Hipk2 cooperates with p53 to suppress γ-ray radiation-induced mouse thymic lymphoma

A genome-wide screen for genetic alterations in radiation-induced thymic lymphomas generated from p53+/− and p53−/− mice showed frequent loss of heterozygosity (LOH) on chromosome 6. Fine mapping of these LOH regions revealed three non-overlapping regions, one of which was refined to a 0.2 Mb interval that contained only the gene encoding homeobox-interacting protein kinase 2 (Hipk2). More than 30% of radiation-induced tumors from both p53+/− and p53−/− mice showed heterozygous loss of one Hipk2 allele. Mice carrying a single inactive allele of Hipk2 in the germline were susceptible to induction of tumors by γ-radiation, but most tumors retained and expressed the wild-type allele, suggesting that Hipk2 is a haploinsufficient tumor suppressor gene for mouse lymphoma development. Heterozygous loss of both Hipk2 and p53 confers strong sensitization to radiation-induced lymphoma. We conclude that Hipk2 is a haploinsufficient lymphoma suppressor gene

Technical Design Report EuroGammaS proposal for the ELI-NP Gamma beam System

The machine described in this document is an advanced Source of up to 20 MeV Gamma Rays based on Compton back-scattering, i.e. collision of an intense high power laser beam and a high brightness electron beam with maximum kinetic energy of about 720 MeV. Fully equipped with collimation and characterization systems, in order to generate, form and fully measure the physical characteristics of the produced Gamma Ray beam. The quality, i.e. phase space density, of the two colliding beams will be such that the emitted Gamma ray beam is characterized by energy tunability, spectral density, bandwidth, polarization, divergence and brilliance compatible with the requested performances of the ELI-NP user facility, to be built in Romania as the Nuclear Physics oriented Pillar of the European Extreme Light Infrastructure. This document illustrates the Technical Design finally produced by the EuroGammaS Collaboration, after a thorough investigation of the machine expected performances within the constraints imposed by the ELI-NP tender for the Gamma Beam System (ELI-NP-GBS), in terms of available budget, deadlines for machine completion and performance achievement, compatibility with lay-out and characteristics of the planned civil engineering

Stretch-activated ion channel TMEM63B associates with developmental and epileptic encephalopathies and progressive neurodegeneration

By converting physical forces into electrical signals or triggering intracellular cascades, stretch-activated ion channels allow the cell to respond to osmotic and mechanical stress. Knowledge of the pathophysiological mechanisms underlying associations of stretch-activated ion channels with human disease is limited. Here, we describe 17 unrelated individuals with severe early-onset developmental and epileptic encephalopathy (DEE), intellectual disability, and severe motor and cortical visual impairment associated with progressive neurodegenerative brain changes carrying ten distinct heterozygous variants of TMEM63B, encoding for a highly conserved stretch-activated ion channel. The variants occurred de novo in 16/17 individuals for whom parental DNA was available and either missense, including the recurrent p.Val44Met in 7/17 individuals, or in-frame, all affecting conserved residues located in transmembrane regions of the protein. In 12 individuals, hematological abnormalities co-occurred, such as macrocytosis and hemolysis, requiring blood transfusions in some. We modeled six variants (p.Val44Met, p.Arg433His, p.Thr481Asn, p.Gly580Ser, p.Arg660Thr, and p.Phe697Leu), each affecting a distinct transmembrane domain of the channel, in transfected Neuro2a cells and demonstrated inward leak cation currents across the mutated channel even in isotonic conditions, while the response to hypo-osmotic challenge was impaired, as were the Ca2+ transients generated under hypo-osmotic stimulation. Ectopic expression of the p.Val44Met and p.Gly580Cys variants in Drosophila resulted in early death. TMEM63B-associated DEE represents a recognizable clinicopathological entity in which altered cation conductivity results in a severe neurological phenotype with progressive brain damage and early-onset epilepsy associated with hematological abnormalities in most individuals. Genetics of disease, diagnosis and treatmen

Petrological characterization of mantle xenoliths from Handler Ridge, Northern Victoria Land (Antarctica)

A study of ultramafic xenoliths in Cenozoic alkali basalts from Handler Ridge has been carried out in order to characterize the petrological features of the lithospheric mantle beneath Handler Ridge, Northern Victoria Land (NVL) and to extend the petrological knowledge of the mantle over a large portion of the Western Antarctic Rift, from M.te Melbourne (7421’S 16442’E) to Handler Ridge (7231’S 16718’E). Xenoliths are anhydrous spinel(sp) bearing lherzolites. Two textural types were recognized: i) medium to coarse grain protogranular and ii) fine grain equigranular. Some xenoliths present evidences of peridotite-melt interactions, such as spongy textures, cloudy rims and glassy patches. Large primary sp are often lobated. Newly formed, secondary crystals are referred to cpx only. Regardless textural types, olivine (ol) is forsteritic in composition with Fo varying from 87.5 to 91.0, with a more fertile group ranging between 87.6 and 88.6. NiO contents between 0.31 and 0.44 wt% match the typical mantle values. As observed in ol, orthopyroxene (opx) can be distinguished in two clusters: the more fertile group with mg# [=Mg/(Mg+Fe)*100 mol] ranging between 87.6 and 88.3 and the more residual one with mg# from 88.9 to 91.0. In cpx mg# varies between 87.06 and 91.7. Cpx in depleted lherzolite and secondary cpx are characterized by high values of Na2O (1.3-1.63 wt%) and Al2O3 (4.62-6.62 wt%). Glasses are SiO2 (55.50 wt%) oversaturated with TiO2 content between 0.6 and 1wt% and Na2O/K2O in the range of 0.80-2.02. Sp are characterized by mg# values between 62 and 78, and cr# [=Cr/(Cr+Al)*100 mol] from 14 to 42 with the usual negative correlation between the two parameters. The relationship between ol, opx and sp suggest that partial melting is the main process controlling the chemical variation of these three phases, while cpx were affected by metasomatic event/s. On the basis of the formalism of Brey & Kohler (1990), Liermann & Ganguly (2003) and Ballhaus (1991) Mg/Fe partitiong between unmetasomatized ol, opx and sp in all samples reflect equilibrium conditions, which can allow to calculate T and fO2 parameters. Assuming a P of 20 kbar, calculated T ranges from 1061 to 1140C, while DlogFQM reflects relatively high oxidation condition (-0.59 +0.30) of the unmetasomatized peridotite ambient. These preliminary results compared with data from other localities in NVL (Baker Rocks and Greene Point Coltorti et al., 2004) suggest that the anhydrous mantle domains related to the Antarctic Rift System is more oxidized with respect to amphibole-bearing mantle domains,in agreement with what recently proposed by Bonadiman et al.(2014). References Ballhaus (1991) CMP 106, 27-40 Brey & Kohler (1990) J. Petrol. 31, 1353-1378 Bonadiman et al., (2014) CMP, in press Coltorti et. al., (2004) Lithos 75, 115-139 Liermann & Ganguly (2003) CMP 145, 217-22

Petrological features of anhydrous and hydrous mantle xenoliths from Harrow Peaks, Antarctica

A preliminary study on the petrological features of a new xenoliths population, collected in the area of Harrow Peaks (HP) Northern Victoria Land, Antarctica is presented. The presence of modal hydrous phases (amphibole and rare phlogopite) allows to explore the water circulation and volatile reservoirs of this mantle domain. HP samples are medium to coarse grain peridotites, protogranular to phorphyroclastic in texture. They vary in composition from fertile lherzolite to harzburgite. Both anhydrous and hydrous peridotites show matrix/melt interaction forming secondary minerals and resorbed rims in primary olivines and spongy textures or cloudy rims of the other peridotite minerals. Opx occur as large crystals (opx1) with thin and resorbed spongy rims or texturally well equilibrated small, elongated grains (opx2). Primary unmetasomatized cpx are rare, the majority is spongy, resorbed grains or newly formed small crystals. Spinel (sp) always occur as small anhedral crystals, or larger, often dendritic primary grains. Amphibole occurs both as disseminated and in veins; the latter frequently associated with newly formed, secondary cpx crystals (Coltorti et al.,2004). Glassy patches are rare, not associated with amphibole, but occur related to resorbed/spongy cpx and spinel(sp).Mineral and glass major element analyses evidence that HP peridotites are following a residual trend, but are characterized by low mg#[=100*Mg/Mg+Fetot]values. Fo in primary unmetasomatized olivine range between 87.49 and 89.07 reflecting an anomalous fertile character respect to the lithological type (PM ol: Fo= 89.5). CaO(< 0.1 wt%)and NiO(0.28 to 0.41 wt%) contents are in the range of variably residual mantle values. In term of mg# values (87.24 - 89.56),opx1 and opx2 are coherent with primary ol. Both types show a narrow range of variation in terms of Al2O3(2.11-3.32 wt%), TiO2(0.05-0.14 wt%) and CaO(0.36-0.96 wt%). Spongy rims and resorbed crystals in both olivine and opx record a sensible enrichment in iron contents, accompanied (opx1 rim) by relevant depletion in Al2O3 and CaO. Primary and unmetasomatized portions of spongy cpx preserve primary residual chemical features in terms of mg#(89.19-90.87) and Al2O3(3.50-4.50 wt%), whereas TiO2 is anomalously high (0.47-0.6 wt%). In spongy and secondary cpx, effects of metasomatism at depth is evidenced by relatively higher mg# and low to very low TiO2 and Al2O3 contents, while the interaction with the host basalts univocally is testified by a coherent trend of the same elements. Sp follow the expected negative correlation between cr# [= Cr/(Cr+Al)*100 mol] and mg#, beside the strong textural evidence of matrix/melt interaction. Amphibole are pargasites (mg# 87.2-89.5) relatively homogeneous in composition with TiO2 ranging from 1.65 to 2.53 wt%. The few data so far available indicate T in the range 940 -1194 C and relatively low condition of log FMQ (-1.11; -0.25),comparable to the nearby hydrous xenolith locality of Baker Rocks. As already suggested by Bonadiman et al.(2014)the presence of amphibole do not necessarily mean high oxidation conditions. References: Bonadiman et al., (2014) CMP, in press Coltorti et. al., (2004) Lithos 75, 115-13

Petrological study of Cenozoic basic lavas and melt inclusions from Northern Victoria Land (Antartica)

This study offers a first view of the petrologic features of basic lavas and melt inclusions (MI) in olivine phenocrysts from Northern Victoria Land (Antartica). Samples were collected during three Italian expeditions with the aim of comparing major element composition and volatile content in the lavas and their mantle sources. Major elements and volatiles (H2O, CO2, S, F and Cl) were analyzed in MI, while major and trace elements were carried out on lavas from three localities, Eldridge Bluff, Shield Nunatak and Handler Ridge. Lavas are olivine-phyric (up to 15 %vol) with minor clinopyroxene and plagioclase in a glassy to microcristalline plagioclase-dominated groundmass; opaque minerals are mostly magnetites and subordinately ilmenites. The great majority of lavas are basanites (42.20-45.02 wt% SiO2 ,with 3.36-4.21 wt% of Na2O+K2O) with Mg# (MgO/(MgO+FeO) mol%, Fe2O3=0.15FeO) ranging from 44.87 to 60.83. Lavas from Handler Ridge are the most primitive. At similar fractionation degree, however two series can be distinguished based on K2O and trace element contents (Rb, Ba, La, Nb and Zr). MI in olivine phenocrysts from Shield Nunatak basanites were analysed. They are comparable to the host lavas but encompasse a wider range in composition (43.68 to 48.73 wt% SiO2, with 2.81-4.55 wt% of Na2O+K2O) and Mg# 49.51 to 74.44). The great majority of olivine in equilibrium with MI are more forsteritic than the enclosing crystal suggesting that MI were trapped from a less evolved magma or, most probaby, that Mg-Fe interdiffusion occurred between olivine and MI after entrapment. Most of MI have H2O content ranging from 0.70 wt% to 1.19 wt% and CO2 from 25 ppm to 341 ppm (H2O/CO2~1). At comparable H2O contents few samples show a remarkable higher CO2 values (1322 ppm to 3905 ppm) with a H2O/CO2 down to 0.8

Nature and evolution of the northern Victoria Land lithospheric mantle (Antarctica) as revealed by ultramafic xenoliths

A review of northern Victoria Land ultramafic xenoliths, collected and studied over more than 30 years, was carried out. More than 200 samples were gathered and characterized in a coherent and comparative manner, both for mantle-derived and cumulate xenoliths. Almost 2000 analyses of major elements and more than 300 analyses of trace elements of in situ and separated olivine, pyroxenes, amphibole, spinel and glass were taken into consideration. Particular attention was devoted to mantle lithologies in order to emphasize the composition and the evolution of this portion of the subcontinental lithosphere. The three main localities in northern Victoria Land where mantle xenoliths were found (i.e. Mount Melbourne (Baker Rocks), Greene Point and Handler Ridge), over a &gt;200 km distance, were described and compared with ultramafic xenoliths in three other localities (Harrow Peaks, Browning Pass and Mount Overlord) that are mainly cumulate in nature. Altogether, these data enabled us to reconstruct a long evolutionary history, from old depletion to most recent refertilization and metasomatic events, for this large sector of the northern Victoria Land subcontinental lithospheric mantle

Phlogopite-pargasite coexistence in an oxygen reduced spinel-peridotite ambient

The occurrence of phlogopite and amphibole in mantle ultramafic rocks is widely accepted as the modal effect of metasomatism in the upper mantle. However, their simultaneous formation during metasomatic events and the related sub-solidus equilibrium with the peridotite has not been extensively studied. In this work, we discuss the geochemical conditions at which the pargasite-phlogopite assemblage becomes stable, through the investigation of two mantle xenoliths from Mount Leura (Victoria State, Australia) that bear phlogopite and the phlogopite + amphibole (pargasite) pair disseminated in a harzburgite matrix. Combining a mineralogical study and thermodynamic modelling, we predict that the P\u2013T locus of the equilibrium reaction pargasite + forsterite = Na-phlogopite + 2 diopside + spinel, over the range 1.3\u20133.0 GPa/540\u20131500\ua0K, yields a negative Clapeyron slope of -0.003 GPa K\u20131 (on average). The intersection of the P\u2013T locus of supposed equilibrium with the new mantle geotherm calculated in this work allowed us to state that the Mount Leura xenoliths achieved equilibrium at 2.3 GPa /1190\ua0K, that represents a plausible depth of ~ 70\ua0km. Metasomatic K-Na-OH rich fluids stabilize hydrous phases. This has been modelled by the following equilibrium equation: 2 (K,Na)-phlogopite + forsterite = 7/2 enstatite + spinel + fluid (components: Na2O,K2O,H2O). Using quantum-mechanics, semi-empirical potentials, lattice dynamics and observed thermo-elastic data, we concluded that K-Na-OH rich fluids are not effective metasomatic agents to convey alkali species across the upper mantle, as the fluids are highly reactive with the ultramafic system and favour the rapid formation of phlogopite and amphibole. In addition, oxygen fugacity estimates of the Mount Leura mantle xenoliths [\u394(FMQ) = \u20131.97 \ub1 0.35; \u20131.83 \ub1 0.36] indicate a more reducing mantle environment than what is expected from the occurrence of phlogopite and amphibole in spinel-bearing peridotites. This is accounted for by our model of full molecular dissociation of the fluid and incorporation of the O-H-K-Na species into (OH)-K-Na-bearing mineral phases (phlogopite and amphibole), that leads to a peridotite metasomatized ambient characterized by reduced oxygen fugacity