Mechanism of cellular uptake of genotoxic silica nanoparticles.

Mechanisms for cellular uptake of nanoparticles have important implications for nanoparticulate drug delivery and toxicity. We have explored the mechanism of uptake of amorphous silica nanoparticles of 14 nm diameter, which agglomerate in culture medium to hydrodynamic diameters around 500 nm. In HT29, HaCat and A549 cells, cytotoxicity was observed at nanoparticle concentrations ≥ 1 μg/ml, but DNA damage was evident at 0.1 μg/ml and above. Transmission electron microscopy (TEM) combined with energy-dispersive X-ray spectroscopy confirmed entry of the silica particles into A549 cells exposed to 10 μg/ml of nanoparticles. The particles were observed in the cytoplasm but not within membrane bound vesicles or in the nucleus. TEM of cells exposed to nanoparticles at 4°C for 30 minutes showed particles enter cells when activity is low, suggesting a passive mode of entry. Plasma lipid membrane models identified physical interactions between the membrane and the silica NPs. Quartz crystal microbalance experiments on tethered bilayer lipid membrane systems show that the nanoparticles strongly bind to lipid membranes, forming an adherent monolayer on the membrane. Leakage assays on large unilamellar vesicles (400 nm diameter) indicate that binding of the silica NPs transiently disrupts the vesicles which rapidly self-seal. We suggest that an adhesive interaction between silica nanoparticles and lipid membranes could cause passive cellular uptake of the particles

Integrative analysis of DNA copy number, DNA methylation and gene expression in multiple myeloma reveals alterations related to relapse

Multiple myeloma (MM) remains incurable despite the introduction of novel agents, and a relapsing course is observed in most patients. Although the development of genomic technologies has greatly improved our understanding of MM pathogenesis, the mechanisms underlying relapse have been less thoroughly investigated. In this study, an integrative analysis of DNA copy number, DNA methylation and gene expression was conducted in matched diagnosis and relapse samples from MM patients. Overall, the acquisition of abnormalities at relapse was much more frequent than the loss of lesions present at diagnosis, and DNA losses were significantly more frequent in relapse than in diagnosis samples. Interestingly, copy number abnormalities involving more than 100 Mb of DNA at relapse significantly affect the gene expression of these samples, provoking a particular deregulation of the IL-8 pathway. On the other hand, no significant modifications of gene expression were observed in those samples with less than 100 Mb affected by chromosomal changes. Although several statistical approaches were used to identify genes whose abnormal expression at relapse was regulated by methylation, only two genes that were significantly deregulated in relapse samples (SORL1 and GLT1D1) showed a negative correlation between methylation and expression. Further analysis revealed that DNA methylation was involved in regulating SORL1 expression in MM. Finally, relevant changes in gene expression observed in relapse samples, such us downregulation of CD27 and P2RY8, were most likely not preceded by alterations in the corresponding DNA. Taken together, these results suggest that the genomic heterogeneity described at diagnosis remains at relapse.This work was partially supported by the Instituto de Salud Carlos III-Cofinanciación con fondos FEDER (PI080568, PS0901897 and PI13/00111), the Gerencia Regional de Salud, Junta de Castilla y León (GRS202/A08 and GRS 702/A/11), the Spanish Myeloma Network Program (RD06/0020/0006) and the Asociación Española Contra el Cáncer (AECC, GCB120981SAN).Peer Reviewe

CHARACTERIZING THE V -BAND LIGHT-CURVES OF HYDROGEN-RICH TYPE II SUPERNOVAE

We present an analysis of the diversity of V-band light-curves of hydrogen-rich type II supernovae. Analyzing a sample of 116 supernovae, several magnitude measurements are defined, together with decline rates at different epochs, and time durations of different phases. It is found that magnitudes measured at maximum light correlate more strongly with decline rates than those measured at other epochs: brighter supernovae at maximum generally have faster declining light-curves at all epochs. We find a relation between the decline rate during the 'plateau' phase and peak magnitudes, which has a dispersion of 0.56 magnitudes, offering the prospect of using type II supernovae as purely photometric distance indicators. Our analysis suggests that the type II population spans a continuum from low-luminosity events which have flat light-curves during the 'plateau' stage, through to the brightest events which decline much faster. A large range in optically thick phase durations is observed, implying a range in progenitor envelope masses at the epoch of explosion. During the radioactive tails, we find many supernovae with faster declining light-curves than expected from full trapping of radioactive emission, implying low mass ejecta. It is suggested that the main driver of light-curve diversity is the extent of hydrogen envelopes retained before explosion. Finally, a new classification scheme is introduced where hydrogen-rich events are typed as simply 'SNII' with an s2 value giving the decline rate during the 'plateau' phase, indicating its morphological type.Comment: Accepted for publication in ApJ. Revised edition corrects errors in affiliation number

Geochemical constraints on the origin of the mid-Palaeozoic diabases from the Holy Cross Mts. and Upper Silesia, southeastern Poland

A geochemical study of Palaeozoic diabase dykes and sills from the Holy Cross Mts. and Upper Silesian Block (southeastern Poland) has revealed that these diabases are most probably derived from fractional crystallization of three distinct primarymelts. All diabases are relatively evolved subalkaline tholeiites with low mg-numbers that vary between 50.7 and 60.5. Their mantle normalised incompatible element patterns are intermediate between that of enriched mid-ocean ridge basalt (E-MORB) and ocean island basalt (OIB). The compositional differences within the diabases are interpreted in terms of slightly variable degrees of partial melting of their mantle sources combined with variable degrees of subsequent gabbro fractionation in high-level magma chambers. Some incompatible element ratios (e.g. Zr/Nb, Y/Nb) in the diabases and Nd isotope data from the cogenetic diorites seem to be consistent with mixing of partial melts from both enriched lithospheric and depleted asthenospheric mantle sources. Both Upper Silesian and Holy Cross diabases show strong chemical similarity to the continental flood basalts (CFB), which are associated with extensional tectonics. The Bardo diabase, located in the northern part of the Małopolska Block, can be hypothetically linked to the detachment of this unit from the Baltica margin and subsequent displacement to its final position between the late Ludlovian and Emsian, whereas the Milejowice-Janowice diabase (Łysogóry Unit) possibly relates to the extension of the Baltica passive margin during the Late Silurian, in the final stage of its collision with East Avalonia

The Mława syenite alkaline intrusion – a perspective of rare earth elements occurrence

Obecność kilku alkalicznych i alkaliczno-ultramaficznych ciał w obrębie zakrytego podłoża kratonu wschodnioeuropejskiego na obszarze północno-wschodniej Polski była znana od dawna, na podstawie badań geofizycznych, jako wyraźne anomalie Ełku, Pisza, Tajna i Mławy. Jedynie cztery głębokie otwory wiertnicze na peryferiach anomalii Mławy (Płońsk IG 2A/2, Ciechanów 1, Konopki Wielkie 1 i Gradzanowo 2) odsłoniły syenity i kwarcowe syenity. Metaluminowe, bogate w pierwiastki ziem rzadkich (REE) i Zr syenity Mławy są względnie późnym produktem procesów frakcjonowania magmy. Analizy chemiczne w mikroobszarze potwierdziły obecność pierwotnych fluorowęglanów REE (bastnäsyt, parisyt) i obfitość cyrkonu jako faz bogatych w REE i Zr w syenitach. Istotna koncentracja minerałów nośników REE ma genetyczne i przestrzenne związki ze skałami alkalicznymi, dlatego intruzja Mławy powinna być obiektem dalszych badań.A number of alkaline and alkaline-ultramafic bodies have been known within the hidden basement of the East European Craton (EEC) in north-western Poland for a long time. These are the strong anomalies of Ełk, Pisz, Tajno and Mława identified based on a geophysical survey. Syenite and quartz syenites, were drilled by only four deep boreholes on the periphery of the Mława anomaly (Płońsk IG 2A/2, Ciechanów 1, Konopki Wielkie and Gradzanowo 2). The REE- and Zr-rich Mława metaluminous syenites are relatively late-stage products of fractionation processes. Electron microprobe analyses confirm primary-appearing REE-fluorocarbonate (bastnäsite–parisite) and zircon abundance as major host phases to REE and Zr in the syenites. A significant concentration of the REE-bearing minerals shows a genetic and spatial relation to an alkaline rocks, therefore the Mława igneous bodies should be the subject of further investigations

Geologic map of crystalline basement in the Polish part of the East European Platform : a summary of the study

A new geologic map of the crystalline basement of NE Poland has been constrained on the basis of the magnetic and gravity imaging, data from seismic profiles of POLONAISE'97 and CELEBRATION'2000, and extensive geochemical, isotopic and U-Pb dating studies of drill core samples. This updated reconstruction of the hidden southwestern margin of the East European Craton revealed of several late Svecofennian orogenic domains with ages in the range 2.0–1.74 Ga, belonging to the Fennoscandia. The age of these Paleoproterozoic domains is becoming regionally younger towards NW. Furthermore, there is two Paleoproterozoic domains, which form integral part of the westernmost youngest rim of the Sarmatia block. During the early Mesoproterozoic between 1.54 and 1.45 Ga intracratonic plutons of the AMCG suite intruded a large area of the Mazury-Warmia, Pomorze and SE Baltic region. Several deep-sourced ultramafic-alkaline bodies of Early Carboniferous age (354–338 Ma) are related to the youngest magmatic event

40Ar-39 Ar ages of selected rocks and minerals from the Kraków-Lubliniec Fault Zone, and their relation to the Paleozoic structural evolution of the Malopolska and Brunovistulian terranes (S Poland)

New 40Ar-39 Ar isotope ages of mafic and felsic rocks from the contact zone of the Malopolska and Brunovistulian terranes are presented and discussed. A 40Ar-39 Ar age estimation of detrital muscovite from a Lower Devonian "old red" type sandstone drilled on the Malopolska side of this zone was also done. Our studies reveal that three events of Paleozoic magmatic activity took place in the study area. The oldest, late Emsian episode is recorded by a diorite from the core part of an intrusion penetrated by the Sosnowiec IG 1 borehole. A younger, Visean event is documented by a diabase cored in the borehole WB-137. Diabases from Niedwiedzia Góra and from borehole PZ-10, and a rhyodacite from borehole 16-WB gave early Permian (Artinskian-early Sakmarian) ages. The youngest, middle Sakmarian age was obtained for a diabase forming the external parts of the Sosnowiec IG 1 polycyclic intrusion. A diorite penetrated by the Sosnowiec IG 1 borehole was emplaced during the late Emsian extension that preceded the Lochkovian-Pragian? transpression related to the final docking and amalgamation of the Brunovistulian Terrane

Collective Narcissism and Anti-Semitism in Poland: the Mediating Role of Siege Beliefs and the Conspiracy Stereotype of Jews

Two studies examined the relationship between collective narcissism - an emotional investment in an unrealistic belief about unparalleled greatness of an in-group (Golec de Zavala et al., 2009) - and anti-Semitism in Poland. The results indicate that this relationship is simultaneously mediated by (a) a belief that the in-group is constantly threatened by hostile intentions of other groups (Polish siege beliefs; Bar-Tal & Antebi, 1992) and (b) a belief that the Jewish out-group is particularly threatening because its members secretly aim to dominate the world (the conspiracy stereotype of Jews; Bergmann, 2008; Kofta & S?dek, 2005). The results confirm earlier findings that collective narcissism is linked to increased sensitivity to intergroup threat which drives its association with intergroup hostility. The sensitivity to intergroup threat is composed of beliefs about vulnerability of the in-group and hostility of the out-group