Post partum depression (PPD) is relatively common in China but its clinical characteristics and risk factors have not been studied. We set out to investigate whether known risk factors for PPD could be found in Chinese women.
A case control design was used to determine the impact of known risk factors for PPD in a cohort of 1970 Chinese women with recurrent DSM-IV major depressive disorder (MDD). In a within-case design we examined the risk factors for PPD in patients with recurrent MDD. We compared the clinical features of MDD in cases with PPD to those without MDD. Odds ratios were calculated using logistic and ordinal regression.
Lower occupational and educational statuses increased the risk of PPD, as did a history of pre-menstrual symptoms, stressful life events and elevated levels of the personality trait of neuroticism. Patients with PPD and MDD were more likely to experience a comorbid anxiety disorder, had a younger age of onset of MDD, have higher levels of neuroticism and dysthymia.
Results obtained in this clinical sample may not be applicable to PPD within the community. Data were obtained retrospectively and we do not know whether the correlations we observe have the same causes as those operating in other populations.
Our results are consistent with the hypothesis that the despite cultural differences between Chinese and Western women, the phenomenology and risk factors for PPD are very similar.
Postpartum depression; Major depressive disorder; Neuroticism; Anxiety disorder
Many types of human tumor cells have overexpressed pyruvate kinase M2 (PKM2). However, the mechanism underlying this increased PKM2 expression remains to be defined. We demonstrate here that EGFR activation induces PLCγ1-dependent PKCε monoubiquitylation at Lys321 mediated by RINCK1 ubiquitin ligase. Monoubiquitylated PKCε interacts with a ubiquitin-binding domain in NEMO zinc finger and recruits the cytosolic IKK complex to the plasma membrane, where PKCε phosphorylates IKKβ at Ser177 and activates IKKβ. Activated RelA interacts with HIF1α, which is required for RelA to bind the PKM2 promoter. PKCε- and NF-κB-dependent PKM2 upregulation is required for EGFR-promoted glycolysis and tumorigenesis. In addition, PKM2 expression correlates with EGFR and IKKβ activity in human glioblastoma specimens and with grade of glioma malignancy. These findings highlight the distinct regulation of NF-κB by EGF, in contrast to TNFα, and the importance of the metabolic cooperation between the EGFR and NF-κB pathways in PKM2 upregulation and tumorigenesis.
EGFR; PKM2; PKCε; NF-κB; RelA; NEMO; IKKβ; HIF1α; monoubiquitylation; phosphorylation; glycolysis; tumorigenesis
The objective of this study was to evaluate the prospective associations between type 2 diabetes mellitus (T2DM) and the risk of periodontitis and tooth loss.
35,247 male participants of the Health Professionals Follow-Up Study who were dentate, free of periodontitis and cancer at baseline, were followed from 1986-2006. Data on self-reported diabetes, periodontitis, tooth loss and potential confounders were collected at baseline and biennially through mailed questionnaires. The multivariable adjusted relationships between diabetes and first report of periodontitis and tooth loss were estimated using time-varying Cox models.
There were 3,009 incident self-reported periodontitis and 10,017 tooth loss events over 591,941 person-years. Men with T2DM showed a 29% (HR=1.29; 95% CI:1.13-1.47) increased risk of periodontitis compared to those without, when adjusted for age, race, smoking, BMI, fruit and vegetable intake, physical activity, alcohol consumption and dental profession. Men with T2DM with total fruit and vegetable intake
Type 2 diabetes mellitus was associated with a significantly greater risk of self-reported periodontitis.
epidemiology; oral disease; type 2 diabetes mellitus; periodontitis
Inflammatory bowel disease (IBD) is commonly treated with thiopurines such as azathioprine and mercaptopurine for the maintenance of remission. Studies examining chemopreventive of these medications on colorectal neoplasm in IBD patients have yielded conflicting results. We performed a meta-analysis to assess the role of thiopurines for this indication.
We performed a systematic search of PubMed, Web of Science, EMBASE and Cochrane to identify studies reporting colorectal neoplasm from IBD patients treated with thiopurines and conducted a meta-analysis of pooled relative risk (RR) using the random effects model.
Nine case-control and ten cohort studies fulfilled the inclusion criteria. The use of thiopurines was associated with a statistically significant decreased incidence of colorectal neoplasm (summary RR=0.71, 95% CI=0.54–0.94, p=0.017), even after adjustment for duration and extent of the disease, but there was high heterogeneity among studies (I2=68.0%, p<0.001). The RR of advanced neoplasm (high-grade dysplasia and cancer) was 0.72 (95%CI=0.50–1.03, p=0.070) and that of cancer was 0.70 (95% CI=0.46–1.09, p=0.111) for thiopurine-treated patients. Heterogeneity of the studies was affected by the sample size (≥100 cases) and whether the patients had longstanding colitis (≥7 years).
The current meta-analysis revealed that thiopurines had a chemopreventive effect of colorectal neoplasms and a tendency of reducing advanced colorectal neoplasms in IBD. Due to the heterogeneity of included studies, these results should be interpreted with caution.
A new class of metal-organic frameworks (MOFs) has been synthesized by ligand-functionalization strategy. Systematic studies of their adsorption properties were performed at low and high pressure. Importantly, when fluorine was introduced into the framework via the functionalization, both the framework stabilities and adsorption capacities towards H2/CO2 were enhanced significantly. This consequence can be well interpreted by theoretical studies of these MOFs structures. In addition, one of these MOFs TKL-107 was used to fabricate mixed matrix membranes, which exhibit great potential for the application of CO2 separation.
The protein deacetylase SIRT1 has been implicated in the regulation of a large number of cellular processes that are thought to be required for cancer initiation and progression. There are conflicting data that make it unclear whether Sirt1 functions as an oncogene or tumor suppressor. To assess the effect of SIRT1 on the emergence and progression of mammary tumors, we crossed mice that harbor a point mutation that abolishes SIRT1 catalytic activity with mice carrying the polyoma middle T transgene driven by the murine mammary tumor virus promoter (MMTV-PyMT). The absence of SIRT1 catalytic activity neither accelerated nor blocked the formation of tumors and metastases in this model. There was a lag in tumor latency that modestly extended survival in Sirt1 mutant mice that we attribute to a delay in mammary gland development and not to a direct effect of SIRT1 on carcinogenesis. These results are consistent with previous evidence suggesting that Sirt1 is not a tumor promoter or a tumor suppressor.
Differential co-expression analysis (DCEA) has emerged in recent years as a novel, systematic investigation into gene expression data. While most DCEA studies or tools focus on the co-expression relationships among genes, some are developing a potentially more promising research domain, differential regulation analysis (DRA). In our previously proposed R package DCGL v1.0, we provided functions to facilitate basic differential co-expression analyses; however, the output from DCGL v1.0 could not be translated into differential regulation mechanisms in a straightforward manner.
To advance from DCEA to DRA, we upgraded the DCGL package from v1.0 to v2.0. A new module named “Differential Regulation Analysis” (DRA) was designed, which consists of three major functions: DRsort, DRplot, and DRrank. DRsort selects differentially regulated genes (DRGs) and differentially regulated links (DRLs) according to the transcription factor (TF)-to-target information. DRrank prioritizes the TFs in terms of their potential relevance to the phenotype of interest. DRplot graphically visualizes differentially co-expressed links (DCLs) and/or TF-to-target links in a network context. In addition to these new modules, we streamlined the codes from v1.0. The evaluation results proved that our differential regulation analysis is able to capture the regulators relevant to the biological subject.
With ample functions to facilitate differential regulation analysis, DCGL v2.0 was upgraded from a DCEA tool to a DRA tool, which may unveil the underlying differential regulation from the observed differential co-expression. DCGL v2.0 can be applied to a wide range of gene expression data in order to systematically identify novel regulators that have not yet been documented as critical.
DCGL v2.0 package is available at http://cran.r-project.org/web/packages/DCGL/index.html or at our project home page http://lifecenter.sgst.cn/main/en/dcgl.jsp.
Aberrant activation of Wnt signaling is frequent in human malignancies. In normal epithelial tissues, including the breast, Wnt signaling is active only in a subset of cells, but it is unknown whether this subset of Wnt signaling-active cells is at increased risk of carcinogenesis. We created transgenic mice (TOP-tva) in which the synthetic Wnt-responsive promoter TOP controlled the gene encoding TVA, which confers susceptibility to infection by the retroviral vector RCAS. Thus, only cells in which Wnt signaling is active will express tva and be targeted by RCAS. Surprisingly, we found that RCAS-mediated delivery of cDNA encoding a constitutively activated version of ErbB2 (HER2/Neu) into the small number of TVA+ mammary epithelial cells in TOP-tva mice failed to induce tumor, while the same virus readily induced mammary tumors after it was delivered into a comparable number of cells in our previously reported mouse line MMTV-tva, whose tva is broadly expressed in mammary epithelium. Furthermore, we could not even detect any early lesions or infected cells in TOP-tva mice at the time of necropsy. Therefore, we conclude that the Wnt pathway-active cell subset in the normal mammary epithelium does not evolve into tumors following ErbB2 activation–rather, they apparently die due to apoptosis, an anticancer “barrier” that we have reported to be erected in some mammary cells followed ErbB2 activation. In accord with these mouse model data, we found that unlike the basal subtype, ErbB2+ human breast cancers rarely involve aberrant activation of Wnt signaling. This is the first report of a defined sub-population of mammalian cells that is “protected” from tumorigenesis by a potent oncogene, and provides direct in vivo evidence that mammary epithelial cells are not equal in their response to oncogene-initiated transformation.
Endometriosis is a chronic disease caused by the presence of endometrial tissue in ectopic locations outside the uterus. Chronic exposure to the environmental pollutant dioxin has been correlated with an increased incidence in the development of endometriosis in non-human primates. We have therefore examined whether there is an association between the polymorphisms of ten dioxin detoxification genes and endometriosis in Japanese women.
This was a pilot study in which 100 patients with endometriosis and 143 controls were enrolled. The prevalence of five microsatellite and 28 single nucleotide polymorphism markers within ten dioxin detoxification genes (AhR, AHRR, ARNT, CYP1A1, CYP2E1, EPHX1, GSTM1, GSTP1, GSTT1, NAT2) was examined.
Taking into account that this analysis was a preliminary study due to its small sample size and genetic power, the results did not show any statistically significant difference between the cases and controls for any of the allele and genotype frequency distributions examined. In addition, no significant associations between the allele/genotype of all polymorphisms and the stage (I–II or III–IV) of endometriosis were observed.
Based on the findings of this pilot study, we conclude the polymorphisms of the ten dioxin detoxification genes analyzed did not contribute to the etiology of endometriosis among our patients.
Electronic supplementary material
The online version of this article (doi:10.1007/s12199-012-0281-y) contains supplementary material, which is available to authorized users.
Endometriosis; Dioxin detoxification genes; Single nucleotide polymorphisms; Microsatellite; Association study
Here, for the first time, we test a novel hypothesis that systemic treatment of stroke with exosomes derived from multipotent mesenchymal stromal cells (MSCs) promote neurovascular remodeling and functional recovery after stroke in rats. Adult male Wistar rats were subjected to 2 hours of middle cerebral artery occlusion (MCAo) followed by tail vein injection of 100 μg protein from MSC exosome precipitates or an equal volume of vehicle phosphate-buffered saline (PBS) (n=6/group) 24 hours later. Animals were killed at 28 days after stroke and histopathology and immunohistochemistry were employed to identify neurite remodeling, neurogenesis, and angiogenesis. Systemic administration of MSC-generated exosomes significantly improved functional recovery in stroke rats compared with PBS-treated controls. Axonal density and synaptophysin-positive areas were significantly increased along the ischemic boundary zone of the cortex and striatum in MCAo rats treated with exosomes compared with PBS control. Exosome treatment significantly increased the number of newly formed doublecortin (a marker of neuroblasts) and von Willebrand factor (a marker of endothelial cells) cells. Our results suggest that intravenous administration of cell-free MSC-generated exosomes post stroke improves functional recovery and enhances neurite remodeling, neurogenesis, and angiogenesis and represents a novel treatment for stroke.
exosome; functional recovery; mesenchymal stromal cell (MSC); microRNA; neurovascular plasticity; stroke
Orthotopic liver transplantation (OLT) is the only proven effective treatment for both end-stage and metabolic liver diseases. Hepatocyte transplantation is a promising alternative for OLT, but the lack of available donor livers has hampered its clinical application. Hepatocyte-like cells (HLCs) differentiated from many multi-potential stem cells can help repair damaged liver tissue. Yet almost suitable cells currently identified for human use are difficult to harvest and involve invasive procedures. Recently, a novel mesenchymal stem cell derived from human menstrual blood (MenSC) has been discovered and obtained easily and repeatedly. In this study, we examined whether the MenSCs are able to differentiate into functional HLCs in vitro. After three weeks of incubation in hepatogenic differentiation medium containing hepatocyte growth factor (HGF), fibroblast growth factor-4 (FGF-4), and oncostain M (OSM), cuboidal HLCs were observed, and cells also expressed hepatocyte-specific marker genes including albumin (ALB), α-fetoprotein (AFP), cytokeratin 18/19 (CK18/19), and cytochrome P450 1A1/3A4 (CYP1A1/3A4). Differentiated cells further demonstrated in vitro mature hepatocyte functions such as urea synthesis, glycogen storage, and indocyanine green (ICG) uptake. After intrasplenic transplantation into mice with 2/3 partial hepatectomy, the MenSC-derived HLCs were detected in recipient livers and expressed human ALB protein. We also showed that MenSC-derived HLC transplantation could restore the serum ALB level and significantly suppressed transaminase activity of liver injury animals. In conclusion, MenSCs may serve as an ideal, easily accessible source of material for tissue engineering and cell therapy of liver tissues.
Menstrual blood-derived mesenchymal stem cell (MenSC); Differentiation; Hepatocyte; Intrasplenic transplantation; Partial hepatectomy
Seasonal associations of cardiovascular mortality have been noted in most populations of European origin years ago, but are not well evaluated in Asian populations recently.
Utilizing the electronic Hospitalization Summary Reports (HSRs) from 32 top-ranked hospitals in Beijing, China, we evaluated the association between winter season and the risk of cardiovascular death among hospitalized individuals. General additive models and logistic regression models were adjusted for confounding factors.
Older patients who were admitted to the hospital in the winter months (January, February, November and December) had a death risk that was increased by approximately 30% to 50% (P < 0.01) over those who were admitted in May. However, younger patients did not seem to experience the same seasonal variations in death risk. The excess winter deaths among older patients were associated with ischemic heart disease (RR = 1.22; 95% CI 1.13 to 1.31), pulmonary heart disease (RR = 1.42; 95% CI 1.10 to 1.83), cardiac arrhythmias (RR = 1.67; 95% CI 1.36 to 2.05), heart failure (RR = 1.30; 95% CI 1.09 to 1.54), ischemic stroke (RR = 1.30; 95% CI 1.17 to 1.43), and other cerebrovascular diseases (RR = 1.78; 95% CI 1.40 to 2.25). The risks of mortality were higher in winter months than in the month of May, regardless of the presence or absence of respiratory disease.
Winter season was associated with a substantially increased risk of cardiovascular death among older Chinese cardiovascular inpatients.
Cardiovascular disease; Winter; Seasonality; Older adults; Mortality; Asian population
Glioma pathogenesis related-2 (GLIPR-2) belongs to pathogenesis related-1 (PR-1) family whose function remains unknown. In our previous studies, GLIPR-2 was found to be a novel potent stimulator of epithelial-to-mesenchymal transition (EMT) in renal fibrosis which has been classified as type 2 EMT. However, whether GLIPR-2 could induce type 3 EMT in carcinogenesis needs further investigation. In this study, we showed that GLIPR-2 was expressed in hepatocellular carcinoma (HCC) tissues, hypoxia could upregulate the expression of GLIPR-2 in HepG2 and PLC/PRF/5 cells in vitro, overexpression of this protein promoted migration and invasion via EMT, knockdown of GLIPR-2 attenuated migration and invasion of HepG2 and PLC/PRF/5 cells in hypoxia. Moreover, extracellular signal-regulated kinases 1 and 2 (ERK1/2) are positively regulated by GLIPR-2. Taken together, we provide evidence for a hypoxia/GLIPR-2/EMT/migration and invasion axis in HCC cells and it provides novel insights into the mechanism of migration and invasion of hepatocellular carcinoma cells in hypoxia condition.
The non-immune binding of immunoglobulins by bacteria is thought to contribute to the pathogenesis of infections. M-related proteins (Mrp) are group A streptococcal (GAS) receptors for immunoglobulins, but it is not known if this binding has any impact on virulence. To further investigate the binding of immunoglobulins to Mrp, we engineered mutants of an M type 4 strain of GAS by inactivating the genes for mrp, emm, enn, sof, and sfbX and tested these mutants in IgG-binding assays. Inactivation of mrp dramatically decreased the binding of human IgG, whereas inactivation of emm, enn, sof, and sfbx had only minor effects, indicating that Mrp is a major IgG-binding protein. Binding of human immunoglobulins to a purified, recombinant form of Mrp indicated that it selectively binds to the Fc domain of human IgG, but not IgA or IgM and that it preferentially bound subclasses IgG1>IgG4>IgG2>IgG3. Recombinant proteins encompassing different regions of Mrp were engineered and used to map its IgG-binding domain to its A-repeat region and a recombinant protein with 3 A-repeats was a better inhibitor of IgG binding than one with a single A-repeat. A GAS mutant expressing Mrp with an in-frame deletion of DNA encoding the A-repeats had a dramatically reduced ability to bind human IgG and to grow in human blood. Mrp exhibited host specificity in binding IgG; human IgG was the best inhibitor of the binding of IgG followed by pig, horse, monkey, and rabbit IgG. IgG from goat, mouse, rat, cow, donkey, chicken, and guinea pig were poor inhibitors of binding. These findings indicate that Mrp preferentially binds human IgG and that this binding contributes to the ability of GAS to resist phagocytosis and may be a factor in the restriction of GAS infections to the human host.
The Chinese population are at an increased risk of autoimmune hepatitis (AIH). The aims of this study were to determine the demographic and clinical features of AIH in China. A total of 83 patients with AIH diagnosed by the revised scoring system were re-analyzed, and the clinical presentations among the different ages were compared. The patients were classified according to age at presentation. AIH occurred in patients aged ≤30 years (9.6%), 31–39 years (10.8%), 40–49 years (16.9%), 50–59 years (31.3%) and ≥60 years (31.3%). There were no differences in the form of the clinical presentation, concurrent autoimmune diseases, cirrhosis distribution and autoantibodies among the groups. However, patients aged ≥60 years presented with higher levels of alkaline phosphatase (ALP) and γ-glutamyl transpeptidase (γ-GT) compared with patients aged ≤30 years (P=0.034, P=0.043, respectively), and patients aged 31–39 years had a significantly lower immunoglobulin G (IgG) level compared with those aged 50–59 years (P=0.049) and those aged ≥60 years (P=0.012). By contrast, patients aged ≤30 years had a significantly higher total bilirubin (TBIL) level compared with those aged 31–39 years (P=0.007), 50–59 years (P=0.002) and ≥60 years (P=0.013). A substantial portion of patients with AIH were aged >60 years, indicating a poor liver-associated outcome under current management strategies. Elderly patients appeared to be more asymptomatic compared with the younger patients.
autoimmune hepatitis; clinical presentation; concurrent autoimmune diseases; China
The aim of this study was to evaluate the simplified and revised scoring systems for the diagnosis of autoimmune hepatitis (AIH). Seventy-seven patients diagnosed with AIH via the revised scoring system were enrolled in this study. Statistical analysis was performed by means of the χ2 test and logistic regression analysis. A total of 39 patients with definite AIH and 38 patients with probable AIH were diagnosed by the revised scoring system, whereas among these 77 patients, the simplified scoring system classified nine cases as definite AIH, 39 as probable AIH and 29 without AIH. In this study, the parameters contributing to the discrepant diagnosis of AIH were compared using the revised and simplified systems. A χ2 test showed that antinuclear antibody (ANA) or smooth muscle antibody (SMA) titers were significantly lower in the patients with discrepant diagnoses (χ2=15.0, P=0.001). Logistic regression with backward selection revealed that for the discrepant diagnosis of patients, the presence of other concurrent autoimmune diseases [odds ratio (OR)=7.25; P=0.018; 95% confidence interval (CI), 1.41–37.29] was the only independent risk factor. In addition, the presence of anti-soluble liver antigen/liver-pancreas antigen (SLA/LP) or perinuclear antineutrophil cytoplasmic antibody (pANCA) (OR=0.12; P=0.022; 95% CI, 0.02–0.74), the level of immunoglobulin G (IgG) with 1–1.1 × Normal (N) (OR=0.02; P=0.044; 95% CI, 0.00–0.89) and ANA or SMA titers ≥1:80 (OR=0.04; P=<0.001; 95% CI, 0.01–0.23) were three independent protective factors. In conclusion, the revised scoring system has a superior performance in the diagnosis of patients with AIH compared with the simplified scoring system. According to the simplified scoring system, other concurrent autoimmune diseases are the risk factor for the AIH diagnosis.
autoimmune hepatitis; Chinese; diagnosis system; evaluation
Cortex Moutan is the root bark of Paeonia suffruticosa Andr. It is the herbal medicine widely used in Traditional Chinese Medicine for the treatment of blood-heat and blood-stasis syndrome. Furthermore, it has been reported that Cortex Moutan has anticancer effect. In this study, the Cortex Moutan extract was evaluated in bladder cancer therapy in vitro and in vivo. Cortex Moutan extract reduces cell viability with IC50 between 1~2 mg/ml in bladder cancer cells, and it has lower cytotoxicity in normal urotheliums. It arrests cells in G1 and S phase and causes phosphatidylserine expression in the outside of cell membrane. It induces caspase-8 and caspase-3 activation and poly(ADP-ribose) polymerase degradation. The pan caspase inhibitor z-VAD-fmk reverses Cortex Moutan-induced cell death. Cortex Moutan also inhibits cell invasion activity in 5637 cells. In mouse orthotopic bladder cancer model, intravesical application of Cortex Moutan decreases the bladder tumor size without altering the blood biochemical parameters. In summary, these results demonstrate the antiproliferation and anti-invasion properties of Cortex Moutan in bladder cancer cells and its antibladder tumor effect in vivo. Cortex Moutan may provide an alternative therapeutic strategy for the intravesical therapy of superficial bladder cancer.
miR-612 suppresses local invasion and distant colonization by directly inhibiting AKT2 in HCC.
MicroRNAs (miRNAs) play a critical role in tumor metastasis. In this study, we identified a set of 32 miRNAs involved in hepatocellular carcinoma (HCC) metastasis. Among them, miR-612 was shown for the first time to have inhibitory effects on HCC proliferation, migration, invasion, and metastasis. AKT2 was verified to be one of the direct targets of miR-612, through which the epithelial–mesenchymal transition (EMT) and metastasis were inhibited. The level of miR-612 in HCC patients was inversely associated with tumor size, stage, EMT, and metastasis. Of particular importance, miR-612 is involved in both the initial and final steps of the metastatic cascade, by suppressing local invasion and distant colonization. The pleiotropic roles of miR-612 in the HCC metastatic cascade suggest that it could be an effective target for both early and advanced HCC.
A Colombian field isolate (SfCOL-wt) of Spodoptera frugiperda multiple nucleopolyhedrovirus (SfMNPV) is a mixture of different genotypes. To evaluate the insecticidal properties of the different genotypic variants, 83 plaque purified virus were characterized. Ten distinct genotypes were identified (named A through J). SfCOL-A was the most prevalent (71±2%; mean ± SE) showing a PstI restriction profile indistinguishable to that of SfCOL-wt. The remaining nine genotypes presented genomic deletions of 3.8 - 21.8 Kb located mainly between nucleotides 11,436 and 33,883 in the reference genome SfMNPV-B, affecting the region between open reading frames (ORFs) sf20 and sf33. The insecticidal activity of each genotype from SfCOL-wt and several mixtures of genotypes was compared to that of SfCOL-wt. The potency of SfCOL-A occlusion bodies (OBs) was 4.4-fold higher than SfCOL-wt OBs, whereas the speed of kill of SfCOL-A was similar to that of SfCOL-wt. Deletion genotype OBs were similarly or less potent than SfCOL-wt but six deletion genotypes were faster killing than SfCOL-wt. The potency of genotype mixtures co-occluded within OBs were consistently reduced in two-genotype mixtures involving equal proportions of SfCOL-A and one of three deletion genotypes (SfCOL-C, -D or -F). Speed of kill and OB production were improved only when the certain genotype mixtures were co-occluded, although OB production was higher in the SfCOL-wt isolate than in any of the component genotypes, or mixtures thereof. Deleted genotypes reduced OB potency but increased OB production of the SfCOL-wt population, which is structured to maximize the production of OBs in each infected host.
Gene expression profiles of Digitaria sanguinalis infected by Curvularia eragrostidis strain QZ-2000 at two concentrations of conidia and two dew durations were analyzed by cDNA amplified fragment length polymorphisms (cDNA-AFLP). Inoculum strength was more determinant of gene expression than dew duration. A total of 256 primer combinations were used for selective amplification and 1214 transcript-derived fragments (TDFs) were selected for their differential expression. Of these, 518 up-regulated differentially expressed TDFs were identified. Forty-six differential cDNA fragments were chosen to be cloned and 35 of them were successfully cloned and sequenced, of which 25 were homologous to genes of known function according to the GenBank database. Only 6 genes were up-regulated in Curvularia eragrostidis-inoculated D. sanguinalis, with functions involved in signal transduction, energy metabolism, cell growth and development, stress responses, abscisic acid biosynthesis and response. It appears that a few pathways may be important parts of the pathogenic strategy of C.
eragrostidis strain QZ-2000 on D. sanguinalis. Our study provides the fundamentals to further study the pathogenic mechanism, screen for optimal C. eragrostidis strains as potential mycoherbicide and apply this product to control D.
The hepatitis C virus (HCV) nonstructural protein 3 (NS3) is essential for the processing of the HCV polyprotein, the replication of HCV RNA, and to short circuit innate immunity signaling. NS3 contains an N-terminal domain with protease activity and a C-terminal domain with helicase activity. The two domains communicate with each other along with other HCV and cellular proteins. Herein we show that RNAs can bind directly to the active site cleft of the NS3 protease domain (NS3P) and inhibit proteolysis of peptide substrates. RNAs that are less apt to form intramolecular structures have a stronger inhibitory activity than RNAs with more stable base paired regions. Two mutations in the protease domain that resulted in decreased affinity to ssRNA were also defective in RNA-induced ATPase activity from the helicase domain of NS3. The coordinated effects on inhibition of protease activity and stimulation of ATPase activity raise the possibility that RNA serves as a regulatory switch for the two processes.
Hepatitis C Virus; positive-strand RNA virus; NS3 protease; nucleic acid inhibitors; RNA binding; ATPase activation