Protein subcellular localization prediction of eukaryotes using a knowledge-based approach

<p>Abstract</p> <p>Background</p> <p>The study of protein subcellular localization (PSL) is important for elucidating protein functions involved in various cellular processes. However, determining the localization sites of a protein through wet-lab experiments can be time-consuming and labor-intensive. Thus, computational approaches become highly desirable. Most of the PSL prediction systems are established for single-localized proteins. However, a significant number of eukaryotic proteins are known to be localized into multiple subcellular organelles. Many studies have shown that proteins may simultaneously locate or move between different cellular compartments and be involved in different biological processes with different roles.</p> <p>Results</p> <p>In this study, we propose a knowledge based method, called KnowPred_site, to predict the localization site(s) of both single-localized and multi-localized proteins. Based on the local similarity, we can identify the "related sequences" for prediction. We construct a knowledge base to record the possible sequence variations for protein sequences. When predicting the localization annotation of a query protein, we search against the knowledge base and used a scoring mechanism to determine the predicted sites. We downloaded the dataset from ngLOC, which consisted of ten distinct subcellular organelles from 1923 species, and performed ten-fold cross validation experiments to evaluate KnowPred_site's performance. The experiment results show that KnowPred_siteachieves higher prediction accuracy than ngLOC and Blast-hit method. For single-localized proteins, the overall accuracy of KnowPred_siteis 91.7%. For multi-localized proteins, the overall accuracy of KnowPred_siteis 72.1%, which is significantly higher than that of ngLOC by 12.4%. Notably, half of the proteins in the dataset that cannot find any Blast hit sequence above a specified threshold can still be correctly predicted by KnowPred_site.</p> <p>Conclusion</p> <p>KnowPred_sitedemonstrates the power of identifying related sequences in the knowledge base. The experiment results show that even though the sequence similarity is low, the local similarity is effective for prediction. Experiment results show that KnowPred_siteis a highly accurate prediction method for both single- and multi-localized proteins. It is worth-mentioning the prediction process of KnowPred_siteis transparent and biologically interpretable and it shows a set of template sequences to generate the prediction result. The KnowPred_siteprediction server is available at <url>http://bio-cluster.iis.sinica.edu.tw/kbloc/</url>.</p

Hypolipidemic Effects of Three Purgative Decoctions

In traditional Chinese medicine (TCM), purgation is indicated when a person suffers an illness due to the accumulation of evil internal heat. Obese individuals with a large belly, red face, thick and yellow tongue fur, constipation, and avoidance of heat are thought accumulates of evil internal heat, and they are also treated with purgatives such as Ta-Cheng-Chi-Tang (TCCT), Xiao-Chen-Chi-Tang (XCCT), and Tiao-Wei-Chen-Chi-Tang (TWCCT) by TCM doctors. In previous studies, our group found that TCCT has potent anti-inflammatory activity, and that XCCT is an effective antioxidant. Since rhubarb is the principle herb in these three prescriptions, we will first present a thorough review of the literature on the demonstrated effect (or lack of effect) of rhubarb and rhubarb-containing polyherbal preparations on lipid and weight control. We will then continue our research with an investigation of the anti-obesity and lipid-lowering effect of TCCT, XCCT, TWCCT, and rhubarb extracts using two animal models. TWCCT lowered the serum triglyceride concentration as much as fenofibrate in Triton WR-1339-treated mice. Daily supplementation with XCCT and TWCCT significantly attenuated the high-fat-diet-induced hypercholesterolemia in rats. In addition, TWCCT also significantly lowered the high-fat-diet-induced hypertriglycemia. Although feeding high-fat diet rats with these extracts did not cause loose stools or diarrhea or other deleterious effects on renal or hepatic function. None of these extracts lowered the body weight of rats fed on high-fat diet. In conclusion, the results suggest that XCCT and TWCCT might exert beneficial effects in the treatment of hyperlipidemia

Enhancement of external wall decoration material for the building in safety inspection method

As buildings wear out, external wall tiles or attachments will usually fall off, sometimes causing human injuries. At present, the method employed for middle-high rise buildings is mainly the method of visual inspection. The inspection results in using this method are affected by the factors of subjectivity, safety and cost. This study aims to provide a lowercost and more efficient evaluation method for inspecting the status of buildings’ external walls. This proposed method implements Forward Looking Infrared (FLIR) technology and high-resolution photographic equipment on Unmanned Aerial Vehicle (UAV) which can improve the image recording of the detection process, as well as the overall visual detection technology, and solve the existing visual detection problem of inspectors. Also, the images detected by visual inspection and UAV high-resolution video are used to develop a suitable visual evaluation process and test table for external walls. Through the test results of several cases, the deterioration status and needs for maintenance are taken into account according to the degree of performance indicators. The findings of the study is that the proposed mechanism is more efficient and lower cost for the detection of external walls or ancillary structures’ abnormal status, which is easy to use in practice

Discovery of New Eunicellins from an Indonesian Octocoral Cladiella sp.

Two new 11-hydroxyeunicellin diterpenoids, cladieunicellin F (1) and (–)-solenopodin C (2), were isolated from an Indonesian octocoral Cladiella sp. The structures of eunicellins 1 and 2 were established by spectroscopic methods, and eunicellin 2 was found to be an enantiomer of the known eunicellin solenopodin C (3). Eunicellin 2 displayed inhibitory effects on the generation of superoxide anion and the release of elastase by human neutrophils. The previously reported structures of two eunicellin-based compounds, cladielloides A and B, are corrected in this study

Excavatoids O and P, New 12-Hydroxybriaranes from the Octocoral Briareum excavatum

Two new 12-hydroxybriarane diterpenoids, designated as excavatoids O (1) and P (2), were isolated from the octocoral Briareum excavatum. The structures of briaranes 1 and 2 were established on the basis of extensive spectral data analysis. Excavatoid P (2) is the first metabolite which possesses a 6β -chlorine atom in briarane analogues

REG3A overexpression functions as a negative predictive and prognostic biomarker in rectal cancer patients receiving CCRT

Background. Concurrent chemoradiotherapy (CCRT) is suggested before resection surgery in the control of rectal cancer. Unfortunately, treatment outcomes are widely variable and highly patientspecific. Notably, rectal cancer patients with distant metastasis generally have a much lower survival rate. Accordingly, a better understanding of the genetic background of patient cohorts can aid in predicting CCRT efficacy and clinical outcomes for rectal cancer before distant metastasis. Methods. A published transcriptome dataset (GSE35452) (n=46) was utilized to distinguish prospective genes concerning the response to CCRT. We recruited 172 rectal cancer patients, and the samples were collected during surgical resection after CCRT. Immunohistochemical (IHC) staining was performed to evaluate the expression level of regenerating family member 3 alpha (REG3A). Pearson's chi-squared test appraised the relevance of REG3A protein expression to clinicopathological parameters. The Kaplan-Meier method was utilized to generate survival curves, and the log-rank test was performed to compare the survival distributions between two given groups. Results. Employing a transcriptome dataset (GSE35452) and focusing on the inflammatory response (GO: 0006954), we recognized that REG3A is the most significantly upregulated gene among CCRT nonresponders (log2 ratio=1.2472, p=0.0079). Following IHC validation, high immunoexpression of REG3A was considerably linked to advanced post-CCRT tumor status (p<0.001), post-CCRT lymph node metastasis (p=0.042), vascular invasion (p=0.028), and low-grade tumor regression (p=0.009). In the multivariate analysis, high immunoexpression of REG3A was independently correlated with poor disease-specific survival (DSS) (p=0.004) and metastasis-free survival (MeFS) (p=0.045). The results of the bioinformatic analysis also supported the idea that REG3A overexpression is implicated in rectal carcinogenesis. Conclusion. In the current study, we demonstrated that REG3A overexpression is correlated with poor CCRT effectiveness and inferior patient survival in rectal cancer. The predictive and prognostic utility of REG3A expression may direct patient stratification and decisionmaking more accurately for those patients

Insights on Distinct Left Atrial Remodeling Between Atrial Fibrillation and Heart Failure With Preserved Ejection Fraction

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) commonly coexist with overlapping pathophysiology like left atrial (LA) remodeling, which might differ given different underlying mechanisms. OBJECTIVES: We sought to investigate the different patterns of LA wall remodeling in AF vs. HFpEF. METHODS: We compared LA wall characteristics including wall volume (LAWV), wall thickness (LAWT), and wall thickness heterogeneity (LAWT[SD]) and LA structure, function among the controls (without AF or HFpEF, n = 115), HFpEF alone (n = 59), AF alone (n = 37), and HFpEF+AF (n = 38) groups using multi-detector computed tomography and echocardiography. RESULTS: LA wall remodeling was most predominant and peak atrial longitudinal strain (PALS) was worst in HFpEF+AF patients as compared to the rest. Despite lower E/e' (9.8 ± 3.8 vs. 13.4 ± 6.4) yet comparable LA volume, LAWT and PALS in AF alone vs. HFpEF alone, LAWV [12.6 (11.6–15.3) vs. 12.0 (10.2–13.7); p = 0.01] and LAWT(SD) [0.68 (0.61–0.71) vs. 0.60 (0.56–0.65); p < 0.001] were significantly greater in AF alone vs. HFpEF alone even after multi-variate adjustment and propensity matching. After excluding the HFpEF+AF group, both LAWV and LAWT [SD] provided incremental values when added to PALS or LAVi (all p for net reclassification improvement <0.05) in discriminating AF alone, with LAWT[SD] yielding the largest C-statistic (0.78, 95% CI: 0.70–0.86) among all LA wall indices. CONCLUSIONS: Despite a similar extent of LA enlargement and dysfunction in HFpEF vs. AF alone, larger LAWV and LAWT [SD] can distinguish AF from HFpEF alone, suggesting the distinct underlying pathophysiological mechanism of LA remodeling in AF vs. HFpEF

Insights on Distinct Left Atrial Remodeling Between Atrial Fibrillation and Heart Failure With Preserved Ejection Fraction

Background: Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) commonly coexist with overlapping pathophysiology like left atrial (LA) remodeling, which might differ given different underlying mechanisms. Objectives: We sought to investigate the different patterns of LA wall remodeling in AF vs. HFpEF. Methods: We compared LA wall characteristics including wall volume (LAWV), wall thickness (LAWT), and wall thickness heterogeneity (LAWT[SD]) and LA structure, function among the controls (without AF or HFpEF, n = 115), HFpEF alone (n = 59), AF alone (n = 37), and HFpEF+AF (n = 38) groups using multi-detector computed tomography and echocardiography. Results: LA wall remodeling was most predominant and peak atrial longitudinal strain (PALS) was worst in HFpEF+AF patients as compared to the rest. Despite lower E/e' (9.8 ± 3.8 vs. 13.4 ± 6.4) yet comparable LA volume, LAWT and PALS in AF alone vs. HFpEF alone, LAWV [12.6 (11.6–15.3) vs. 12.0 (10.2–13.7); p = 0.01] and LAWT(SD) [0.68 (0.61–0.71) vs. 0.60 (0.56–0.65); p &lt; 0.001] were significantly greater in AF alone vs. HFpEF alone even after multi-variate adjustment and propensity matching. After excluding the HFpEF+AF group, both LAWV and LAWT [SD] provided incremental values when added to PALS or LAVi (all p for net reclassification improvement &lt;0.05) in discriminating AF alone, with LAWT[SD] yielding the largest C-statistic (0.78, 95% CI: 0.70–0.86) among all LA wall indices. Conclusions: Despite a similar extent of LA enlargement and dysfunction in HFpEF vs. AF alone, larger LAWV and LAWT [SD] can distinguish AF from HFpEF alone, suggesting the distinct underlying pathophysiological mechanism of LA remodeling in AF vs. HFpEF.</p

Lobocrassins A–E: New Cembrane-Type Diterpenoids from the Soft Coral Lobophytum crassum

Five new cembrane-type diterpenoids, lobocrassins A–E (1–5), were isolated from the soft coral Lobophytum crassum. The structures of cembranes 1–5 were established by spectroscopic and chemical methods and by comparison of the spectral data with those of known cembrane analogues. Lobocrassin A (1) is the first cembranoid possessing an α-chloromethyl-α-hydroxy-γ-lactone functionality and is the first chlorinated cembranoid from soft corals belonging to the genus Lobophytum. Lobocrassins B (2) and C (3) were found to be the stereoisomers of the known cembranes, 14-deoxycrassin (6) and pseudoplexaurol (7), respectively. Lobocrassin B (2) exhibited modest cytotoxicity toward K562, CCRF-CEM, Molt4, and HepG2 tumor cells and displayed significant inhibitory effects on the generation of superoxide anion and the release of elastase by human neutrophils

Natural Product Chemistry of Gorgonian Corals of Genus Junceella—Part II

The structures, names, bioactivities, and references of 81 new secondary metabolites obtained from gorgonian corals belonging to the genus Junceella are described in this review. All compounds mentioned in this review were obtained from sea whip gorgonian corals Junceella fragilis and Junceella juncea, collected from the tropical and subtropical Indo-Pacific Ocean