First order wetting of rough substrates and quantum unbinding

Replica and functional renormalization group methods show that, with short range substrate forces or in strong fluctuation regimes, wetting of a self-affine rough wall in 2D turns first-order as soon as the wall roughness exponent exceeds the anisotropy index of bulk interface fluctuations. Different thresholds apply with long range forces in mean field regimes. For bond-disordered bulk, fixed point stability suggests similar results, which ultimately rely on basic properties of quantum bound states with asymptotically power-law repulsive potentials.Comment: 11 pages, 1 figur

Evolution of dopant-induced helium nanoplasmas

Two-component nanoplasmas generated by strong-field ionization of doped helium nanodroplets are studied in a pump-probe experiment using few-cycle laser pulses in combination with molecular dynamics simulations. High yields of helium ions and a pronounced, droplet size-dependent resonance structure in the pump-probe transients reveal the evolution of the dopant-induced helium nanoplasma. The pump-probe dynamics is interpreted in terms of strong inner ionization by the pump pulse and resonant heating by the probe pulse which controls the final charge states detected via the frustration of electron-ion recombination

BCR and its mutants, the reciprocal t(9;22)-associated ABL/BCR fusion proteins, differentially regulate the cytoskeleton and cell motility

BACKGROUND: The reciprocal (9;22) translocation fuses the bcr (breakpoint cluster region) gene on chromosome 22 to the abl (Abelson-leukemia-virus) gene on chromosome 9. Depending on the breakpoint on chromosome 22 (the Philadelphia chromosome – Ph+) the derivative 9+ encodes either the p40((ABL/BCR) )fusion transcript, detectable in about 65% patients suffering from chronic myeloid leukemia, or the p96((ABL/BCR) )fusion transcript, detectable in 100% of Ph+ acute lymphatic leukemia patients. The ABL/BCRs are N-terminally truncated BCR mutants. The fact that BCR contains Rho-GEF and Rac-GAP functions strongly suggest an important role in cytoskeleton modeling by regulating the activity of Rho-like GTPases, such as Rho, Rac and cdc42. We, therefore, compared the function of the ABL/BCR proteins with that of wild-type BCR. METHODS: We investigated the effects of BCR and ABL/BCRs i.) on the activation status of Rho, Rac and cdc42 in GTPase-activation assays; ii.) on the actin cytoskeleton by direct immunofluorescence; and iii) on cell motility by studying migration into a three-dimensional stroma spheroid model, adhesion on an endothelial cell layer under shear stress in a flow chamber model, and chemotaxis and endothelial transmigration in a transwell model with an SDF-1α gradient. RESULTS: Here we show that both ABL/BCRs lost fundamental functional features of BCR regarding the regulation of small Rho-like GTPases with negative consequences on cell motility, in particular on the capacity to adhere to endothelial cells. CONCLUSION: Our data presented here describe for the first time an analysis of the biological function of the reciprocal t(9;22) ABL/BCR fusion proteins in comparison to their physiological counterpart BCR

AMPA Receptors Commandeer an Ancient Cargo Exporter for Use as an Auxiliary Subunit for Signaling

Fast excitatory neurotransmission in the mammalian central nervous system is mainly mediated by ionotropic glutamate receptors of the AMPA subtype (AMPARs). AMPARs are protein complexes of the pore-lining α-subunits GluA1-4 and auxiliary β-subunits modulating their trafficking and gating. By a proteomic approach, two homologues of the cargo exporter cornichon, CNIH-2 and CNIH-3, have recently been identified as constituents of native AMPARs in mammalian brain. In heterologous reconstitution experiments, CNIH-2 promotes surface expression of GluAs and modulates their biophysical properties. However, its relevance in native AMPAR physiology remains controversial. Here, we have studied the role of CNIH-2 in GluA processing both in heterologous cells and primary rat neurons. Our data demonstrate that CNIH-2 serves an evolutionarily conserved role as a cargo exporter from the endoplasmic reticulum (ER). CNIH-2 cycles continuously between ER and Golgi complex to pick up cargo protein in the ER and then to mediate its preferential export in a coat protein complex (COP) II dependent manner. Interaction with GluA subunits breaks with this ancestral role of CNIH-2 confined to the early secretory pathway. While still taking advantage of being exported preferentially from the ER, GluAs recruit CNIH-2 to the cell surface. Thus, mammalian AMPARs commandeer CNIH-2 for use as a bona fide auxiliary subunit that is able to modify receptor signaling

Expected Performance of the ATLAS Experiment - Detector, Trigger and Physics

A detailed study is presented of the expected performance of the ATLAS detector. The reconstruction of tracks, leptons, photons, missing energy and jets is investigated, together with the performance of b-tagging and the trigger. The physics potential for a variety of interesting physics processes, within the Standard Model and beyond, is examined. The study comprises a series of notes based on simulations of the detector and physics processes, with particular emphasis given to the data expected from the first years of operation of the LHC at CERN

Assessment of a continuous blood gas monitoring system in animals during circulatory stress

<p>Abstract</p> <p>Background</p> <p>The study was aimed to determine the measurement accuracy of The CDI™ blood parameter monitoring system 500 (Terumo Cardiovascular Systems Corporation, Ann Arbor MI) in the real-time continuous measurement of arterial blood gases under different cardiocirculatory stress conditions</p> <p>Methods</p> <p>Inotropic stimulation (Dobutamine 2.5 and 5 μg/kg/min), vasoconstriction (Arginine-vasopressin 4, 8 and 16 IU/h), hemorrhage (-10%, -20%, -35%, and -50% of the theoretical volemia), and volume resuscitation were induced in ten swine (57.4 ± 10.7 Kg).Intermittent blood gas assessments were carried out using a routine gas analyzer at any experimental phase and compared with values obtained at the same time settings during continuous monitoring with CDI™ 500 system. The Bland-Altman analysis was employed.</p> <p>Results</p> <p>Bias and precision for pO₂were - 0.06 kPa and 0.22 kPa, respectively (r²= 0.96); pCO₂- 0.02 kPa and 0.15 kPa, respectively; pH -0.001 and 0.01 units, respectively ( r²= 0.96). The analysis showed very good agreement for SO₂(bias 0.04,precision 0.33, r²= 0.95), Base excess (bias 0.04,precision 0.28, r²= 0.98), HCO₃(bias 0.05,precision 0.62, r²= 0.92),hemoglobin (bias 0.02,precision 0.23, r²= 0.96) and K⁺(bias 0.02, precision 0.27, r²= 0.93). The sensor was reliable throughout the experiment during hemodynamic variations.</p> <p>Conclusions</p> <p>Continuous blood gas analysis with the CDI™ 500 system was reliable and it might represent a new useful tool to accurately and timely monitor gas exchange in critically ill patients. Nonetheless, our findings need to be confirmed by larger studies to prove its reliability in the clinical setting.</p

Insulin Gene Expression Is Regulated by DNA Methylation

BACKGROUND:Insulin is a critical component of metabolic control, and as such, insulin gene expression has been the focus of extensive study. DNA sequences that regulate transcription of the insulin gene and the majority of regulatory factors have already been identified. However, only recently have other components of insulin gene expression been investigated, and in this study we examine the role of DNA methylation in the regulation of mouse and human insulin gene expression. METHODOLOGY/PRINCIPAL FINDINGS:Genomic DNA samples from several tissues were bisulfite-treated and sequenced which revealed that cytosine-guanosine dinucleotide (CpG) sites in both the mouse Ins2 and human INS promoters are uniquely demethylated in insulin-producing pancreatic beta cells. Methylation of these CpG sites suppressed insulin promoter-driven reporter gene activity by almost 90% and specific methylation of the CpG site in the cAMP responsive element (CRE) in the promoter alone suppressed insulin promoter activity by 50%. Methylation did not directly inhibit factor binding to the CRE in vitro, but inhibited ATF2 and CREB binding in vivo and conversely increased the binding of methyl CpG binding protein 2 (MeCP2). Examination of the Ins2 gene in mouse embryonic stem cell cultures revealed that it is fully methylated and becomes demethylated as the cells differentiate into insulin-expressing cells in vitro. CONCLUSIONS/SIGNIFICANCE:Our findings suggest that insulin promoter CpG demethylation may play a crucial role in beta cell maturation and tissue-specific insulin gene expression

MicroRNA-21 targets tumor suppressor genes ANP32A and SMARCA4

MicroRNA-21 (miR-21) is a key regulator of oncogenic processes. It is significantly elevated in the majority of human tumors and functionally linked to cellular proliferation, survival and migration. In this study, we used two experimental-based strategies to search for novel miR-21 targets. On the one hand, we performed a proteomic approach using two-dimensional differential gel electrophoresis (2D-DIGE) to identify proteins suppressed upon enhanced miR-21 expression in LNCaP human prostate carcinoma cells. The tumor suppressor acidic nuclear phosphoprotein 32 family, member A (ANP32A) (alias pp32 or LANP) emerged as the most strongly downregulated protein. On the other hand, we applied a mathematical approach to select correlated gene sets that are negatively correlated with primary-miR-21 (pri-miR-21) expression in published transcriptome data from 114 B-cell lymphoma cases. Among these candidates, we found tumor suppressor SMARCA4 (alias BRG1) together with the already validated miR-21 target, PDCD4. ANP32A and SMARCA4, which are both involved in chromatin remodeling processes, were confirmed as direct miR-21 targets by immunoblot analysis and reporter gene assays. Furthermore, knock down of ANP32A mimicked the effect of enforced miR-21 expression by enhancing LNCaP cell viability, whereas overexpression of ANP32A in the presence of high miR-21 levels abrogated the miR-21-mediated effect. In A172 glioblastoma cells, enhanced ANP32A expression compensated for the effects of anti-miR-21 treatment on cell viability and apoptosis. In addition, miR-21 expression clearly increased the invasiveness of LNCaP cells, an effect also seen in part upon downregulation of ANP32A. In conclusion, these results suggest that downregulation of ANP32A contributes to the oncogenic function of miR-21