iGEMDOCK: a graphical environment of enhancing GEMDOCK using pharmacological interactions and post-screening analysis

<p>Abstract</p> <p>Background</p> <p>Pharmacological interactions are useful for understanding ligand binding mechanisms of a therapeutic target. These interactions are often inferred from a set of active compounds that were acquired experimentally. Moreover, most docking programs loosely coupled the stages (binding-site and ligand preparations, virtual screening, and post-screening analysis) of structure-based virtual screening (VS). An integrated VS environment, which provides the friendly interface to seamlessly combine these VS stages and to identify the pharmacological interactions directly from screening compounds, is valuable for drug discovery.</p> <p>Results</p> <p>We developed an easy-to-use graphic environment, <it>i</it>GEMDOCK, integrating VS stages (from preparations to post-screening analysis). For post-screening analysis, <it>i</it>GEMDOCK provides biological insights by deriving the pharmacological interactions from screening compounds without relying on the experimental data of active compounds. The pharmacological interactions represent conserved interacting residues, which often form binding pockets with specific physico-chemical properties, to play the essential functions of a target protein. Our experimental results show that the pharmacological interactions derived by <it>i</it>GEMDOCK are often hot spots involving in the biological functions. In addition, <it>i</it>GEMDOCK provides the visualizations of the protein-compound interaction profiles and the hierarchical clustering dendrogram of the compounds for post-screening analysis.</p> <p>Conclusions</p> <p>We have developed <it>i</it>GEMDOCK to facilitate steps from preparations of target proteins and ligand libraries toward post-screening analysis. <it>i</it>GEMDOCK is especially useful for post-screening analysis and inferring pharmacological interactions from screening compounds. We believe that <it>i</it>GEMDOCK is useful for understanding the ligand binding mechanisms and discovering lead compounds. <it>i</it>GEMDOCK is available at <url>http://gemdock.life.nctu.edu.tw/dock/igemdock.php</url>.</p

Indoor Depth Completion with Boundary Consistency and Self-Attention

Depth estimation features are helpful for 3D recognition. Commodity-grade depth cameras are able to capture depth and color image in real-time. However, glossy, transparent or distant surface cannot be scanned properly by the sensor. As a result, enhancement and restoration from sensing depth is an important task. Depth completion aims at filling the holes that sensors fail to detect, which is still a complex task for machine to learn. Traditional hand-tuned methods have reached their limits, while neural network based methods tend to copy and interpolate the output from surrounding depth values. This leads to blurred boundaries, and structures of the depth map are lost. Consequently, our main work is to design an end-to-end network improving completion depth maps while maintaining edge clarity. We utilize self-attention mechanism, previously used in image inpainting fields, to extract more useful information in each layer of convolution so that the complete depth map is enhanced. In addition, we propose boundary consistency concept to enhance the depth map quality and structure. Experimental results validate the effectiveness of our self-attention and boundary consistency schema, which outperforms previous state-of-the-art depth completion work on Matterport3D dataset. Our code is publicly available at https://github.com/patrickwu2/Depth-CompletionComment: Accepted by ICCVW (RLQ) 201

FAM129B, an antioxidative protein, reduces chemosensitivity by competing with Nrf2 for Keap1 binding.

BackgroundThe transcription factor Nrf2 is a master regulator of antioxidant response. While Nrf2 activation may counter increasing oxidative stress in aging, its activation in cancer can promote cancer progression and metastasis, and confer resistance to chemotherapy and radiotherapy. Thus, Nrf2 has been considered as a key pharmacological target. Unfortunately, there are no specific Nrf2 inhibitors for therapeutic application. Moreover, high Nrf2 activity in many tumors without Keap1 or Nrf2 mutations suggests that alternative mechanisms of Nrf2 regulation exist.MethodsInteraction of FAM129B with Keap1 is demonstrated by immunofluorescence, colocalization, co-immunoprecipitation and mammalian two-hybrid assay. Antioxidative function of FAM129B is analyzed by measuring ROS levels with DCF/flow cytometry, Nrf2 activation using luciferase reporter assay and determination of downstream gene expression by qPCR and wester blotting. Impact of FAM129B on in vivo chemosensitivity is examined in mice bearing breast and colon cancer xenografts. The clinical relevance of FAM129B is assessed by qPCR in breast cancer samples and data mining of publicly available databases.FindingsWe have demonstrated that FAM129B in cancer promotes Nrf2 activity by reducing its ubiquitination through competition with Nrf2 for Keap1 binding via its DLG and ETGE motifs. In addition, FAM129B reduces chemosensitivity by augmenting Nrf2 antioxidative signaling and confers poor prognosis in breast and lung cancer.InterpretationThese findings demonstrate the important role of FAM129B in Nrf2 activation and antioxidative response, and identify FMA129B as a potential therapeutic target. FUND: The Chang Gung Medical Foundation (Taiwan) and the Ministry of Science and Technology (Taiwan)

Black Soybean Shows Protective Function against Carbon Tetrachloride-induced Liver Damage in Sprague-dawely Rats

ABSTRACT Anthocyanins are abounding in the seed coat of black soybean (BS) (Glycine max (L.) Merrill), which contribute to anti-oxidative and anti-antiinflammatory activities. It leaded us to investigate the protective function of BS against a strong oxidant carbon tetrachloride (CCl 4 ) induced liver damage in rats. BS was baked at 130°C for 5 min and then was submerged in 100°C hot water for 20 min to produce an anthocyanin enriched tea/decoction (BST). Protective function of BST against CCl 4 -induced liver damage in Sprague-Dawely rats was investigated with six experimental groups: control, high BST (1 g BS/kg bw), CCl 4 (0.5 ml 20% CCl 4 ), CCl 4 + silymarin (0.2 g/kg bw), CCl 4 + low BST (0.1 g BS/kg bw) and CCl 4 + high BST (1 g BS/kg bw). BST enhanced GSH and GSSH contents, as well as antioxidant enzymes activities (superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities) in the liver tissue of normal rats. BST also attenuated the elevation of serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) levels in CCl 4 treated rats. Liver histopathology revealed that BST reduced fatty liver and liver fibrosis caused by CCl 4 . It was suggested that anthocyanins in the seed coat of black soybean contributed to such hepatoprotective effect

Polysaccharides obtained from mycelia of Cordyceps militaris attenuated doxorubicin-induced cytotoxic effects in chemotherapy

Objectives: Fungus Cordyceps militaris has been used as a herbal tonic in traditional Chinese medicine, which could be surface liquid-cultured for mycelia production. To evaluate the potential of polysaccharides obtained from mycelia of Cordyceps militaris (PS-MCM) for attenuation of side-effects of chemotherapy.Methods: Doxorubicin was used to induce cytotoxicity in THP-1 monocytes and EL-4 T cells, and the effects of PS-MCM on cell viability and cytokine production were detected on doxorubicin-treated THP-1 and EL-4 cells.Results: PS-MCM reduced doxorubicin-induced cell death and promoted cell proliferation in THP-1 and EL-4 cells. Moreover, PS-MCM elevated the level of cytokines associated with immune-modulation of THP-1 and EL-4 cells.Conclusion: These findings indicate that PS-MCM has potential for development as a functional food to counteract side effects of chemotherapy.Keywords: Cordyceps militaris, traditional Chinese medicine, doxorubicin, chemotherapy, immunotherapy

Multi-Segment Foam Flow Field in Ambient Pressure Polymer Exchange Membrane Fuel Cell

In order to produce low-cost flow field plates for polymer electrolyte membrane fuel cells, we used nickel foam in this study rather than conventional flow field. Nickel foam has high electron conductivity, thermal conductivity, and mechanical strength. Electrochemical impedance spectrum analysis is carried out to evidence the use on flow field plates of nickel foam. From the impedance fitting results, the nickel foam cases showed the lower contact resistance than the serpentine. However, such plates have poor performance at low temperatures and ambient pressure. In order to overcome this, a multi-segment foam flow field is designed in this study. This increased the performance of the polarization curve by 70% from 162 to 275.5 mw cm-2 than the original nickel foam design. Also, the mass transfer resistance was reduced, and the Warburg impedance value of the operation voltage decreased by 0.4 V. The numerical analysis results demonstrate that increased segment numbers can increase the performance of the multi-segment foam flow field