Revisit of the Cardiac Inward Rectifier Potassium Current IK1

Inward rectifier potassium currents are present in different types of cells. In the heart, the inward rectifier potassium current IK1 plays a crucial role in maintaining cardiac resting membrane potential and excitability. It is generally believed that the strong inward rectification of cardiac IK1 channels makes it conduct substantial current near the resting potential but carry little or no current at depolarized potentials. However, recent studies in native cardiac myocytes and HEK 293 cell line stably expressing human Kir2.1 gene have demonstrated that a significant transient outward current carried by IK1 channels is activated by the upstroke of action potential. This review will revisit cardiac IK1 channels, especially the previously-ignored transient outward component of IK1 carried by Kir2.1 channels.published_or_final_versio

Regulation of human cardiac KCNQ1/KCNE1 channel by epidermal growth factor receptor kinase

The aim of the present study was to investigate whether/how the recombinant human cardiac I Ks could be regulated by epidermal growth factor receptor kinase in HEK 293 cells stably expressing hKCNQ1/hKCNE1 genes using the approaches of perforated patch clamp technique, immunoprecipitation and Western blot analysis. It was found that the broad spectrum isoflavone tyrosine kinase inhibitor genistein and the selective epidermal growth factor receptor kinase inhibitor tyrphostin AG556 suppressed the recombinant I Ks, and their inhibition was countered by the protein tyrosine phosphatase inhibitor orthovanadate. The Src-family kinase inhibitor PP2 reduced the current, but the effect was not antagonized by orthovanadate. Immunoprecipitation and Western blot analysis revealed that tyrosine phosphorylation level of hKCNQ1 protein was decreased by genistein or AG556, but not by PP2. These results provide the novel information that epidermal growth factor receptor kinase, but not Src-family kinases, regulates the recombinant cardiac I Ks stably expressed in HEK 293 cells via phosphorylating KCNQ1 protein of the channel. © 2009 Elsevier B.V. All rights reserved.postprin

Human ether-à-go-go gene potassium channels are regulated by EGFR tyrosine kinase

Human ether á-go-go gene potassium channels (hEAG1 or Kv10.1) are expressed in brain and various human cancers and play a role in neuronal excitement and tumor progression. However, the functional regulation of hEAG channels by signal transduction is not fully understood. The present study was therefore designed to investigate whether hEAG1 channels are regulated by protein tyrosine kinases (PTKs) in HEK 293 cells stably expressing hEAG1 gene using whole-cell patch voltage-clamp, immunoprecipitation, Western blot, and mutagenesis approaches. We found that the selective epidermal growth factor receptor (EGFR) kinase inhibitor AG556 (10μM), but not the platelet growth factor receptor (PDGFR) kinase inhibitor AG1295 (10μM) or the Src-family inhibitor PP2 (10μM), can inhibit hEAG1 current, and the inhibitory effect can be reversed by the protein tyrosine phosphatase (PTP) inhibitor orthovanadate. Immunoprecipitation and Western blot analysis revealed that tyrosine phosphorylation level of hEAG1 channels was reduced by AG556, and the reduction was significantly countered by orthovanadate. The hEAG1 mutants Y90A, Y344A and Y485A, but not Y376A and Y479A, exhibited reduced response to AG556. Interestingly, the inhibition effect of AG556 was lost in triple mutant hEAG1 channels at Y90, Y344, and Y485 with alanine. These results demonstrate for the first time that hEAG1 channel activity is regulated by EGFR kinase at the tyrosine residues Tyr 90, Try 344, and Try 485. This effect is likely involved in regulating neuronal activity and/or tumor growth. © 2011 Elsevier B.V.postprin

Deep Markov Random Field for Image Modeling

Markov Random Fields (MRFs), a formulation widely used in generative image modeling, have long been plagued by the lack of expressive power. This issue is primarily due to the fact that conventional MRFs formulations tend to use simplistic factors to capture local patterns. In this paper, we move beyond such limitations, and propose a novel MRF model that uses fully-connected neurons to express the complex interactions among pixels. Through theoretical analysis, we reveal an inherent connection between this model and recurrent neural networks, and thereon derive an approximated feed-forward network that couples multiple RNNs along opposite directions. This formulation combines the expressive power of deep neural networks and the cyclic dependency structure of MRF in a unified model, bringing the modeling capability to a new level. The feed-forward approximation also allows it to be efficiently learned from data. Experimental results on a variety of low-level vision tasks show notable improvement over state-of-the-arts.Comment: Accepted at ECCV 201

Filipina American women's breast cancer knowledge, attitudes, and screening behaviors

BACKGROUND: Filipino Americans are the fastest growing Asian minority group in the United States. There is limited knowledge about their breast cancer knowledge, screening practices and attitudes. METHODS: As part of the evaluation of the Asian Grocery Store-Based Cancer Education Program, 248 Filipino American women completed baseline and follow-up surveys, while an additional 58 took part in focus groups. RESULTS: Compliance with annual clinical breast exam guidelines among women 40 to 49 years old was 43%, and annual mammography use among women 50 and over was 56%. The Asian Grocery Store-Based Cancer Education Program and complementary focus group study identified multiple barriers that hindered women from attending education programs, with time as the most frequently reported barrier. CONCLUSION: The Asian Grocery Store-Based Cancer Education Program was reported to be a culturally acceptable and effective way of disseminating breast cancer information and one that addressed the women's most frequently reported barrier, lack of time

Anisotropic Structure of the Order Parameter in FeSe0.45Te0.55 Revealed by Angle Resolved Specific Heat

The symmetry and structure of the superconducting gap in the Fe-based superconductors are the central issue for understanding these novel materials. So far the experimental data and theoretical models have been highly controversial. Some experiments favor two or more constant or nearly-constant gaps, others indicate strong anisotropy and yet others suggest gap zeros ("nodes"). Theoretical models also vary, suggesting that the absence or presence of the nodes depends quantitatively on the model parameters. An opinion that has gained substantial currency is that the gap structure, unlike all other known superconductors, including cuprates, may be different in different compounds within the same family. A unique method for addressing this issue, one of the very few methods that are bulk and angle-resolved, calls for measuring the electronic specific heat in a rotating magnetic field, as a function of field orientation with respect to the crystallographic axes. In this Communication we present the first such measurement for an Fe-based high-Tc superconductor (FeBSC). We observed a fourfold oscillation of the specific heat as a function of the in-plane magnetic field direction, which allowed us to identify the locations of the gap minima (or nodes) on the Fermi surface. Our results are consistent with the expectations of an extended s-wave model with a significant gap anisotropy on the electron pockets and the gap minima along the \Gamma M (or Fe-Fe bond) direction.Comment: 32 pages, 7 figure

Prognostic relevance of a T-type calcium channels gene signature in solid tumours: A correlation ready for clinical validation

BackgroundT-type calcium channels (TTCCs) mediate calcium influx across the cell membrane. TTCCs regulate numerous physiological processes including cardiac pacemaking and neuronal activity. In addition, they have been implicated in the proliferation, migration and differentiation of tumour tissues. Although the signalling events downstream of TTCC-mediated calcium influx are not fully elucidated, it is clear that variations in the expression of TTCCs promote tumour formation and hinder response to treatment.MethodsWe examined the expression of TTCC genes (all three subtypes; CACNA-1G, CACNA-1H and CACNA-1I) and their prognostic value in three major solid tumours (i.e. gastric, lung and ovarian cancers) via a publicly accessible database.ResultsIn gastric cancer, expression of all the CACNA genes was associated with overall survival (OS) among stage I-IV patients (all pConclusionsAlterations in CACNA gene expression are linked to tumour prognosis. Gastric cancer represents the most promising setting for further evaluation

Dzyaloshinskii-Moriya Interaction and Spiral Order in Spin-orbit Coupled Optical Lattices

We show that the recent experimental realization of spin-orbit coupling in ultracold atomic gases can be used to study different types of spin spiral order and resulting multiferroic effects. Spin-orbit coupling in optical lattices can give rise to the Dzyaloshinskii-Moriya (DM) spin interaction which is essential for spin spiral order. By taking into account spin-orbit coupling and an external Zeeman field, we derive an effective spin model in the Mott insulator regime at half filling and demonstrate that the DM interaction in optical lattices can be made extremely strong with realistic experimental parameters. The rich finite temperature phase diagrams of the effective spin models for fermions and bosons are obtained via classical Monte Carlo simulations.Comment: 7 pages, 5 figure

FTO gene SNPs associated with extreme obesity in cases, controls and extremely discordant sister pairs

<p>Abstract</p> <p>Background</p> <p>FTO is a gene located in chromosome region 16q12.2. Recently two studies have found associations of several single nucleotide polymorphisms (SNPs) in FTO with body mass index (BMI) and obesity, particularly rs1421085, rs17817449, and rs9939609.</p> <p>Methods</p> <p>We examined these three SNPs in 583 extremely obese women with current BMI greater than 35 kg/m²and lifetime BMI greater than 40 kg/m², and 544 controls who were currently normal weight (BMI<25 kg/m²) and had never been overweight during their lifetimes.</p> <p>Results</p> <p>We detected highly significant associations of obesity with alleles in all three SNPs (p < 10^-9). The strongest association was with rs1421085 (p = 3.04 × 10^-10, OR = 1.75, CI = 1.47–2.08). A subset of 99 cases had extremely discordant sisters with BMI<25 kg/m². The discordant sisters differed in allele and genotype frequencies in parallel with the overall case and control sample. The strongest association was with rs17817449 (z = 3.57, p = 3.6 × 10^-4).</p> <p>Conclusion</p> <p>These results suggest common variability in FTO is associated with increased obesity risk or resistance and may in part account for differences between closely related individuals.</p

Mega-blowouts in Qinghai–Tibet Plateau: morphology, distribution and initiation.

Blowouts are wind‐eroded landforms that are widely distributed in the north‐eastern part in Qinghai–Tibet Plateau (QTP), China. These blowouts are thought to form in response to climate change and/or human activity but little is known about their morphodynamics. Using field surveys, remote sensing and geographic information system (GIS) spatial analysis, the distribution and morphology of blowouts are analysed and their initiation considered. Results show the QTP mega‐blowouts are some of the largest in the world. The orientations of the trough shaped blowouts are parallel with the prevailing wind, but the saucer and bowl‐shaped blowouts are influenced by bi‐directional transport. Whilst regional patterns of blowout shape and size were observed to reflect the extent of aeolian sediments and wind regimes, the relationship between the different morphological parameters showed consistency. During initial stages of development, the length to width ratios of blowouts increase rapidly with area but after they reach a mega size this relationship stabilizes as blowouts widen. Initial luminescence dating shows that blowouts appear to have initiated ~100 to 500 years ago, coinciding with the Little Ice Age (LIA) climate event when northwest winds are known to have intensified. Further work is required to confirm this initiation period and establish the significance of mega blowouts for landscape degradation and human activities