4,606 research outputs found

    Charybdotoxin binding in the I(Ks) pore demonstrates two MinK subunits in each channel complex.

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    I(Ks) voltage-gated K(+) channels contain four pore-forming KCNQ1 subunits and MinK accessory subunits in a number that has been controversial. Here, I(Ks) channels assembled naturally by monomer subunits are compared to those with linked subunits that force defined stoichiometries. Two strategies that exploit charybdotoxin (CTX)-sensitive subunit variants are applied. First, CTX on rate, off rate, and equilibrium affinity are found to be the same for channels of monomers and those with a fixed 2:4 MinK:KCNQ1 valence. Second, 3H-CTX and an antibody are used to directly quantify channels and MinK subunits, respectively, showing 1.97 +/- 0.07 MinK per I(Ks) channel. Additional MinK subunits do not enter channels of monomeric subunits or those with fixed 2:4 valence. We conclude that two MinK subunits are necessary, sufficient, and the norm in I(Ks) channels. This stoichiometry is expected for other K(+) channels that contain MinK or MinK-related peptides (MiRPs)

    Structure and Aggregation of a Helix-Forming Polymer

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    We have studied the competition between helix formation and aggregation for a simple polymer model. We present simulation results for a system of two such polymers, examining the potential of mean force, the balance between inter and intramolecular interactions, and the promotion or disruption of secondary structure brought on by the proximity of the two molecules. In particular, we demonstrate that proximity between two such molecules can stabilize secondary structure. However, for this model, observed secondary structure is not stable enough to prevent collapse of the system into an unstructured globule.Comment: Accepted to the Journal of Chemical Physic

    Advances in Materials and Technologies for Gas Sensing from Environmental and Food Monitoring to Breath Analysis

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    Gas sensing research experiences a worldwide revival in the last years. From one side, the emergence of novel sensing materials enables unprecedented capacities for improving the device performances. From the other, the increasing opportunities for applications impacting current societal priorities highly motivate further studies. Here, this field is reviewed with special attention to the emerging approaches and the most recent breakthroughs, challenges, and perspectives. In particular, this study focuses on: 1) the sensing layers analyzing recent trends toward nanostructured, low-dimensional and composite materials; and 2) the latest achievements and targets in terms of applications, from environmental monitoring to food aroma identification and quality control up to the healthcare sector with breath analysis and diseases diagnosis

    Carcinomas of Distal Fallopian Tube and Their Association with Tubal Intraepithelial Carcinoma: Do They Share a Common “Precursor” Lesion? Loss of Heterozygosity and Immunohistochemical Analysis Using PAX 2, WT-1, and P53 Markers

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    As the role of distal fallopian tube as organ of serous carcinogenesis is emerging, additional literature on the role of tubal intraepithelial carcinoma (TIC) as a precursor lesion in a subset of primary peritoneal serous carcinomas (PPSC is emerging as well. TIC although fallopian tube in origin can be genetically related to ovarian/peritoneal carcinomas. The role of PAX2 in primary fallopian tube carcinomas (PFTC)/PPSC is yet to be defined. The aim of our study was to understand if the biologic properties of tumors arising in the distal fallopian tube that remain as PFTC are different when they seed on to the peritoneal surface (PPSC). A panel of 6 polymorphic microsatellite markers corresponding to p53, PAX2, and WT1 tumor suppressor genes were studied. Invasive carcinomas as well as TIC arising in the distal fallopian tube when remain as PFTC appears to exhibit different LOH patterns in comparison to PPSC. PAX 2 LOH patterns might represent a “hidden PAX 2 signature” analogous to p53 signatures. PAX 2 might be an emerging marker for detection of early serous carcinomas particularly in BRCA + women

    Cooperative Carbon Dioxide Adsorption in Alcoholamine- and Alkoxyalkylamine-Functionalized Metal-Organic Frameworks.

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    A series of structurally diverse alcoholamine- and alkoxyalkylamine-functionalized variants of the metal-organic framework Mg2 (dobpdc) are shown to adsorb CO2 selectively via cooperative chain-forming mechanisms. Solid-state NMR spectra and optimized structures obtained from van der Waals-corrected density functional theory calculations indicate that the adsorption profiles can be attributed to the formation of carbamic acid or ammonium carbamate chains that are stabilized by hydrogen bonding interactions within the framework pores. These findings significantly expand the scope of chemical functionalities that can be utilized to design cooperative CO2 adsorbents, providing further means of optimizing these powerful materials for energy-efficient CO2 separations

    A Qualitative Ethnographic Case Study Exploring the Hispanic/Latinx Interpretations of Collegiate Aviation Safety Culture

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    Through a combination of ethnographic principles and a qualitative case study structure, this study strives to understand how Hispanic/ Latinx aviation students perceive the current aviation safety culture in their flight training program. Grounded in the reciprocal safety culture model, the researchers attempt to answer how does Hispanic/Latinx culture influence perceptions towards commitment to aviation safety? and what are Hispanic/Latinx students’ perceptions of their ability to influence aviation safety culture? Three major themes emerged from the data: behavioral signs of safety culture at the collegiate level, obstacles to a sound safety culture, and methods to improve the safety culture. Moreover, factors such as individualism, masculinity, access to economic resources, and language were prevalent in the findings on how Hispanic aviation students perceive their collegiate flight training safety culture. Future studies should explore the perception of different ethnic groups of aviation students at various geographical locations to identify any added layers of threat, behavioral attitudes, and safety compromises related to flight training

    Three-Dimensional Structure of Ito Kv4.2-KChIP2 Ion Channels by Electron Microscopy at 21 Å Resolution

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    AbstractRegulatory KChIP2 subunits assemble with pore-forming Kv4.2 subunits in 4:4 complexes to produce native voltage-gated potassium (Kv) channels like cardiac Ito and neuronal IA subtypes. Here, negative stain electron microscopy (EM) and single particle averaging reveal KChIP2 to create a novel ∼35 × 115 × 115 Å, intracellular fenestrated rotunda: four peripheral columns that extend down from the membrane-embedded portion of the channel to enclose the Kv4.2 “hanging gondola” (a platform held beneath the transmembrane conduction pore by four internal columns). To reach the pore from the cytosol, ions traverse one of four external fenestrae to enter the rotundal vestibule and then cross one of four internal windows in the gondola
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