Physiological functions of a methuselah-like G protein coupled receptor in Lymantria dispar Linnaeus

Insect G protein coupled receptors (GPCRs) have been identified as a highly attractive target for new generation insecticides discovery due to their critical physiological functions. However, few insect GPCRs have been functionally characterized. Here, we cloned the full length of a methuselah-like GPCR gene (Ldmthl1) from the Asian gypsy moth, Lymantria dispar. We then characterized the secondary and tertiary structures of Ldmthl1. We also predicted the global structure of this insect GPCR protein which is composed of three major domains. RNA interference of Ldmthl1 resulted in a reduction of gypsy moths\u27 resistance to deltamethrin and suppressed expression of downstream stress-associated genes, such as P450s, glutathione S transferases, and heat shock proteins. The function of Ldmthl1 was further investigated using transgenic lines of Drosophila melanogaster. Drosophila with overexpression of Ldmthl1 showed significantly longer lifespan than control flies. Taken together, our studies revealed that the physiological functions of Ldmthl1 in L. dispar are associated with longevity and resistance to insecticide stresses. Potentially, Ldmthl1 can be used as a target for new insecticide discovery in order to manage this notorious forest pest

GsAPK, an ABA-Activated and Calcium-Independent SnRK2-Type Kinase from G. soja, Mediates the Regulation of Plant Tolerance to Salinity and ABA Stress

Plant Snf1 (sucrose non-fermenting-1) related protein kinase (SnRK), a subfamily of serine/threonine kinases, has been implicated as a crucial upstream regulator of ABA and osmotic signaling as in many other signaling cascades. In this paper, we have isolated a novel plant specific ABA activated calcium independent protein kinase (GsAPK) from a highly salt tolerant plant, Glycine soja (50109), which is a member of the SnRK2 family. Subcellular localization studies using GFP fusion protein indicated that GsAPK is localized in the plasma membrane. We found that autophosphorylation and Myelin Basis Protein phosphorylation activity of GsAPK is only activated by ABA and the kinase activity also was observed when calcium was replaced by EGTA, suggesting its independence of calcium in enzyme activity. We also found that cold, salinity, drought, and ABA stress alter GsAPK gene transcripts and heterogonous overexpression of GsAPK in Arabidopsis alters plant tolerance to high salinity and ABA stress. In summary, we demonstrated that GsAPK is a Glycine soja ABA activated calcium independent SnRK-type kinase presumably involved in ABA mediated stress signal transduction

Microscopic magnetic dipole radiation in neutron stars

There is ${}^3P_2$ neutron superfluid region in NS (neutron star) interior. For a rotating NS, the ${}^3P_2$ superfluid region is like a system of rotating magnetic dipoles. It will give out electromagnetic radiation, which may provides a new heating mechanism of NSs. This heating mechanism plus some cooling agent may give sound explanation to NS glitches.Comment: To be published by ChJA

Penetration and pharmacokinetics of ferulic acid after dermal administration

Purpose: To study the in vitro penetration and in vivo pharmacokinetics of ferulic acid (FA), and the correlation between them after dermal administration. Methods: Franz diffusion cell was used to study in vitro penetration of FA. The concentration of FA in the Franz receiver solution was assessed by high performance liquid chromatography (HPLC). Prior to in vivo pharmacokinetics experiments, probe recovery was validated with respect to influencing factors such as flow rate, FA concentration, within-day stability and reproducibility of the probes. In in vivo pharmacokinetic experiment, six male CD-1 hairless mice were used. The micro-dialysis (MD) probe was implanted in the dermis of the rat skin, and dialysates from probe outlet were quantified directly by HPLC. In in vivo studies, deconvolution methods were used to determine the relationship between in vitro and in vivo data, and the correlation coefficient of linear equations. Results: There was significant effect of pH (5 ~ 8) on the penetration of FA. Increase in pH caused commensurate decrease in permeability. The Cmax of FA was 300.74 ± 31.86 ng/mL while Tmax was 138.00 ± 22.80 min after dermal administration of 1 mg/mL FA dissolved in phosphate buffered saline (PBS). The correlation coefficient (r) between in vitro and in vivo data was 0.9905. Conclusion: Both in vivo and in vitro experiments demonstrate that FA permeates the stratum corneum of skin rapidly. The unionized form of FA shows better penetration than the ionic form. In addition, results from correlation analysis indicate that the in vitro penetration characteristics of FA can be applied to predict its in vivo pharmacokinetics

Intermolecular Failure of L-type Ca(2+) Channel and Ryanodine Receptor Signaling in Hypertrophy

Pressure overload–induced hypertrophy is a key step leading to heart failure. The Ca(2+)-induced Ca(2+) release (CICR) process that governs cardiac contractility is defective in hypertrophy/heart failure, but the molecular mechanisms remain elusive. To examine the intermolecular aspects of CICR during hypertrophy, we utilized loose-patch confocal imaging to visualize the signaling between a single L-type Ca(2+) channel (LCC) and ryanodine receptors (RyRs) in aortic stenosis rat models of compensated (CHT) and decompensated (DHT) hypertrophy. We found that the LCC-RyR intermolecular coupling showed a 49% prolongation in coupling latency, a 47% decrease in chance of hit, and a 72% increase in chance of miss in DHT, demonstrating a state of “intermolecular failure.” Unexpectedly, these modifications also occurred robustly in CHT due at least partially to decreased expression of junctophilin, indicating that intermolecular failure occurs prior to cellular manifestations. As a result, cell-wide Ca(2+) release, visualized as “Ca(2+) spikes,” became desynchronized, which contrasted sharply with unaltered spike integrals and whole-cell Ca(2+) transients in CHT. These data suggested that, within a certain limit, termed the “stability margin,” mild intermolecular failure does not damage the cellular integrity of excitation-contraction coupling. Only when the modification steps beyond the stability margin does global failure occur. The discovery of “hidden” intermolecular failure in CHT has important clinical implications

Prevalence, incidence and mortality of hypertrophic cardiomyopathy based on a population cohort of 21.9 million in China

There are limited studies on the prevalence and incidence of clinically diagnosed hypertrophic myocardiopathy (HCM) and its mortality in the Chinese population, and the projected population burden of HCM over the next decades. We collected data on HCM and its mortality from the Beijing Municipal Health Commission Information Center (BMHCIC) database and estimated the prevalence and incidence based on the whole Beijing population. Calculation of population trends was performed using annual percentage change (APC) and average annual percentage change (AAPC). Finally, future HCM incidence was built by modelling projection of HCM to the next decades using Poisson regression analysis and Gray Model 1,1(GM [1,1]). The prevalence of HCM was 0.0069% (95%CI, 0.0065–0.0072%; N = 1343) in 2010, rising to 0.076% (95% CI, 0.074–0.077%; N = 16,616) in 2019, and the incidence of HCM was 6.85 per 100 000 person-year in 2010, rising to 11.76 per 100 000 person-year in 2019. Males had higher prevalence and incidence of HCM than females. The APPC for the rising incidence of HCM was 5.8% and the expected numbers will double increase in 2029 by assuming the same increase trend as the last decades. HCM had increased annual incidence of HF (APPC: 8.4, 4.4–12.6, p  0.05) during the studied period. Males had lower mortality (2.70% vs. 4.20%, p < 0.001) than females. The calculated HCM prevalence was much lower compared to prior screening studies from 2004, although the predicted HCM incidence would double over the next decades. HCM was associated with a stable risk of mortality during the studied period