Generation and Characterization of an Immortalized Human Esophageal Myofibroblast Line

Stromal cells with a myofibroblast phenotype present in the normal human esophagus are increased in individuals with gastro-esophageal reflux disease (GERD). We have previously demonstrated that myofibroblasts stimulated with acid and TLR4 agonists increase IL-6 and IL-8 secretion using primary cultures of myofibroblasts established from normal human esophagus. While primary cultures have the advantage of reflecting the in vivo environment, a short life span and unavoidable heterogeneity limits the usefulness of this model in larger scale in vitro cellular signaling studies. The major aim of this paper therefore was to generate a human esophageal myofibroblast line with an extended lifespan. In the work presented here we have generated and characterized an immortalized human esophageal myofibroblast line by transfection with a commercially available GFP-hTERT lentivirus. Immortalized human esophageal myofibroblasts demonstrate phenotypic, genotypic and functional similarity to primary cultures of esophageal myofibroblasts we have previously described. We found that immortalized esophageal myofibroblasts retain myofibroblast spindle-shaped morphology at low and high confluence beyond passage 80, and express α-SMA, vimentin, and CD90 myofibroblast markers. Immortalized human esophageal myofibroblasts also express the putative acid receptor TRPV1 and TLR4 and retain the functional capacity to respond to stimuli encountered in GERD with secretion of IL-6. Finally, immortalized human esophageal myofibroblasts also support the stratified growth of squamous esophageal epithelial cells in 3D organotypic cultures. This newly characterized immortalized human esophageal myofibroblast cell line can be used in future cellular signaling and co-culture studies.     

Insights into functional genes and taxonomical/phylogenetic diversity of microbial communities in biological heap leaching system and their correlation with functions

Applied Microbiology and Biotechnology - Although the taxonomical/phylogenetic diversity of microbial communities in biological heap leaching systems has been investigated, the diversity of...     

Approximate parameter inference in systems biology using gradient matching: a comparative evaluation

Background

A challenging problem in current systems biology is that of parameter inference in biological pathways expressed as coupled ordinary differential equations (ODEs). Conventional methods that repeatedly numerically solve the ODEs have large associated computational costs. Aimed at reducing this cost, new concepts using gradient matching have been proposed, which bypass the need for numerical integration. This paper presents a recently established adaptive gradient matching approach, using Gaussian processes (GPs), combined with a parallel tempering scheme, and conducts a comparative evaluation with current state-of-the-art methods used for parameter inference in ODEs. Among these contemporary methods is a technique based on reproducing kernel Hilbert spaces (RKHS). This has previously shown promising results for parameter estimation, but under lax experimental settings. We look at a range of scenarios to test the robustness of this method. We also change the approach of inferring the penalty parameter from AIC to cross validation to improve the stability of the method.

Methods

Methodology for the recently proposed adaptive gradient matching method using GPs, upon which we build our new method, is provided. Details of a competing method using RKHS are also described here.

Results

We conduct a comparative analysis for the methods described in this paper, using two benchmark ODE systems. The analyses are repeated under different experimental settings, to observe the sensitivity of the techniques.

Conclusions

Our study reveals that for known noise variance, our proposed method based on GPs and parallel tempering achieves overall the best performance. When the noise variance is unknown, the RKHS method proves to be more robust.

     

西藏维管植物新记录

本研究首次发现西藏新记录属云实属(Caesalpinia Linn.)植物——见血飞(Caesalpinia cucullata Roxb.),另外报道了11个新记录种和2个变种:瓶尔小草科(Ophioglossaceae)薄叶阴地蕨(Botrychium daucifolium Wall.),凤尾蕨科(Pteridaceae)华中凤尾蕨(Pteris kiuschiuensis var.centrochinensis ChingS.H.Wu),毛茛科(Ranunculaceae)尾叶铁线莲(Clematis urophylla Franch.),椴树科(Tiliaceae)刺蒴麻(Triumfetta rhomboidea Jacq.),锦葵科(Malvaceae)拔毒散(Sida szechuensis Matsuda),中华地桃花[Urena lobata var.chinensis(Osbeck)S.Y.Hu],柳叶菜科(Onagraceae)草龙[Ludwigia hyssopifolia(G.Don)Exell]、卵叶丁香蓼(Ludwigia ovalis Miq.),唇形科(Lamiaceae)小鱼仙草[Mosla dianthera(Buch.-Ham.)Maxim.],玄参科(Scrophulariaceae)石龙尾[Limnophila sessiliflora(Vahl)Bl.],爵床科(Acanthaceae)白接骨[Asystasia neesiana(Wall.)Nees],桔梗科(Campanulaceae)卵叶半边莲(Lobelia zeylanica Linn.),天南星科(Araceae)百足藤[Pothos repens(Loureiro)Druce]。研究结果进一步丰富了西藏的植物区系,并为研究与相邻地区植物区系的联系增加了新内容。     

Circulating RNAs as predictive markers for the progression of type 2 diabetes

Type 2 Diabetes Mellitus (T2DM) is the most prevalent form of diabetes in the USA, thus, the identification of biomarkers that could be used to predict the progression from prediabetes to T2DM would be greatly beneficial. Recently, circulating RNA including microRNAs (miRNAs) present in various body fluids have emerged as potential biomarkers for various health conditions, including T2DM. Whereas studies that examine the changes of miRNA spectra between healthy controls and T2DM individuals have been reported, the goal of this study is to conduct a baseline comparison of prediabetic individuals who either progress to T2DM, or remain prediabetic. Using an advanced small RNA sequencing library construction method that improves the detection of miRNA species, we identified 57 miRNAs that showed significant concentration differences between progressors (progress from prediabetes to T2DM) and non‐progressors. Among them, 26 have been previously reported to be associated with T2DM in either body fluids or tissue samples. Some of the miRNAs identified were also affected by obesity. Furthermore, we identified miRNA panels that are able to discriminate progressors from non‐progressors. These results suggest that upon further validation these miRNAs may be useful to predict the risk of conversion to T2DM from prediabetes.     

Phenotypic Characteristics and Fatty Acid Composition of Seeds from Different Herbaceous Peony Species Native to China

Herbaceous peony has been widely cultivated in China due to its substantial ornamental and medicinal value. In the present study, the phenotypic characteristics, total fatty acid (FA) content, and nine FA compositions of herbaceous peony seeds from 14 populations belonging to six species and one subspecies were determined by normal test and gas chromatography/mass spectrometry (GC/MS). The results showed that the phenotypic characteristics of seeds varied dramatically among species. The concentrations of five major FAs in seed oils were as follows: linoleic acid (173.95–236.51 μg/mg), linolenic acid (227.82–302.71 μg/mg), oleic acid (135.32–208.81 μg/mg), stearic acid (6.52–11.7 μg/mg), and palmitic acid (30.67–47.64 μg/mg). Correlation analysis demonstrated that oleic acid had the highest partial correlation coefficient with total FAs and might be applied to develop a model of phenotypic characteristics. FAs were significantly influenced by the following environmental factors: latitude, elevation, and annual average temperature. Based on the FA levels in the seed oils, clustering analysis divided 14 populations into two clusters. It was found that the average contents of oleic acid, linoleic acid, and total FAs in cluster I (147.16 μg/mg, 200.31 μg/mg, and 671.24 μg/mg, respectively) were significantly lower than those in cluster II (196.65 μg/mg, 220.16 μg/mg, and 741.78 μg/mg, respectively). Cluster I was perfectly consistent with subsect. Foliolatae, while cluster II was in good agreement with subsect. Dissectifoliae. Therefore, the FA composition of wild herbaceous peony seed oil might be used as a chemotaxonomic marker.