ALBERT

Beschreibung: Pin1 modulates p63α protein stability in regulation of cell survival, proliferation and tumor formation Cell Death and Disease 4, e943 (December 2013). doi:10.1038/cddis.2013.468 Authors: C Li, D L Chang, Z Yang, J Qi, R Liu, H He, D Li & Z X Xiao

Beschreibung: Piperlongumine induces autophagy by targeting p38 signaling Cell Death and Disease 4, e824 (October 2013). doi:10.1038/cddis.2013.358 Authors: Y Wang, J-W Wang, X Xiao, Y Shan, B Xue, G Jiang, Q He, J Chen, H-G Xu, R-X Zhao, K D Werle, R Cui, J Liang, Y-L Li & Z-X Xu

Beschreibung: Basaltic lavas from Hainan Island near the northern edge of the South China Sea have an age range of between late Miocene (about 13 Ma) and Holocene, with a peak age of late Pliocene to middle Pleistocene. The basaltic province is dominated by tholeiites with subordinate alkali basalts. Most analysed samples display light rare earth element (LREE) enriched REE patterns and ocean island basalt (OIB)-like incompatible element distributions. The basalts contain abundant undeformed high-Mg olivine phenocrysts (up to Fo 90·7 ) that are high in CaO and MnO, indicating high-magnesian parental magmas. Independent barometers indicate that clinopyroxenes in the basalts crystallized over a wide range of pressures of 2–25 kbar (dominantly at 10–15 kbar) and that the melt cooled from about 1350°C to 1100°C during their crystallization. The compositional characteristics of the basalts indicate that their generation most probably involved both low-silica and high-silica melts, as represented by the alkali basalts and tholeiites, respectively. Our results show that the source region for the Hainan basalts is highly heterogeneous. The source for the tholeiites is mainly composed of peridotite and recycled oceanic crust, whereas the source for the bulk of the low-Th alkali basalts consists predominantly of peridotite and low-silica eclogite (garnet pyroxenite). Some high-Th (≥ 4 ppm) alkali basalts may have been produced by partial melting of low-silica garnet pyroxenite (eclogite). We estimated the primary melt compositions for the Hainan basalts using the most forsteritic olivine (Fo 90·7 ) composition and the most primitive bulk-rock samples (MgO 〉 9·0 wt % and CaO 〉8·0 wt %), assuming a constant Fe–Mg exchange partition coefficient of K D = 0·31 and Fe 3+ /Fe T = 0·1. The effective melting pressure ( P f ) and melting temperature ( T ) of the primary melts are P f = 18–32 kbar (weighted average = 23·8 ± 1·8 kbar) and T = 1420–1520°C for the tholeiites, and P f = 25–32 (weighted average = 28·3 ± 1·4 kbar) and T = 1480–1530°C for the alkali basalts. The P f – T data form an array that plots systematically above the dry lherzolite solidus but below the base of the lithosphere (~55 km) and intersects the dry peridotite solidus at a pressure of about 50 kbar. The mantle potential temperature beneath Hainan Island, based on the estimate primary melt compositions, varies from about 1500 to 1580°C with a weighted average of 1541 ± 10°C. The high-magnesian olivine phenocrysts, high mantle potential temperature, and the presence of recycled oceanic crust in the source region provide independent support for the Hainan plume model that has previously been proposed largely based on geophysical observations. The Hainan plume thus provides a rare example of a young mantle plume associated with deep slab subduction.

Beschreibung: Liver kinase B1 regulates the centrosome via PLK1 Cell Death and Disease 5, e1157 (April 2014). doi:10.1038/cddis.2014.135 Authors: K Werle, J Chen, H-G Xu, R-X Zhao, Q He, C Lu, R Cui, J Liang, Y-L Li & Z-X Xu

Beschreibung: Previous analysis of systems pharmacology has revealed a tendency of rational drug design in the pharmaceutical industry. The targets of new drugs tend to be close with the corresponding disease genes in the biological networks. However, it remains unclear whether the rational drug design introduces disadvantages, i.e. side effects. Therefore, it is important to dissect the relationship between rational drug design and drug side effects. Based on a recently released drug side effect database, SIDER, here we analyzed the relationship between drug side effects and the rational drug design. We revealed that the incidence drug side effect is significantly associated with the network distance of drug targets and diseases genes. Drugs with the distances of three or four have the smallest incidence of side effects, whereas drugs with the distances of more than four or smaller than three show significantly greater incidence of side effects. Furthermore, protein drugs and small molecule drugs show significant differences. Drugs hitting membrane targets and drugs hitting cytoplasm targets also show differences. Failure drugs because of severe side effects show smaller network distances than approved drugs. These results suggest that researchers should be prudent on rationalizing the drug design. Too small distances between drug targets and diseases genes may not always be advantageous for rational design for drug discovery.

Beschreibung: Coeval potassic adakite-like and shoshonitic felsic intrusions in the western Yunnan province of SW China are spatially and temporally associated with Eocene–Oligocene shoshonitic mafic volcanic rocks. The shoshonitic syenite and quartz monzonite intrusions are characterized by high K 2 O contents (4·9–6·8 wt %) and K 2 O/Na 2 O ratios (1·1–1·7), high Y (1·7–34·8 ppm) and Yb (1·50–3·16 ppm) contents, nearly flat heavy rare earth element (HREE) patterns and moderate Eu anomalies (Eu/Eu* = 0·65–0·78). The potassic adakite-like granite and quartz monzonite intrusions are characterized by enrichment in light rare earth elements (LREE), depletion in HREE and fractionated HREE patterns, high Sr (328–1423 ppm), Sr/Y (38–243) and La/Yb (23–62), and low Y and Yb contents. The shoshonitic syenite and quartz monzonites have the same Sr–Nd–Pb isotope compositions as the shoshonitic mafic volcanic rocks. They define linear trends on Harker diagrams, and have similar REE and trace element patterns to the shoshonitic mafic volcanic rocks. These observations suggest that the shoshonitic syenite and quartz monzonite magmas were differentiated from parental shoshonitic mafic melts by fractional crystallization of olivine, clinopyroxene and feldspar. The parent magmas originated from a metasomatized lithospheric mantle source. The shoshonitic syenite and quartz monzonites have higher magmatic zircon 18 O values (6·26–7·05) than the mantle, which suggests some 18 O enrichment during earlier subduction-related metasomatism of their lithospheric mantle source. The potassic adakite-like granites have Sr–Nd–Pb isotopic compositions that overlap those of lower-crustal amphibolites. They have low Mg#, MgO, Ni and Cr contents, abundant inherited zircons, high zircon Hf (0–5·5) and mantle-like 18 O (4·78–6·25) values. These granites were plausibly derived by partial melting of a thickened, potassic, mafic, lower crust with minor input from an older igneous felsic component. The potassic adakite-like quartz monzonites contain abundant mafic microgranular enclaves, and have transitional major and trace element characteristics between the adakite-like granite and the shoshonitic mafic magma. The quartz monzonites generally have higher Mg#, MgO, Ni and Cr contents than the lower crust-derived adakite-like rocks. They have no inherited zircons and have uniform zircon Hf and 18 O values. It is suggested that they were derived by variable degrees of mixing between lower-crustal melts and shoshonitic mafic magmas. The coeval shoshonitic and potassic adakite-like rocks appear to be associated with thinning of overthickened lithospheric mantle along the trans-lithospheric Jinsha suture following the collision between India and Asia. This lithospheric thinning could have resulted in the upwelling of the asthenosphere beneath western Yunnan, which induced partial melting of the residual metasomatized lithospheric mantle as well as the thickened lower crust in the Eocene.

Beschreibung: One of the major geophysical discoveries concerning the Tibetan Plateau is the existence of unusually weak layers in the mid- to lower crust, a characteristic widely interpreted as the result of crustal melting. This interpretation, however, remains highly contentious, particularly when applied to northern Tibet where crustally derived magmatic rocks are scarce. Here we report the finding of tourmaline-bearing mica and biotite rhyolites in the Bukadaban–Malanshan area, southern Kunlun Range, near the northern margin of the Tibetan Plateau. Zircon U–Pb and whole-rock or mineral 40 Ar– 39 Ar analyses suggest that these rocks erupted between 9·0 and 1·5 Ma. These rocks are geochemically similar to Himalayan leucogranites (interpreted as crustal melts), with strongly peraluminous compositions, high SiO 2 contents (69·0–76·0 wt %), and clear negative Eu, Ba and Sr anomalies. They have low Nd (–5·8 to –8·6) and high 87 Sr/ 86 Sr (0·7125–0·7178), 206 Pb/ 204 Pb (18·59–18·70), 207 Pb/ 204 Pb (15·49–15·63) and 208 Pb/ 204 Pb (38·31–38·74) isotopic compositions as well as magmatic zircon Hf (–0·7 to –5·0) compositions similar to those of global marine sediments and Proterozoic–Triassic sedimentary rocks in northern Tibet. We suggest that the Bukadaban–Malanshan rhyolites were generated by dehydration melting of metasedimentary rocks at 0·5–1·2 GPa and 740–863°C. Our data not only confirm the occurrence of a partially molten zone in the mid- to lower crust beneath northern Tibet but also constrain the crustal melting to have existed from middle Miocene to Quaternary times. Adopting the crustal flow model, we further argue the importance of outward flowing of the melt-weakened crust in the formation of crustal inflation, surface uplift, and earthquakes along the northern margin of the Tibetan Plateau.