914 research outputs found

    Molecular Electroporation and the Transduction of Oligoarginines

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    Certain short polycations, such as TAT and polyarginine, rapidly pass through the plasma membranes of mammalian cells by an unknown mechanism called transduction as well as by endocytosis and macropinocytosis. These cell-penetrating peptides (CPPs) promise to be medically useful when fused to biologically active peptides. I offer a simple model in which one or more CPPs and the phosphatidylserines of the inner leaflet form a kind of capacitor with a voltage in excess of 180 mV, high enough to create a molecular electropore. The model is consistent with an empirical upper limit on the cargo peptide of 40--60 amino acids and with experimental data on how the transduction of a polyarginine-fluorophore into mouse C2C12 myoblasts depends on the number of arginines in the CPP and on the CPP concentration. The model makes three testable predictions.Comment: 15 pages, 5 figure

    Identification of motifs that function in the splicing of non-canonical introns

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    The enrichment of specific intronic splicing enhancers upstream of weak PY tracts suggests a novel mechanism for intron recognition that compensates for a weakened canonical pre-mRNA splicing motif

    Palaeoclimatic events, dispersal and migratory losses along the Afro-European axis as drivers of biogeographic distribution in Sylvia warblers

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    <p>Abstract</p> <p>Background</p> <p>The Old World warbler genus <it>Sylvia </it>has been used extensively as a model system in a variety of ecological, genetic, and morphological studies. The genus is comprised of about 25 species, and 70% of these species have distributions at or near the Mediterranean Sea. This distribution pattern suggests a possible role for the Messinian Salinity Crisis (from 5.96-5.33 Ma) as a driving force in lineage diversification. Other species distributions suggest that Late Miocene to Pliocene Afro-tropical forest dynamics have also been important in the evolution of <it>Sylvia </it>lineages. Using a molecular phylogenetic hypothesis and other methods, we seek to develop a biogeographic hypothesis for <it>Sylvia </it>and to explicitly assess the roles of these climate-driven events.</p> <p>Results</p> <p>We present the first strongly supported molecular phylogeny for <it>Sylvia</it>. With one exception, species fall into one of three strongly supported clades: one small clade of species distributed mainly in Africa and Europe, one large clade of species distributed mainly in Africa and Asia, and another large clade with primarily a circum-Mediterranean distribution. Asia is reconstructed as the ancestral area for <it>Sylvia</it>. Long-distance migration is reconstructed as the ancestral character state for the genus, and sedentary behavior subsequently evolved seven times.</p> <p>Conclusion</p> <p>Molecular clock calibration suggests that <it>Sylvia </it>arose in the early Miocene and diverged into three main clades by 12.6 Ma. Divergence estimates indicate that the Messinian Salinity Crisis had a minor impact on <it>Sylvia</it>. Instead, over-water dispersals, repeated loss of long-distance migration, and palaeo-climatic events in Africa played primary roles in <it>Sylvia </it>divergence and distribution.</p

    Modeling of Surface Damage at the Si/SiO2_2-interface of Irradiated MOS-capacitors

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    Surface damage caused by ionizing radiation in SiO2_2 passivated silicon particle detectors consists mainly of the accumulation of a positively charged layer along with trapped-oxide-charge and interface traps inside the oxide and close to the Si/SiO2_2-interface. High density positive interface net charge can be detrimental to the operation of a multi-channel nn-on-pp sensor since the inversion layer generated under the Si/SiO2_2-interface can cause loss of position resolution by creating a conduction channel between the electrodes. In the investigation of the radiation-induced accumulation of oxide charge and interface traps, a capacitance-voltage characterization study of n/γ\gamma- and γ\gamma-irradiated Metal-Oxide-Semiconductor (MOS) capacitors showed that close agreement between measurement and simulation were possible when oxide charge density was complemented by both acceptor- and donor-type deep interface traps with densities comparable to the oxide charges. Corresponding inter-strip resistance simulations of a nn-on-pp sensor with the tuned oxide charge density and interface traps show close agreement with experimental results. The beneficial impact of radiation-induced accumulation of deep interface traps on inter-electrode isolation may be considered in the optimization of the processing parameters of isolation implants on nn-on-pp sensors for the extreme radiation environments.Comment: Corresponding author: T. Peltola. 24 pages, 17 figures, 6 table

    Isolation and Characterization of the Saccharomyces cerevisiae DPP1 Gene Encoding Diacylglycerol Pyrophosphate Phosphatase

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    Diacylglycerol pyrophosphate (DGPP) is involved in a putative novel lipid signaling pathway. DGPP phosphatase (DGPP phosphohydrolase) is a membrane-associated 34-kDa enzyme fromSaccharomyces cerevisiae which catalyzes the dephosphorylation of DGPP to yield phosphatidate (PA) and then catalyzes the dephosphorylation of PA to yield diacylglycerol. Amino acid sequence information derived from DGPP phosphatase was used to identify and isolate the DPP1(diacylglycerol pyrophosphatephosphatase) gene encoding the enzyme. Multicopy plasmids containing the DPP1 gene directed a 10-fold overexpression of DGPP phosphatase activity in S. cerevisiae. The heterologous expression of the S. cerevisiae DPP1 gene in Sf-9 insect cells resulted in a 500-fold overexpression of DGPP phosphatase activity over that expressed in wild-type S. cerevisiae. DGPP phosphatase possesses a Mg2+-independent PA phosphatase activity, and its expression correlated with the overexpression of DGPP phosphatase activity in S. cerevisiae and in insect cells. DGPP phosphatase was predicted to be an integral membrane protein with six transmembrane-spanning domains. The enzyme contains a novel phosphatase sequence motif found in a superfamily of phosphatases. Adpp1Δ mutant was constructed by deletion of the chromosomal copy of the DPP1 gene. The dpp1Δ mutant was viable and did not exhibit any obvious growth defects. The mutant was devoid of DGPP phosphatase activity and accumulated (4-fold) DGPP. Analysis of the mutant showed that the DPP1 gene was not responsible for all of the Mg2+-independent PA phosphatase activity in S. cerevisiae

    Theory of d-density wave viewed from a vertex model and its implications

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    The thermal disordering of the dd-density wave, proposed to be the origin of the pseudogap state of high temperature superconductors, is suggested to be the same as that of the statistical mechanical model known as the 6-vertex model. The low temperature phase consists of a staggered order parameter of circulating currents, while the disordered high temperature phase is a power-law phase with no order. A special feature of this transition is the complete lack of an observable specific heat anomaly at the transition. There is also a transition at a even higher temperature at which the magnitude of the order parameter collapses. These results are due to classical thermal fluctuations and are entirely unrelated to a quantum critical point in the ground state. The quantum mechanical ground state can be explored by incorporating processes that causes transitions between the vertices, allowing us to discuss quantum phase transition in the ground state as well as the effect of quantum criticality at a finite temperature as distinct from the power-law fluctuations in the classical regime. A generalization of the model on a triangular lattice that leads to a 20-vertex model may shed light on the Wigner glass picture of the metal-insulator transition in two-dimensional electron gas. The power-law ordered high temperature phase may be generic to a class of constrained systems and its relation to recent advances in the quantum dimer models is noted.Comment: RevTex4, 10 pages, 11 figure
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