<Emphasis Type="Italic">Phialemoniopsis endophytica</Emphasis> sp. nov., a new species of endophytic fungi from <Emphasis Type="Italic">Luffa cylindrica</Emphasis> in Henan,China

During a survey of endophytic fungi in the cucurbit plants collected from Henan, China, a new species, Phialemoniopsis endophytica was isolated from the lower stem of Luffa cylindrica. It differs from other Phialemoniopsis species by its cylindrical to flask-shaped phialides, falcate conidia with blunt ends, ostiolate pycnidium-like conidiomata without marginal setae and ellipsoidal chlamydospores. Multi-locus (ITS, LSU, ACT, and TUB) phylogenetic analysis confirmed that P. endophytica is distinct from other species. A synopsis of the morphological characters of the new species is provided.     

Long-Term Prognostic Analysis after Endoscopic Endonasal Surgery for Olfactory Neuroblastoma: A Retrospective Study of 13 Cases

ObjectivesTo summarize the characteristics and long–term outcomes of olfactory neuroblastoma through the analysis of 13 cases in single institution, with the assessment of treatment modality, prognostic factors.MethodA retrospective study of thirteen cases diagnosed as olfactory neuroblastoma and underwent combined treatments during the period 2000–2010. Statistical analysis was performed to search for prognostic factors and compared different treatment modalities.Results13 patients were enrolled in this study, including 8 male and 5 female, ranging from 15 to 69 (median 43) years old. One patient at stage A was only treated with endoscopic endonasal surgery (EES). Seven patients were treated with preoperative radiotherapy and EES, two with EES and postoperative radiotherapy, and the other three with combined radiotherapy and chemotherapy. The range of follow-up time varied from 23 to 116 months (median 65 months). The 5-year overall survival rate was 46.2% (6/13). To date, these thirteen patients have not suffered local recurrences while two patients had lymph node recurrences and one had distant metastasis in the bone marrow. In 13 patients, 61.5% were diagnosed as late T stage (T3/4), 69.2% late Kadish stage (C/D) and 53.8% were high Hyams grade (I/ II), which indicated poor prognosis. Related prognostic factors were the TNM stage (T stage P = 0.028, N stage P = 0.000, M stage P = 0.007), Kadish stage (P = 0.025) and treatment modality (P = 0.015).ConclusionLate stage of TNM and Kadish staging system indicated a poor prognosis. Combined treatment modality, including endoscopic endonasal surgery, achieved a better outcome than non-surgical approach.     

ssDNA Aptamer Specifically Targets and Selectively Delivers Cytotoxic Drug Doxorubicin to HepG2 Cells

Hepatocellular carcinoma (HCC) is the third leading cause of death due to cancer worldwide with over 500,000 people affected annually. Although chemotherapy has been widely used to treat patients with HCC, alternate modalities to specifically deliver therapeutic cargos to cancer cells have been sought in recent years due to the severe side effects of chemotherapy. In this respect, aptamer-based tumor targeted drug delivery has emerged as a promising approach to increase the efficacy of chemotherapy and reduce or eliminate drug toxicity. In this study, we developed a new HepG2-specific aptamer (HCA#3) by a procedure known as systematic evolution of ligands by exponential enrichment (SELEX) and exploited its role as a targeting ligand to deliver doxorubicin (Dox) to HepG2 cells in vitro. The selected 76-base nucleotide aptamer preferentially bound to HepG2 hepatocellular carcinoma cells but not to control cells. The aptamer HCA#3 was modified with paired CG repeats at the 5′-end to carry and deliver a high payload of intercalated Dox molecules at the CG sites. Four Dox molecules (mol/mol) were fully intercalated in each conjugate aptamer-Dox (ApDC) molecule. Biostability analysis showed that the ApDC molecules are stable in serum. Functional analysis showed that ApDC specifically targeted and released Dox within HepG2 cells but not in control cells, and treatment with HCA#3 ApDC induced HepG2 cell apoptosis but had minimal effect on control cells. Our study demonstrated that HCA#3 ApDC is a promising aptamer-targeted therapeutic that can specifically deliver and release a high doxorubicin payload in HCC cells.     

The Potential Biomarkers to Identify the Development of Steatosis in Hyperuricemia

Hyperuricemia (HU) often progresses to combine with non-alcoholic fatty liver disease (NAFLD) in the clinical scenario, which further exacerbates metabolic disorders; early detection of biomarkers, if obtained during the HU progression, may be beneficial for preventing its combination with NAFLD. This study aimed to decipher the biomarkers and mechanisms of the development of steatosis in HU. Four groups of subjects undergoing health screening, including healthy subjects, subjects with HU, subjects with HU combined with NAFLD (HU+NAFLD) and subjects with HU initially and then with HU+NAFLD one year later (HU→HU+NAFLD), were recruited in this study. The metabolic profiles of all subjects’ serum were analyzed by liquid chromatography quadruple time-of-flight mass spectrometry. The metabolomic data from subjects with HU and HU+NAFLD were compared, and the biomarkers for the progression from HU to HU+NAFLD were predicted. The metabolomic data from HU→HU+NAFLD subjects were collected for further verification. The results showed that the progression was associated with disturbances of phospholipase metabolism, purine nucleotide degradation and Liver X receptor/retinoic X receptor activation as characterized by up-regulated phosphatidic acid, cholesterol ester (18:0) and down-regulated inosine. These metabolic alterations may be at least partially responsible for the development of steatosis in HU. This study provides a new paradigm for better understanding and further prevention of disease progression.     

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.