Epidermal Growth Factor Stimulates Cell Proliferation by Activating Voltage-Gated Potassium Channels in Rat Bone Marrow-Derived Mesenchymal Stem Cells

Poster PresentationBackground and objective: We have previously found that voltage-gated delayed rectifier potassium current (IKDR, encoded by Kv1.2 and Kv2.1) participated in regulation of cell cycling progression in rat mesenchymal stem cells (MSCs) from bone marrow. The present study was designed to investigate whether epidermal growth factor (EGF) regulates cell growth is mediated by activating IKDR. Methods: Whole-cell patch voltage-clamp, RT-PCR, Western blots, siRNA, cell proliferation assay were employed in the present study Results: EGF increased cell proliferation in a concentration-dependent manner, and the effect was countered by the broad spectrum protein tyrosine (PTK) inhibitor genistein and the EGFR kinase inhibitor AG556. We found that genistein and AG556 inhibited IKDR in a concentration-dependent manner, The protein tyrosine phosphatase (PTP) inhibitor orthovanadate enhanced IKDR, and counted the inhibitory effect of IKDR by genistein or AG556, suggesting the PTK-mediating modulation of IKDR. Interestingly EGF also increased IKDR, Downregulation of IKDR with siRNA targeting to Kv1.2 or Kv2.1 channels inhibited basal proliferation, and prevented EGF-stimulated proliferation in rat MSCs. Conclusion: These results demonstrate for the first time that EGF stimulates cell proliferation activating IKDR, and silencing Kv1.2 or Kv2.1 channels prevents the augmentation of proliferation by EFG, indicating that Kv1.2 and Kv2.1 channels mediate EGF effect in regulating cell growth in rat MSCs.published_or_final_versio

EGFR Tyrosine kinase regulates small conductance Ca2+-activated K+ (hSKCa1) channels expressed in HEK 293 cells

SKCa (small-conductance Ca(2+)-activated K(+)) channels are widely distributed in different tissues, including the brain, pancreatic islets and myocardium and play an important role in controlling electrical activity and cellular functions. However, intracellular signal modulation of SKCa channels is not fully understood. The present study was designed to investigate the potential regulation of hSKCa1 (human SKCa1) channels by PTKs (protein tyrosine kinases) in HEK (human embryonic kidney)-293 cells expressing the hSKCa1 (KCNN1) gene using approaches of whole-cell patch voltage-clamp, immunoprecipitation, Western blotting and mutagenesis. We found that the hSKCa1 current was inhibited by the broad-spectrum PTK inhibitor genistein, the selective EGFR (epidermal growth factor receptor) kinase inhibitors T25 (tyrphostin 25) and AG556 (tyrphostin AG 556), but not by the Src-family kinases inhibitor PP2. The inhibitory effect of these PTK inhibitors was significantly antagonized by the PTP (protein tyrosine phosphatase) inhibitor orthovanadate. The tyrosine phosphorylation level of hSKCa1 channels was reduced by genistein, T25 or AG556. The reduced tyrosine phosphorylation was countered by orthovanadate. Interestingly, the Y109F mutant hSKCa1 channel lost the inhibitory response to T25 or AG556, and showed a dramatic reduction in tyrosine phosphorylation levels and a reduced current density. These results demonstrate the novel information that hSKCa1 channels are inhibited by genistein, T25 and AG556 via EGFR tyrosine kinase inhibition, which is related to the phosphorylation of Tyr(109) in the N-terminus. This effect may affect electrical activity and cellular functions in brain, pancreatic islets and myocardium.postprin

On the Application of a Monolithic Array for Detecting Intensity-Correlated Photons Emitted by Different Source Types

It is not widely appreciated that many subtleties are involved in the accurate measurement of intensity-correlated photons; even for the original experiments of Hanbury Brown and Twiss (HBT). Using a monolithic 4x4 array of single-photon avalanche diodes (SPADs), together with an off-chip algorithm for processing streaming data, we investigate the difficulties of measuring second-order photon correlations g2 in a wide variety of light fields that exhibit dramatically different correlation statistics: a multimode He-Ne laser, an incoherent intensity-modulated lamp-light source and a thermal light source. Our off-chip algorithm treats multiple photon-arrivals at pixel-array pairs, in any observation interval, with photon fluxes limited by detector saturation, in such a way that a correctly normalized g2 function is guaranteed. The impact of detector background correlations between SPAD pixels and afterpulsing effects on second-order coherence measurements is discussed. These results demonstrate that our monolithic SPAD array enables access to effects that are otherwise impossible to measure with stand-alone detectors.Comment: 17 pages, 6 figure

Modulation of human cardiac transient outward potassium current by EGFR tyrosine kinase and Src-family kinases

Aims: The human cardiac transient outward K + current Ito (encoded by Kv4.3 or KCND3) plays an important role in phase 1 rapid repolarization of cardiac action potentials in the heart. However, modulation of I to by intracellular signal transduction is not fully understood. The present study was therefore designed to determine whether/how human atrial I to and hKv4.3 channels stably expressed in HEK 293 cells are regulated by protein tyrosine kinases (PTKs). Methods and results: Whole-cell patch voltage-clamp, immunoprecipitation, western blotting, and site-directed mutagenesis approaches were employed in the present study. We found that human atrial I to was inhibited by the broad-spectrum PTK inhibitor genistein, the selective epidermal growth factor receptor (EGFR) kinase inhibitor AG556, and the Src-family kinases inhibitor PP2. The inhibitory effect was countered by the protein tyrosine phosphatase inhibitor orthovanadate. In HEK 293 cells stably expressing human KCND3, genistein, AG556, and PP2 significantly reduced the hKv4.3 current, and the reduction was antagonized by orthovanadate. Interestingly, orthovanadate also reversed the reduced tyrosine phosphorylation level of hKv4.3 channels by genistein, AG556, or PP2. Mutagenesis revealed that the hKv4.3 mutant Y136F lost the inhibitory response to AG556, while Y108F lost response to PP2. The double-mutant Y108FY136F hKv4.3 channels showed no response to either AG556 or PP2. Conclusion: Our results demonstrate that human atrial Ito and cloned hKv4.3 channels are modulated by EGFR kinase via phosphorylation of the Y136 residue and by Src-family kinases via phosphorylation of the Y108 residue; tyrosine phosphorylation of the channel may be involved in regulating cardiac electrophysiology. © The Author 2011.postprin

Allitridi Inhibits Multiple Cardiac Potassium Channels Expressed in HEK 293 Cells

published_or_final_versio

A comparative evaluation of dried activated sludge and mixed dried activated sludge with rice husk silica to remove hydrogen sulfide.

The aim of this study was to investigate the effectiveness of dried activated sludge (DAS) and mixed dried activated sludge with rice husk silica (DAS & RHS) for removal of hydrogen sulfide (H2S). Two laboratory-scale filter columns (packed one litter) were operated. Both systems were operated under different conditions of two parameters, namely different inlet gas concentrations and different inlet flow rates. The DAS & RHS packed filter showed more than 99.96% removal efficiency (RE) with empty bed residence time (EBRT) of 45 to 90 s and 300 mg/L inlet concentration of H2S. However, the RE decreased to 96.87% with the EBRT of 30 s. In the same condition, the DAS packed filter showed 99.37% RE. Nonetheless, the RE was shown to have dropped to 82.09% with the EBRT of 30 s. The maximum elimination capacity (EC) was obtained in the DAS & RHS packed filter up to 52.32 g/m3h, with the RE of 96.87% and H2S mass loading rate of 54 g/m3h. The maximum EC in the DAS packed filter was obtained up to 44.33 g/m3h with the RE of 82.09% and the H2S mass loading rate of 54 g/m3h. After 53 days of operating time and 54 g/m3h of loading rates, the maximum pressure drop reached to 3.0 and 8.0 (mm H2O) for the DAS & RHS packed and DAS packed filters, respectively. Based on the findings of this study, the DAS & RHS could be considered as a more suitable packing material to remove H2S

Disparities and risks of sexually transmissible infections among men who have sex with men in China: a meta-analysis and data synthesis.

BACKGROUND: Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. METHODS: Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. RESULTS: Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia, 1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8-10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4-74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. CONCLUSION: Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. TRIAL REGISTRATION: PROSPERO NO: CRD42013003721

QTLs for height: results of a full genome scan in Dutch sibling pairs.

Height is a highly heritable, complex trait. At present, the genes responsible for the variation in height have not yet been identified. This paper summarizes the results of previous linkage studies and presents results of an additional linkage analysis. Using data from the Netherlands Twin Register, a sib-pair-based linkage analysis for adult height was conducted. For 513 sib-pairs from 174 families complete genome scans and adult height were available. The strongest evidence for linkage was found for a region on chromosome 6, near markers D6S1053 and D6S1031 (LOD = 2.32). This replicated previous findings in other data sets. LOD scores ranging from 1.53 to 2.04 were found for regions on chromosomes 1, 5, 8, 10, and 18. The region on chromosome 18 (LOD = 1.83) also corresponded with the results of previous studies. Several chromosomal regions are now implied in the variance in height, but further study is needed to draw definite conclusions with regard to the significance of these regions for adult heigh

Tailoring force sensitivity and selectivity by microstructure engineering of multidirectional electronic skins

Electronic skins (e-skins) with high sensitivity to multidirectional mechanical stimuli are crucial for healthcare monitoring devices, robotics, and wearable sensors. In this study, we present piezoresistive e-skins with tunable force sensitivity and selectivity to multidirectional forces through the engineered microstructure geometries (i.e., dome, pyramid, and pillar). Depending on the microstructure geometry, distinct variations in contact area and localized stress distribution are observed under different mechanical forces (i.e., normal, shear, stretching, and bending), which critically affect the force sensitivity, selectivity, response/relaxation time, and mechanical stability of e-skins. Microdome structures present the best force sensitivities for normal, tensile, and bending stresses. In particular, microdome structures exhibit extremely high pressure sensitivities over broad pressure ranges (47,062 kPa(-1) in the range of < 1 kPa, 90,657 kPa(-1) in the range of 1-10 kPa, and 30,214 kPa(-1) in the range of 10-26 kPa). On the other hand, for shear stress, micropillar structures exhibit the highest sensitivity. As proof-of-concept applications in healthcare monitoring devices, we show that our e-skins can precisely monitor acoustic waves, breathing, and human artery/carotid pulse pressures. Unveiling the relationship between the microstructure geometry of e-skins and their sensing capability would provide a platform for future development of high-performance microstructured e-skins

Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay

The decay channel $\psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p})$ is studied using a sample of $1.06\times 10^8$ $\psi^\prime$ events collected by the BESIII experiment at BEPCII. A strong enhancement at threshold is observed in the $p\bar{p}$ invariant mass spectrum. The enhancement can be fit with an $S$-wave Breit-Wigner resonance function with a resulting peak mass of $M=1861^{+6}_{-13} {\rm (stat)}^{+7}_{-26} {\rm (syst)} {\rm MeV/}c^2$ and a narrow width that is $\Gamma<38 {\rm MeV/}c^2$ at the 90% confidence level. These results are consistent with published BESII results. These mass and width values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics