Inhibitors of Eicosanoid Biosynthesis Influencing the Transcripts Level of sHSP21.4 Gene Induced by Pathogen Infections,in Antheraea pernyi

Small heat shock proteins (sHSPs) can regulate protein folding and protect cells from stress. To investigate the role of sHSPs in the silk-producing insect Antheraea pernyi response to microorganisms, a sHsp gene termed as Ap-sHSP21.4, was identified. This gene encoded a 21.4 kDa protein which shares the conserved structure of insect sHsps and belongs to sHSP21.4 family. Ap-sHSP21.4 was highly expressed in fat body and up-regulated in midgut and fat body of A. pernyi challenged with Escherichia coli, Beauveria bassiana and nuclear polyhedrosis virus (NPV), which was determined by quantitative real-time PCR. Meanwhile, knock down of Ap-sHSP21.4 with dsRNA result in the decrease at the expression levels of several immune response-related genes (defensin, Dopa decarboxylase, Toll1, lysozyme and Kazal-type serine protease inhibitor). Additionally, the impact of eicosanoid biosynthesis on the expression of Ap-sHSP21.4 response to NPV was determined using qPCR, inhibitors of eicosanoid biosynthesis significantly suppress Ap-HSP21.4 expression upon NPV challenge. All together, Ap-sHSP21.4 was involved in the immunity of A. pernyi against microorganism and possibly mediated by eicosanoids pathway. These results will shed light in the understanding of the pathogen-host interaction in A. pernyi.     

Convex-Envelope Based Automated Quantitative Approach to Multi-Voxel 1H-MRS Applied to Brain Tumor Analysis

Background

Magnetic Resonance Spectroscopy (MRS) can measure in vivo brain tissue metabolism that exhibits unique biochemical characteristics in brain tumors. For clinical application, an efficient and versatile quantification method of MRS would be an important tool for medical research, particularly for exploring the scientific problem of tumor monitoring. The objective of our study is to propose an automated MRS quantitative approach and assess the feasibility of this approach for glioma grading, prognosis and boundary detection.

Methods

An automated quantitative approach based on a convex envelope (AQoCE) is proposed in this paper, including preprocessing, convex-envelope based baseline fitting, bias correction, sectional baseline removal, and peak detection, in a total of 5 steps. Some metabolic ratios acquired by this quantification are selected for statistical analysis. An independent sample t-test and the Kruskal-Wallis test are used for distinguishing low-grade gliomas (LGG) and high-grade gliomas (HGG) and for detecting the tumor, peritumoral and contralateral areas, respectively. Seventy-eight cases of pre-operative brain gliomas with pathological reports are included in this study.

Results

Cho/NAA, Cho/Cr and Lip-Lac/Cr (LL/Cr) calculated by AQoCE in the tumor area differ significantly between LGG and HGG, with p≤0.005. Using logistic regression combining Cho/NAA, Cho/Cr and LL/Cr to generate a ROC curve, AQoCE achieves a sensitivity of 92.9%, a specificity of 72.2%, and an area under ROC curve (AUC) of 0.860. Moreover, both Cho/NAA and Cho/Cr in the AQoCE approach show a significant difference (p≤0.019) between tumoral, peritumoral, and contralateral areas. The comparison between the results of AQoCE and Siemens MRS processing software are also discussed in this paper.

Conclusions

The AQoCE approach is an automated method of residual water removal and metabolite quantification. It can be applied to multi-voxel ¹H-MRS for evaluating brain glioma grading and demonstrating characteristics of brain glioma metabolism. It can also detect infiltration in the peritumoral area. Under the limited clinical data used, AQoCE is significantly more versatile and efficient compared to the reference approach of Siemens.     

Pegylated-Interferon Alpha Therapy for Treatment-Experienced Chronic Hepatitis B Patients

Background

Studies are limited on pegylated interferon (Peg-IFN) therapy for chronic hepatitis B (CHB) patients who failed or relapsed on previous antiviral therapy.

Objectives

We aimed to investigate the effect of Peg-IFN therapy in treatment-experienced CHB patients.

Study Design

A total of 57 treatment-experienced CHB patients at two medical centers were enrolled. All of the patients were treated with Peg-IFN α-2a at 180 μg weekly for 24 or 48 weeks. The hepatitis B serological markers and viral loads were tested every 3 months until 1 year after stopping Peg-IFN therapy. The endpoints were HBV DNA <2000IU/mL, hepatitis B e antigen (HBeAg) seroconversion, and a hepatitis B surface antigen (HBsAg) loss at 12 months post-treatment.

Results

In HBeAg-positive patients, 25.0%, 29.2%, and 12.5% of the patients achieved HBeAg seroconversion, HBV DNA <2000 IU/mL and a combined response, respectively, at 12 months post-treatment. Prior IFN therapy, a high baseline ALT level, a low creatinine level, undetectable HBV DNA at 12 weeks and a decline in HBV DNA >2 log₁₀ IU/mL at 12 weeks of therapy were factors associated with treatment response. In HBeAg-negative patients, 9.1%, 15.2%, and 6.1% of the patients achieved undetectable HBV DNA, HBV DNA <2000 IU/mL, and an HBsAg loss, respectively, at 12 months post-treatment. No factor was significantly associated with the treatment response in the HBeAg-negative patients. The median HBsAg level declined from 3.4 to 2.6 log₁₀ IU/mL in all the patients, and the 5-year cumulative rate of the HBsAg loss was 9.8% in the HBeAg-negative patients. Overall, none of the patients prematurely discontinued the Peg-IFN therapy.

Conclusions

Peg-IFN re-treatment is effective for a proportion of HBeAg-positive treatment-experienced patients; it has limited efficacy for HBeAg-negative treatment-experienced patients. Peg-IFN might facilitate HBsAg loss in HBeAg-negative treatment-experienced patients.     

Early faunal successional patterns in artificial reefs used for restoration of impacted biogenic habitats

This study describes the early epifaunal succession associated with an artificial reef constructed to regenerate damaged biogenic habitats formed by Modiolus modiolus (Linnaeus, 1758). Clumps of live M. modiolus were translocated onto three treatments: flattened cultch, elevated cultch, and directly onto the sea floor. Photographic surveys were carried out 1, 6, and 12 months after completion of the experimental array to test the hypothesis that the artificial reef would enhance habitat complexity thus increasing biodiversity and accelerating faunal community succession. These effects were predicted to be greater on elevated cultch due to higher level of protection and greater accessibility to food compared to sea floor treatments. Univariate analysis indicated that after 12 months the artificial reef had developed a significantly richer and more diverse community compared to 1- and 6-month stages. Multivariate analysis revealed a significant temporal shift in species composition from mobile taxa to sessile and interstitial macroinvertebrates as the artificial reef settled. Reef elevation offered no significant advantages for the development of the epifaunal assemblage. Although further regular monitoring is advisable, this study demonstrated that translocation of a foundation species can help restore marine benthic habitats through the development of a diverse community in a relatively short time.     

Spatiotemporal analysis of ground-based woody plant leafing in response to temperature in temperate eastern China

The analysis of woody plant leafing in response to regional-scale temperature variation using ground-based phenology is usually limited by the sparse coverage and missing data of ground observation. In this study, a station-based multispecies method was proposed to generate spatiotemporal variation of woody plant leafing date using ground observations from the Chinese Phenological Observation Network during 1974–1996. The results show that the leafing date had slightly insignificant advance (?0.56 day decade^?1), and the Arctic Oscillation (AO) index could explain 36 % variance of the spring leafing date anomaly. The leafing date had been substantially delayed (4 days) when AO shifted from an extreme high index state (2) in 1989–1990 to a relatively low state (0.1) in 1991–1996. The canonical correlation analysis (CCA) was used to demonstrate the temporal evolutions and spatial structures of interannual variations of the spring temperature and leafing date anomalies. The three CCA spatial patterns of leafing date anomaly are similar to those of spring temperature anomaly. The first spatial pattern shows ubiquitous warming, which is consistent with the ubiquitous advance in leafing date across the study area. The second and third spatial patterns present the regional differences featured by advanced (delayed) leafing associated with high (low) temperature. The results suggest that the spring leafing date anomaly is spatiotemporally coherent with the regional-scale temperature variations. Although we focus here on woody plant leafing in a historical period in temperate eastern China, our station-based multispecies method may be applicable to analysis of the ground-based phenology in response to regional-scale climatic variation in other regions.     

Histone deacetylase1 promotes TGF-β1-mediated early chondrogenesis through down-regulating canonical Wnt signaling

Cartilage formation during both embryonic development and bone repairing processes involves mesenchymal stem cells (MSCs) differentiation. Wnt/β-catenin signaling pathway inhibits early chondrogenesis and is down-regulated during Transforming growth factor-β1 (TGF-β1)-induced chondrogenesis. However, the regulatory molecules that participate in the process is unknown. This study was designed to investigate the underlying mechanisms that down-regulate Wnt/β-catenin pathway during chondrogenesis. TGF-β1-induced micromass cultures of C3H10T1/2 were used as chondrocyte differentiation model. Gene expression profile was detected by realtime-PCR. Regulatory role of HDAC1 on β-catenin was investigated by luciferase assay, chromatin immunoprecipitation (ChIP) assay, co-immunoprecipitation (Co-IP) assay and in vitro ubiquitination assay. In this study, we showed that HDAC1 was induced and suppressed β-catenin gene expression through direct binding to its promoter. Besides, HDAC1 could also interact with deacetylate β-catenin protein through its deacetylase domain, which causes degradation of β-catenin. Our results indicate that HDAC1 plays an important role in chondrogenesis and may represent a therapeutic target for modulation of cartilage development.     

Simulating changes in the leaf unfolding time of 20 plant species in China over the twenty-first century

Recent shifts in phenology reflect the biological response to current climate change. Aiming to enhance our understanding of phenological responses to climate change, we developed, calibrated and validated spatio-temporal models of first leaf date (FLD) for 20 broadleaved deciduous plants in China. Using daily meteorological data from the Chinese Meteorological Administration and the Community Climate System Model, version 3 (CCSM3) created using three IPCC scenarios (A2, A1B and B1), we described the FLD time series of each species over the past 50 years, extrapolating from these results to simulate estimated FLD changes for each species during the twenty-first century. Model validation suggests that our spatio-temporal models can simulate FLD accurately with R ² (explained variance) >0.60. Model simulations show that, from 1952 to 2007, the FLD in China advanced at a rate of ?1.14 days decade^?1 on average. Furthermore, changes in FLD showed noticeable variation between regions, with clearer advances observed in the north than in the south of the country. The model indicates that the advances in FLD observed from 1952–2007 in China will continue over the twenty-first century, although significant differences among species and different climate scenarios are expected. The average trend of FLD advance in China during the twenty-first century is modeled as being ?1.92 days decade^?1 under the A2 scenario, ?1.10 days decade^?1 under the A1B scenario and ?0.74 days decade^?1 under the B2 scenario. The spatial pattern of FLD change for the period 2011–2099 is modeled as being similar but showing some difference from patterns in the 1952–2007 period. At the interspecific level, early-leafing species were found to show a greater advance in FLD, while species with larger distributions tended to show a weaker advance in FLD. These simulated changes in phenology may have significant implications for plant distribution as well as ecosystem structure and function.     

Degradation of phenanthrene by the endophytic fungus <Emphasis Type="Italic">Ceratobasidum stevensii</Emphasis> found in <Emphasis Type="Italic">Bischofia polycarpa</Emphasis>

Some strains of white rot fungi, non-lignolytic fungi and litter-decomposing basidiomycetes have been recognized as PAH degraders. The purpose of our research was to enlarge the scope of PAH-degrading fungi and explore the huge endophytic microorganism resource for bioremediation of PAHs. In this study, phenanthrene was used as a model PAHs compound. Nine strains of endophytic fungi isolated from four kinds of plant from Eupharbiaceae were screened for degradation of phenanthrene. The endophytic fungus Ceratobasidum stevensii (strain B6) isolated from Bischofia polycarpam showed high degradation efficiency and was selected for further studies. Into the fungal culture, 100 mg l⁻¹ phenanthrene was added, and after 10 days of incubation, about 89.51% of the phenanthrene was removed by strain B6. Extracellular ligninolytic enzyme activities of strain B6 were tested. The results showed that manganese peroxidase [MnP] was the predominant ligninolytic enzyme and that its production was greatly induced by the presence of phenanthrene. To confirm the involvement of MnP in phenanthrene degradation, promotion and inhibition studies on MnP in different concentration level of Mn²⁺ and NaN₃ were performed. Additionally, fungal mycelium-free and resuspended experiments were carried out. The results showed no apparent correlation between MnP activity and phenanthrene degradation. The mycelium and fresh medium were the crucial factors affecting the degradation of phenanthrene. To date, this is the first report on PAH degradation by Ceratobasidum stevensii. This study suggests that endophytic fungi might be a novel and important resource for microorganisms that have PAH-degrading capabilities.     

Cytokeratin expression during mouse embryonic and early postnatal mammary gland development

Cytokeratins are intermediate filament proteins found in most epithelial cells including the mammary epithelium. Specific cytokeratin expression has been found to mark different epithelial cell lineages and also to associate with putative mammary stem/progenitor cells. However, a comparative analysis of the expression of cytokaratins during embryonic and postnatal mammary development is currently lacking. Moreover, it is not clear whether the different classes of putative mammary stem/progenitor cells exist during embryonic development. Here, we use double/triple-label immunofluorescence and immunohistochemistry to systematically compare the expression of cytokeratin 5 (K5), cytokeratin 6 (K6), cytokeratin 8 (K8), cytokeratin 14 (K14) and cytokeratin 19 (K19) in embryonic and early postnatal mouse mammary glands. We show that K6⁺ and K8⁺/K14⁺ putative mammary progenitor cells arise during embryogenesis with distinct temporal and spatial distributions. Moreover, we describe a transient disconnection of the expression of K5 and K14, two cytokeratins that are often co-expressed, during the first postnatal weeks of mammary development. Finally, we report that cytokeratin expression in cultured primary mammary epithelial cells mimics that during the early stages of postnatal mammary development. These studies demonstrate an embryonic origin of putative mammary stem/progenitor cells. Moreover, they provide additional insights into the use of specific cytokeratins as markers of mammary epithelial differentiation, or the use of their promoters to direct gene overexpression or ablation in genetic studies of mouse mammary development.     

Antioxidant and antiproliferative activities of hydroxyl-substituted Schiff bases

Eight hydroxyl-substituted Schiff bases with the different number and position of hydroxyl group on the two asymmetric aromatic rings (A and B rings) were prepared by the reaction between the corresponding aromatic aldehyde and aniline. Their antioxidant effects against the stable galvinoxyl radical (GO) in ethyl acetate and methanol, and 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH)-induced DNA strand breakage, and their antiproliferative effects on human hepatoma HepG2 cells, were investigated. Structure–activity relationship analysis demonstrates that o-dihydroxyl groups on the aromatic A ring and 4-hydroxyl group attached to the aromatic B ring contribute critically to the antioxidant and antiproliferative activities.