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

Comparison of lower extremity atherosclerosis in diabetic and non-diabetic patients using multidetector computed tomography

BACKGROUND: Lower extremity atherosclerosis (LEA) is among the most serious diabetic complications and leads to non-traumatic amputations. The recently developed dual-source CT (DSCT) and 320- multidetector computed tomography (MDCT) may help to detect plaques more precisely. The aim of our study was to evaluate the differences in LEA between diabetic and non-diabetic patients using MDCT angiography. METHODS: DSCT and 320-MDCT angiographies of the lower extremities were performed in 161 patients (60 diabetic and 101 non-diabetic). The plaque type, distribution, shape and obstructive natures were compared. RESULTS: Compared with non-diabetic patients, diabetic patients had higher peripheral neuropathy, history of cerebrovasuclar infarction and hypertension rates. A total of 2898 vascular segments were included in the analysis. Plaque and stenosis were detected in 681 segments in 60 diabetic patients (63.1%) and 854 segments in 101 non-diabetic patients (46.9%; p <0.05). Regarding these plaques, diabetic patients had a higher incidence of mixed plaques (34.2% vs. 27.1% for non-diabetic patients). An increased moderate stenosis rate and decreased occlusion rate were observed in diabetic patients relative to non-diabetic patients (35.8% vs. 28.3%; and 6.6% vs. 11.4%; respectively). In diabetic patients, 362 (53.2%) plaques were detected in the distal lower leg segments, whereas in non-diabetic patients, 551 (64.5%) plaques were found in the proximal upper leg segments. The type IV plaque shape, in which the full lumen was involved, was detected more frequently in diabetic patients than in non-diabetic patients (13.1% vs. 8.2%). CONCLUSION: Diabetes is associated with a higher incidence of plaque, increased incidence of mixed plaques, moderate stenosis and localisation primarily in the distal lower leg segments. The advanced and non-invasive MDCT could be used for routine preoperative evaluations of LEA

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

Different cerebral plasticity of intrinsic and extrinsic hand muscles after peripheral neurotization in a patient with brachial plexus injury: A TMS and fMRI study

AbstractContralateral C7 (CC7) neurotization has been an important approach for brachial plexus injury (BPI). Patients can achieve relatively good grasping function driven by the proximal extrinsic hand muscle (flexor digitorum, FD) after CC7 neurotization, whereas the thumb opposition function driven by the distal intrinsic muscle (abductor pollicis brevis, APB) is poor. The present study aimed to investigate the brain reorganization patterns of the recovery processes of intrinsic and extrinsic hand functions after repairing the median nerve by CC7 neurotization. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) were used to evaluate the cerebral plasticity in one BPI patient after CC7 neurotization. After the CC7 neurotization, the patient showed improvements in the paralyzed hand. Combination of TMS and fMRI investigations demonstrated different cortical reshaping patterns of APB and FD. It was also found that the activated cortical areas of FD were located in bilateral motor cortices, but the area of APB was only located in ipsilateral motor cortex. The cerebral plasticity procedure appeared to be different in the gross and fine motor function recovery processes. It provided a new perspective into the cerebral plasticity induced by CC7 neurotization

Transport evidence for the surface state and spin-phonon interaction in FeTe0.5_{0.5}Se0.5_{0.5}

The iron chalcogenides have been proved to be intrinsic topological superconductors to implement quantum computation because of their unique electronic structures. The topologically nontrivial surface states of FeTe$_{0.5}$Se$_{0.5}$ have been predicted by several calculations and then confirmed by high-resolution photoemission and scanning tunneling experiments. However, so far, the shreds of the electrical transport evidence for topological surface states are still in absence. By carrying out electrical transport experiments, we observe a topological transition with a nonlinear Hall conductivity and simultaneous linear magnetoresistance near the superconducting transition temperature. Furthermore, we observe a sign reversal of the Hall coefficient accompanied by a concurrently softening of the ${A}_{1g}$ phonon mode at about 40 K, indicating a nematic transition. The synchronized phonon softening with nematicity manifests an enhanced fluctuation state through spin-phonon interaction. Our results solidly corroborate the topological surface states of FeTe$_{0.5}$Se$_{0.5}$ and provide an understanding of the mechanism of the superconductivity in iron chalcogenides.Comment: 10 pages, 8 figure

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

WebBrain: Learning to Generate Factually Correct Articles for Queries by Grounding on Large Web Corpus

In this paper, we introduce a new NLP task -- generating short factual articles with references for queries by mining supporting evidence from the Web. In this task, called WebBrain, the ultimate goal is to generate a fluent, informative, and factually-correct short article (e.g., a Wikipedia article) for a factual query unseen in Wikipedia. To enable experiments on WebBrain, we construct a large-scale dataset WebBrain-Raw by extracting English Wikipedia articles and their crawlable Wikipedia references. WebBrain-Raw is ten times larger than the previous biggest peer dataset, which can greatly benefit the research community. From WebBrain-Raw, we construct two task-specific datasets: WebBrain-R and WebBrain-G, which are used to train in-domain retriever and generator, respectively. Besides, we empirically analyze the performances of the current state-of-the-art NLP techniques on WebBrain and introduce a new framework ReGen, which enhances the generation factualness by improved evidence retrieval and task-specific pre-training for generation. Experiment results show that ReGen outperforms all baselines in both automatic and human evaluations.Comment: Codes in https://github.com/qhjqhj00/WebBrai

Snailase Preparation of Ginsenoside M1 from Protopanaxadiol-Type Ginsenoside and Their Protective Effects Against CCl4-Induced Chronic Hepatotoxicity in Mice

To investigate the protective effects of protopanaxadiol-type ginsenoside (PDG) and its metabolite ginsenoside M1 (G-M1) on carbon tetrachloride (CCl4)-induced chronic liver injury in ICR mice, we carried out conversion of protopanaxadiol-type ginsenosides to ginsenoside M1 using snailase. The optimum time for the conversion was 24 h at a constant pH of 4.5 and an optimum temperature of 50 °C. The transformation products were identified by high-performance liquid chromatography and electrospray ion-mass spectrometry. Subsequently, most of PDG was decomposed and converted into G-M1 by 24 h post-reaction. During the study on hepatoprotective in a mice model of chronic liver injury, PDG or G-M1 supplement significantly ameliorated the CCl4-induced liver lesions, lowered the serum levels of select hepatic enzyme markers (alanine aminotransferase, ALT, and aspartate aminotransferase, AST) and malondialdehyde and increased the activity of superoxide dismutase in liver. Histopathology of the liver tissues showed that PDG and G-M1 attenuated the hepatocellular necrosis and led to reduction of inflammatory cell infiltration. Therefore, the results of this study show that PDG and G-M1 can be proposed to protect the liver against CCl4-induced oxidative injury in mice, and the hepatoprotective effect might be attributed to amelioration of oxidative stress

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&lt;0.05) and no significant difference existed between them (P&gt;0.05). The serum levels of FSH did not change  significantly after the treatment (P&gt;0.05) and no significant difference existed between them (P&gt;0.05). The  serum levels of E2 significantly increased in both of the two groups (P&lt;0.05) and it increased more in the comparison group (P&lt;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