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Biology subjects

Fan, W.

Publications and source records attributed to Fan, W..

4 recordsLinked to original sources

Bidirectional Control of Coronary Vascular Resistance by Eicosanoids via a Novel GPCR

Arachidonic acid metabolites epoxyeicosatrienoates (EETs) and hydroxyeicosatetraenoates (HETEs) are important regulators of myocardial blood flow and coronary vascular resistance (CVR), but their mechanisms of action are not fully understood. We identified G protein-coupled receptor 39 (GPR39) as a microvascular smooth muscle cell (mVSMC) receptor antagonistically regulated by two endogenous eicosanoids: 15-HETE, which stimulates GPR39 to increase mVSMC intracellular calcium and augment microvascular CVR, and 14,15-EET, which inhibits these actions. Furthermore, zinc ion acts as an allosteric modulator of GPR39 to potentiate the efficacy of the two ligands. Our findings will have a major impact on understanding the roles of eicosanoids in cardiovascular physiology and disease, and provide an opportunity for the development of novel GPR39-targeting therapies for cardiovascular disease.\n\nOne Sentence SummaryGPR39 is a microvascular smooth muscle cell receptor regulated by two vasoactive eicosanoids with opposing actions.

physiology

AnatomyNet: Deep 3D Squeeze-and-excitation U-Nets for fast and fully automated whole-volume anatomical segmentation

PurposeRadiation therapy (RT) is a common treatment for head and neck (HaN) cancer where therapists are often required to manually delineate boundaries of the organs-at-risks (OARs). The radiation therapy planning is time-consuming as each computed tomography (CT) volumetric data set typically consists of hundreds to thousands of slices and needs to be individually inspected. Automated head and neck anatomical segmentation provides a way to speed up and improve the reproducibility of radiation therapy planning. Previous work on anatomical segmentation is primarily based on atlas registrations, which takes up to hours for one patient and requires sophisticated atlas creation. In this work, we propose the AnatomyNet, an end-to-end and atlas-free three dimensional squeeze-and-excitation U-Net (3D SE U-Net), for fast and fully automated whole-volume HaN anatomical segmentation.\n\nMethodsThere are two main challenges for fully automated HaN OARs segmentation: 1) challenge in segmenting small anatomies (i.e., optic chiasm and optic nerves) occupying only a few slices, and 2) training model with inconsistent data annotations with missing ground truth for some anatomical structures because of different RT planning. We propose the AnatomyNet that has one down-sampling layer with the trade-off between GPU memory and feature representation capacity, and 3D SE residual blocks for effective feature learning to alleviate these challenges. Moreover, we design a hybrid loss function with the Dice loss and the focal loss. The Dice loss is a class level distribution loss that depends less on the number of voxels in the anatomy, and the focal loss is designed to deal with highly unbalanced segmentation. For missing annotations, we propose masked loss and weighted loss for accurate and balanced weights updating in the learning of the AnatomyNet.\n\nResultsWe collect 261 HaN CT images to train the AnatomyNet, and use MICCAI Head and Neck Auto Segmentation Challenge 2015 as the benchmark dataset to evaluate the performance of the AnatomyNet. The objective is to segment nine anatomies: brain stem, chiasm, mandible, optic nerve left, optic nerve right, parotid gland left, parotid gland right, submandibular gland left, and submandibular gland right. Compared to previous state-of-the-art methods for each anatomy from the MICCAI 2015 competition, the AnatomyNet increases Dice similarity coefficient (DSC) by 3.3% on average. The proposed AnatomyNet takes only 0.12 seconds on average to segment a whole-volume HaN CT image of an average dimension of 178 x 302 x 225. All the data and code will be availablea.\n\nConclusion1We propose an end-to-end, fast and fully automated deep convolutional network, AnatomyNet, for accurate and whole-volume HaN anatomical segmentation. The proposed Anato-myNet outperforms previous state-of-the-art methods on the benchmark dataset. Extensive experiments demonstrate the effectiveness and good generalization ability of the components in the AnatomyNet.

bioengineering

UDP-glucose:anthocyanidin 3-O-glucoside-2”-O-glucosyltransferase catalyzes further glycosylation of anthocyanins in purple Ipomoea batatas

Glycosylation contributes to the diversity and stability of anthocyanins in plants. The process is catalyzed by various glucosyltransferases using different anthocyanidin aglycones and glycosyl donors. An anthocyanidin 3-O-glucoside-2\"-O-glucosyltransferase (3GGT) from purple sweetpotato (cv. Ayamurasaki) served for the catalytic conversion of anthocyanidin 3-O-glucoside into anthocyanidin 3-O-sophoroside, which is functionally different from the 3GGT ortholog of Arabidopsis. The phylogenetic analysis indicates regioselectivity of 3GGT using UDP-xylose or UDP-glucose as the glycosyl is divergent between Convolvulaceae and Arabidopsis. Homology-based protein modeling and site-directed mutagenesis of Ib3GGT and At3GGT suggested that the Thr-138 of Ib3GGT is a key amino acid residue for UDP-glucose recognition and plays a major role in sugar donor selectivity. The wild type and ugt79b1 mutants of Arabidopsis plants overexpressing Ib3GGT produced the new component cyanidin 3-O-sophoroside. Moreover, Ib3GGT expression was associated with anthocyanin accumulation in different tissues during Ayamurasaki plant development and was regulated by the transcription factor IbMYB1. The localization assay of Ib3GGT showed that further glycosylation occurs in the cytosol and not endoplasmic reticulum. The present study revealed the function of Ib3GGT in further glycosylation of anthocyanins and its Thr-138 is the key amino acid residue for UDP-glucose recognition.

plant biology

DeepLung: 3D Deep Convolutional Nets for Automated Pulmonary Nodule Detection and Classification

In this work, we present a fully automated lung CT cancer diagnosis system, DeepLung. DeepLung contains two parts, nodule detection and classification. Considering the 3D nature of lung CT data, two 3D networks are designed for the nodule detection and classification respectively. Specifically, a 3D Faster R-CNN is designed for nodule detection with a U-net-like encoder-decoder structure to effectively learn nodule features. For nodule classification, gradient boosting machine (GBM) with 3D dual path network (DPN) features is proposed. The nodule classification subnetwork is validated on a public dataset from LIDC-IDRI, on which it achieves better performance than state-of-the-art approaches, and surpasses the average performance of four experienced doctors. For the DeepLung system, candidate nodules are detected first by the nodule detection subnetwork, and nodule diagnosis is conducted by the classification subnetwork. Extensive experimental results demonstrate the DeepLung is comparable to the experienced doctors both for the nodule-level and patient-level diagnosis on the LIDC-IDRI dataset.

bioinformatics