International School for Advanced Studies

About: International School for Advanced Studies is a education organization based out in Trieste, Friuli-Venezia Giulia, Italy. It is known for research contribution in the topics: Galaxy & Dark matter. The organization has 3751 authors who have published 13433 publications receiving 588454 citations. The organization is also known as: SISSA & Scuola Internazionale Superiore di Studi Avanzati.

TMEM16B induces chloride currents activated by calcium in mammalian cells.

Abstract: Ca(2+)-activated Cl(-) channels play important physiological roles in various cell types, but their molecular identity is still unclear. Recently, members of the protein family named transmembrane 16 (TMEM16) have been suggested to function as Ca(2+)-activated Cl(-) channels. Here, we report the functional properties of mouse TMEM16B (mTMEM16B) expressed in human embryonic kidney (HEK) 293T cells, measured both in the whole-cell configuration and in inside-out excised patches. In whole cell, a current induced by mTMEM16B was activated by intracellular Ca(2+) diffusing from the patch pipette, released from intracellular stores through activation of a G-protein-coupled receptor, or photoreleased from caged Ca(2+) inside the cell. In inside-out membrane patches, a current was rapidly activated by bath application of controlled Ca(2+) concentrations, indicating that mTMEM16B is directly gated by Ca(2+). Both in the whole-cell and in the inside-out configurations, the Ca(2+)-induced current was anion selective, blocked by the Cl(-) channel blocker niflumic acid, and displayed a Ca(2+)-dependent rectification. In inside-out patches, Ca(2+) concentration for half-maximal current activation decreased from 4.9 microM at -50 mV to 3.3 microM at +50 mV, while the Hill coefficient was >2. In inside-out patches, currents showed a reversible current decrease at -50 mV in the presence of a constant high Ca(2+) concentration and, moreover, an irreversible rundown, not observed in whole-cell recordings, indicating that some unknown modulator was lost upon patch excision. Our results demonstrate that mTMEM16B functions as a Ca(2+)-activated Cl(-) channel when expressed in HEK 293T cells.

Cosmology with massive neutrinos II: on the universality of the halo mass function and bias

Abstract: We use a large suite of N-body simulations to study departures from universality in halo abundances and clustering in cosmologies with non-vanishing neutrino masses. To this end, we study how the halo mass function and halo bias factors depend on the scaling variable σ2(M,z), the variance of the initial matter fluctuation field, rather than on halo mass M and redshift z themselves. We show that using the variance of the cold dark matter rather than the total mass field, i.e., σ2cdm(M,z) rather than σ2m(M,z), yields more universal results. Analysis of halo bias yields similar conclusions: when large-scale halo bias is defined with respect to the cold dark matter power spectrum, the result is both more universal, and less scale- or k-dependent. These results are used extensively in Papers I and III of this series.

Interacting Individuals Leading to Zipf's Law

Abstract: We present a general approach to explain the Zipf's law of city distribution. If the simplest interaction (pairwise) is assumed, individuals tend to form cities in agreement with the well-known statistics.

Receptor for Advanced Glycation End Product-Dependent Activation of p38 Mitogen-Activated Protein Kinase Contributes to Amyloid-β-Mediated Cortical Synaptic Dysfunction

Abstract: Soluble amyloid-β (Aβ) peptide is likely to play a key role during early stages of Alzheimer's disease (AD) by perturbing synaptic function and cognitive processes. Receptor for advanced glycation end products (RAGE) has been identified as a receptor involved in Aβ-induced neuronal dysfunction. We investigated the role of neuronal RAGE in Aβ-induced synaptic dysfunction in the entorhinal cortex, an area of the brain important in memory processes that is affected early in AD. We found that soluble oligomeric Aβ peptide (Aβ42) blocked long-term potentiation (LTP), but did not affect long-term depression, paired-pulse facilitation, or basal synaptic transmission. In contrast, Aβ did not inhibit LTP in slices from RAGE-null mutant mice or in slices from wild-type mice treated with anti-RAGE IgG. Similarly, transgenic mice expressing a dominant-negative form of RAGE targeted to neurons showed normal LTP in the presence of Aβ, suggesting that neuronal RAGE functions as a signal transducer for Aβ-mediated LTP impairment. To investigate intracellular pathway transducing RAGE activation by Aβ, we used inhibitors of stress activated kinases. We found that inhibiting p38 mitogen-activated protein kinase (p38 MAPK), but not blocking c-Jun N-terminal kinase activation, was capable of maintaining LTP in Aβ-treated slices. Moreover, Aβ-mediated enhancement of p38 MAPK phosphorylation in cortical neurons was reduced by blocking antibodies to RAGE. Together, our results indicate that Aβ impairs LTP in the entorhinal cortex through neuronal RAGE-mediated activation of p38 MAPK.