene-replacement strategies by effecting in situ correction of a mutant gene, thus restoring normal gene function under the control of endogenous regulatory elements and reducing risks associated with random insertion into the genome. Gene-specific targeting has historically been limited to mouse embryonic stem cells. The development of zinc finger nucleases (ZFNs) has permitted efficient genome editing in transformed and primary cells that were previously thought to be intractable to such genetic manipulation. In vitro, ZFNs have been shown to promote efficient genome editing via homology-directed repair by inducing a site-specific double-strand break (DSB) at a target locus, but it is unclear whether ZFNs can induce DSBs and stimulate genome editing at a clinically meaningful level in vivo. Here we show that ZFNs are able to induce DSBs efficiently when delivered directly to mouse liver and that, when co-delivered with an appropriately designed gene-targeting vector, they can stimulate gene replacement through both homology-directed and homology-independent targeted gene insertion at the ZFN-specified locus. The level of gene targeting achieved was sufficient to correct the prolonged clotting times in a mouse model of haemophilia B, and remained persistent after induced liver regeneration. Thus, ZFN-driven gene correction can be achieved in vivo, raising the possibility of genome editing as a viable strategy for the treatment of genetic disease.     

Eukaryotic DNA damage checkpoint activation in response to double-strand breaks

Double-strand breaks (DSBs) are the most detrimental form of DNA damage. Failure to repair these cytotoxic lesions can result in genome rearrangements conducive to the development of many diseases, including cancer. The DNA damage response (DDR) ensures the rapid detection and repair of DSBs in order to maintain genome integrity. Central to the DDR are the DNA damage checkpoints. When activated by DNA damage, these sophisticated surveillance mechanisms induce transient cell cycle arrests, allowing sufficient time for DNA repair. Since the term “checkpoint” was coined over 20 years ago, our understanding of the molecular mechanisms governing the DNA damage checkpoint has advanced significantly. These pathways are highly conserved from yeast to humans. Thus, significant findings in yeast may be extrapolated to vertebrates, greatly facilitating the molecular dissection of these complex regulatory networks. This review focuses on the cellular response to DSBs in Saccharomyces cerevisiae, providing a comprehensive overview of how these signalling pathways function to orchestrate the cellular response to DNA damage and preserve genome stability in eukaryotic cells.     

Scientific Objectivity and Postphenomenological Perception

Don Ihde’s paper “Stretching the in-between: Embodiment and beyond” appears to me as a stimulating, topical text with a number of important arguments about human embodiment as a dynamic and epistemically relevant dimension to scientific knowledge production. But, indirectly, the text also raises some basic questions about how to describe the (current) scope of technoscientific knowledge, and the potentials of postphenomenology to deal with this complicated, multi-stable issue.     

Seasonality in the reproductive phenology ofFicus: Its evolution and consequences

Summary Ficus can only reproduce if they are pollinated by mutualistic wasps that breed within the figs. Pollen-loaded wasps enter the figs when the female flowers are receptive. Several weeks later, their offspring load pollen within the fig and then emerge. As individual trees typically produce crops of synchronous figs at long intervals, the shortlived wasps have to move to another, receptive, tree. The wasp population can only survive, and hence the fig population reproduce, if there are trees fruiting all over the year. When only few trees are present within a population gaps in the flowering sequence may lead to the extinction of the local pollinator population. Two models are presented. One investigates the number of trees necessary in order to sustain a local pollinator population when the tree population has a seasonal pattern of fruiting. The second model investigates how such a seasonal pattern may evolve within a fig population as a result of individual selection on the trees. It is shown that pollinator populations are fragilized under seasonal conditions. Hence, the breeding system ofFicus limits their expansion into highly seasonal habitats. Seasonal habitats may also lead to seasonal adjustment of male versus female investments and to the evolution of dioecy.     

Lactic dehydrogenase isoenzymes in various cell types of mouse liver

Zusammenfassung Mit einer einfachen Methode wird demonstriert, dass Lebergewebe von Mäusen in 2 Fraktionen verschiedener Menge an Bindegewebe zu trennen ist. Die an Bindegewebe reiche Fraktion zeigt Enzymaktivität in LDH 1, 2, 3, 4 und 5. Nach Entfernung des Bindegewebes wird die Aktivität der LDH 1, 2, 3 und 4 Isoenzyme des restierenden Lebergewebes reduziert.     

Antennae and the role of olfaction and contact stimulation in mate recognition by males of the pollinating fig wasp Ceratosolen gravelyi (Hymenoptera: Agaonidae)

Finding a mate is a crucial step in sexual reproduction. The mutualism between figs and their pollinators is exploited by many figwasps that develop within their galls and attain sexual maturity simultaneously. Male pollinators carry the specific burden of detecting and opening mating holes in galls containing conspecific females before mating with them. The mating behaviourand antennal sensilla of male pollinators associated with Ficus semicordata was investigated to understand mate recognition. Male Ceratosolen gravelyi located female-containing galls from a distance, but only attempted to chew a mating hole after antennal contact with the gall surface was made. They showed similar responses to females and body extracts but failed to respond to washed female bodies. This behaviour indicates that unidentified chemicals present on the body surfaces of females are sufficient to elicit olfactory attraction and tactile confirmation. Multiporous plate sensilla are candidates for olfactory reception from a distance while basiconic sensilla may be involved in contact chemoreceptor. All of the sensilla are highly localised, on the distal part of the terminal flagellomere, suggesting a response to selection for strong directionality in the complex odour environment of the fig in which messages produced by hundreds of females may confuse precise mate localisation.     

UDP-glucose ceramide glucosyltransferase activates AKT,promoted proliferation,and doxorubicin resistance in breast cancer cells

The UDP-glucose ceramide glucosyltransferase (UGCG) is a key enzyme in the synthesis of glycosylated sphingolipids, since this enzyme generates the precursor for all complex glycosphingolipids (GSL), the GlcCer. The UGCG has been associated with several cancer-related processes such as maintaining cancer stem cell properties or multidrug resistance induction. The precise mechanisms underlying these processes are unknown. Here, we investigated the molecular mechanisms occurring after UGCG overexpression in breast cancer cells. We observed alterations of several cellular properties such as morphological changes, which enhanced proliferation and doxorubicin resistance in UGCG overexpressing MCF-7 cells. These cellular effects seem to be mediated by an altered composition of glycosphingolipid-enriched microdomains (GEMs), especially an accumulation of globotriaosylceramide (Gb3) and glucosylceramide (GlcCer), which leads to an activation of Akt and ERK1/2. The induction of the Akt and ERK1/2 signaling pathway results in an increased gene expression of multidrug resistance protein 1 (MDR1) and anti-apoptotic genes and a decrease of pro-apoptotic gene expression. Inhibition of the protein kinase C (PKC) and phosphoinositide 3 kinase (PI3K) reduced MDR1 gene expression. This study discloses how changes in UGCG expression impact several cellular signaling pathways in breast cancer cells resulting in enhanced proliferation and multidrug resistance.