Novel GATA5 loss-of-function mutations underlie familial atrial fibrillation

OBJECTIVE: This study aimed to identify novel GATA5 mutations that underlie familial atrial fibrillation. METHODS: A total of 110 unrelated patients with familial atrial fibrillation and 200 unrelated, ethnically matched healthy controls were recruited. The entire coding region of the GATA5 gene was sequenced in 110 atrial fibrillation probands. The available relatives of the mutation carriers and 200 controls were subsequently genotyped for the identified mutations. The functional effect of the mutated GATA5 was characterized using a luciferase reporter assay system. RESULTS: Two novel heterozygous GATA5 mutations (p.Y138F and p.C210G) were identified in two of the 110 unrelated atrial fibrillation families. These missense mutations cosegregated with AF in the families and were absent in the 400 control chromosomes. A cross-species alignment of GATA5 protein sequence showed that the altered amino acids were completely conserved evolutionarily. A functional analysis revealed that the mutant GATA5 proteins were associated with significantly decreased transcriptional activation when compared with their wild-type counterpart. CONCLUSION: The findings expand the spectrum of GATA5 mutations linked to AF and provide novel insights into the molecular mechanism involved in the pathogenesis of atrial fibrillation, suggesting potential implications for the early prophylaxis and personalized treatment of this common arrhythmia

Simulation Study of Bionic Jetting Direction Influence on Drag Reduction Effect

By imitating the jetting flow feature of shark gills，a bionic jetting model is established by arranging round outlets on a flat plate. The drag reduction effect under different jetting directions are explored using numerical simulation method when the main flow field velocity was 20m/s and the reasons of drag reduction are analyzed simultaneously. The results of simulation showed that：different jetting directions affecte the wall shear stress and static pressure of flow field which result in the changing of viscous resistance and pressure drag; the bionic jetting has the best drag reduction effect when jetting direction angle is 30 degrees; under different jetting direction conditions, the main reason of drag reduction is the substantially decreased pressure drag. Key words：bionics; drag reduction; jetting flow; numerical simulation; viscous resistance; pressure dra

Molecular identification and food source inference of constructive plants, native to the Ophiocordyceps sinensis habitat

Ophiocordyceps sinensis is a precious and effectual Traditional Chinese Medicine, native to Tibetan Plateau. Its development originated from parasitization of Hirsutella sinensis to Hepialus larvae, which was deemed to be of great importance including feeding food habit. Hereby in the present, study on food resource plants and their molecular identification technique were performed by some methods such as vegetation investigation, morphological taxonomy, sequence alignment, phylogenetic inference, primer design and correlation analysis and so on. In consequence, molecular identification system of constructive plants native to the O. sinensis habitat was established, and then feeding food habit of Hepialus pui larvae and its correlation with genesis mechanism of O. sinensis were preliminarily analyzed and discussed. It is very significant for phylogenetic systematicbotany research of plateau plants on a relative large scale, and it is the first time to study feeding food habit of Hepialus larvae and its related infected process on the molecular level.Keywords: Phylogenetic inference, molecular identification, constructive plant, Ophiocordyceps sinensis, Hepialus pu

A CRY-BIC negative-feedback circuitry regulating blue light sensitivity of Arabidopsis.

Cryptochromes are blue light receptors that regulate various light responses in plants. Arabidopsis cryptochrome 1 (CRY1) and cryptochrome 2 (CRY2) mediate blue light inhibition of hypocotyl elongation and long-day (LD) promotion of floral initiation. It has been reported recently that two negative regulators of Arabidopsis cryptochromes, Blue light Inhibitors of Cryptochromes 1 and 2 (BIC1 and BIC2), inhibit cryptochrome function by blocking blue light-dependent cryptochrome dimerization. However, it remained unclear how cryptochromes regulate the BIC gene activity. Here we show that cryptochromes mediate light activation of transcription of the BIC genes, by suppressing the activity of CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1), resulting in activation of the transcription activator ELONGATED HYPOCOTYL 5 (HY5) that is associated with chromatins of the BIC promoters. These results demonstrate a CRY-BIC negative-feedback circuitry that regulates the activity of each other. Surprisingly, phytochromes also mediate light activation of BIC transcription, suggesting a novel photoreceptor co-action mechanism to sustain blue light sensitivity of plants under the broad spectra of solar radiation in nature

Experimental and numerical simulation studies of the squeezing dynamics of the UBVT system with a hole-plug device

In this paper, a method is proposed to secure an autonomous underwater blasting vibration test (UBVT) system with plugs to deep-water rock, and its specific configuration concept and plugging principle are illustrated. Using the principle of statics, a mathematical model is established for the squeezing force in the process of pressing the hole-plug device (HPD) into holes in rocks. The tension-compression test is conducted on the plugs in round granite holes to obtain the axial pressure-displacement curves of the pressing process with the HPD spring parameter K, friction coefficient μ between the HPD and the rock-wall, and the dynamic contact friction attributes between the metallic HPD and the rock-wall of hole in granite. The axial pressure with such parameters as K, μ, and the squeezing velocity v, among others, and the four steps of the pressing process are numerically simulated. The relations of the characteristic squeezing force with K, μ, and v, as well as the mechanisms of these parameters that influence HPD usage and the sensitivity coefficient, are revealed. The findings of the present study provide references for setting the HPD configuration parameters and for formulating plug-specific construction methods

Effects of vertical advection on multimessenger signatures of black hole neutrino-dominated accretion flows in compact binary coalescences

In the coalescence events of binary neutron star (NS) or a black hole (BH) and an NS, a BH hyperaccretion disk might be eventually formed. At very high mass accretion rates, MeV neutrinos will be emitted from this disk, which is called a neutrino-dominated accretion flow (NDAF). Neutrino annihilation in the space out of the disk is energetic enough to launch ultrarelativistic jets to power gamma-ray bursts. Moreover, vertical advection might exist in NDAFs, which can generate the magnetic buoyancy bubbles to release gamma-ray photons. In this paper, we visit the effects of the vertical advection in NDAFs on the disk structure and gamma-ray and neutrino luminosities for different accretion rates. Then we study the anisotropic emission of kilonovae and the following gravitational waves (GWs) driven by the gamma-ray photons and neutrinos from NDAFs. Comparing NDAFs without vertical advection, the neutrino luminosity and GW strains slightly decrease for the case with vertical advection, and the kilonovae will be brightened by the injected gamma-ray photons. The future joint multimessenger observations might distinguish whether the vertical advection exists in NDAFs or not after compact binary coalescences.Comment: 14 pages, 7 figures, accepted for publication in Ap

Zhi-Bai-Di-Huang-Wan, a classic Chinese medicinal formula in relieving menopausal symptoms: A multi-centre and controlled trial from UK and China

Background: To explore the effects of Zhi-Bai-Di-Huang-Wan (ZBDHW), a classic formula of Chinese  medicinal herbs in relieving menopausal symptoms in British and Chinese women.Methods and Materials: Between May 2011 and May 2013, 224 Chinese and British women were  divided into a ZBDHW group with 115 cases and a control group with 109 cases. The clinical menopausal  symptoms were assessed by the modified Kupperman Index Scale. The serum levels of follicle stimulating hormone (FSH) and estradiol (E2) were respectively detected before and after the treatment. Results: After 12 weeks of treatment, both groups’ Kupperman index scores markedly decreased  (P<0.05) and no significant difference existed between them (P>0.05). The serum levels of FSH did not change  significantly after the treatment (P>0.05) and no significant difference existed between them (P>0.05). The  serum levels of E2 significantly increased in both of the two groups (P<0.05) and it increased more in the comparison group (P<0.05). No side-effect of the treatment was reported in both of the two groups during the  period of the treatment.Conclusion: The classic Chinese medicinal formula, ZBDHW, showed promise in relieving menopausal  symptoms.Key words: Chinese medicinal herb; Zhi-Bai-Di-Huang-Wan (ZBDHW); menopausal symptom

Discovery, Semisynthesis, Antiparasitic and Cytotoxic Evaluation of 14-Membered Resorcylic Acid Lactones and Their Derivatives

Ten antifouling 14-membered resorcylic acid lactones 1–10 were isolated previously with low or trace natural abundance from the zoanthid-derived Cochliobolus lunatus fungus. Further optimization of fermentation conditions led to the isolation of two major natural compounds 7 and 8 with multi-gram quantities. By one or two steps, we semisynthesized the six trace natural compounds 1–6 and a series of derivatives 11–27 of compounds 7 and 8 with high yields (65–95%). Compounds 11–13 showed strong antiplasmodial activity against Plasmodium falciparum with IC50 values of 1.84, 8.36, and 6.95μM, respectively. Very importantly, 11 and 12 were non-toxic with very safety and high therapeutic indices (CC50/IC50>180), and thus representing potential promising leads for antiplasmodial drug discovery. Furthermore, 11 was the only compound showed obvious antileishmanial activity against Leishmania donovani with an IC50 value of 9.22μM. Compounds 11 and 12 showed the values of IC50 at 11.9 and 17.2μM against neglected Chagas’ disease causing Trypanosoma cruzi, respectivelyTen antifouling 14-membered resorcylic acid lactones 1–10 were isolated previously with low or trace natural abundance from the zoanthid-derived Cochliobolus lunatus fungus. Further optimization of fermentation conditions led to the isolation of two major natural compounds 7 and 8 with multi-gram quantities. By one or two steps, we semisynthesized the six trace natural compounds 1–6 and a series of derivatives 11–27 of compounds 7 and 8 with high yields (65–95%). Compounds 11–13 showed strong antiplasmodial activity against Plasmodium falciparum with IC50 values of 1.84, 8.36, and 6.95μM, respectively. Very importantly, 11 and 12 were non-toxic with very safety and high therapeutic indices (CC50/IC50>180), and thus representing potential promising leads for antiplasmodial drug discovery. Furthermore, 11 was the only compound showed obvious antileishmanial activity against Leishmania donovani with an IC50 value of 9.22μM. Compounds 11 and 12 showed the values of IC50 at 11.9 and 17.2μM against neglected Chagas’ disease causing Trypanosoma cruzi, respectivel