Antigenic cross-reactivity between severe acute respiratory syndrome-associated coronavirus and human coronaviruses 229E and OC43

Cross-reactivity between antibodies to different human coronaviruses (HCoVs) has not been systematically studied. By use of Western blot analysis, indirect immunofluorescence assay (IFA), and enzyme-linked immunosorbent assay (ELISA), antigenic cross-reactivity between severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) and 2 HCoVs (229E and OC43) was demonstrated in immunized animals and human serum. In 5 of 11 and 10 of 11 patients with SARS, paired serum samples showed a ≥4-fold increase in antibody titers against HCoV-229E and HCoV-OC43, respectively, by IFA. Overall, serum samples from convalescent patients who had SARS had a 1-way cross-reactivity with the 2 known HCoVs. Antigens of SARS-CoV and HCoV-OC43 were more cross-reactive than were those of SARS-CoV and HCoV-229E. © 2005 by the Infectious Diseases Society of America. All rights reserved.published_or_final_versio

Male germ cell-specific protein Trs4 binds to multiple proteins

Temperature-related sequence 4 (Trs4) has been identified as a testis-specific gene with expression sensitive to the abdominal temperature changes induced by artificial cryptorchidism. In murine testes, Trs4 mRNA was detected in round spermatids and its protein was localized mainly in the elongating spermatids as well as in the acrosomes and tails of mature spermatozoa. Using a yeast two-hybrid screening system, we identified Rshl-2, Gstmu1, and Ddc8 as putative binding partners of the Trs4 protein in mouse testes. Their interactions were confirmed by in vivo and in vitro binding assays. Further studies demonstrated that Ddc8, a newly identified gene with unknown functions, displayed a similar expression pattern with Trs4 in mouse testes. In particular, Trs4, Ddc8, and Rshl-2 proteins were co-localized to the tails of mature spermatozoa. These results suggested that Trs4 might be involved in diverse processes of spermiogenesis and/or fertilization through interactions with its multiple binding partners. © 2009 Elsevier Inc.postprin

Systemic delivery of microRNA-101 potently inhibits hepatocellular carcinoma in vivo by repressing multiple targets

Targeted therapy based on adjustment of microRNA (miRNA)s activity takes great promise due to the ability of these small RNAs to modulate cellular behavior. However, the efficacy of miR-101 replacement therapy to hepatocellular carcinoma (HCC) remains unclear. In the current study, we first observed that plasma levels of miR-101 were significantly lower in distant metastatic HCC patients than in HCCs without distant metastasis, and down-regulation of plasma miR-101 predicted a worse disease-free survival (DFS, P<0.05). In an animal model of HCC, we demonstrated that systemic delivery of lentivirus-mediated miR-101 abrogated HCC growth in the liver, intrahepatic metastasis and distant metastasis to the lung and to the mediastinum, resulting in a dramatic suppression of HCC development and metastasis in mice without toxicity and extending life expectancy. Furthermore, enforced overexpression of miR-101 in HCC cells not only decreased EZH2, COX2 and STMN1, but also directly down-regulated a novel target ROCK2, inhibited Rho/Rac GTPase activation, and blocked HCC cells epithelial-mesenchymal transition (EMT) and angiogenesis, inducing a strong abrogation of HCC tumorigenesis and aggressiveness both in vitro and in vivo. These results provide proof-of-concept support for systemic delivery of lentivirus-mediated miR-101 as a powerful anti-HCC therapeutic modality by repressing multiple molecular targets. © 2015 Zheng et al.published_or_final_versio

EZH2 protein: A promising immunomarker for the detection of hepatocellular carcinomas in liver needle biopsies

Background and aims: A previous study of ours indicated that enhancer of zeste homologue 2 (EZH2) plays an important role in hepatocellular carcinoma (HCC) tumorigenesis. The aim of the present study was to investigate the potential diagnostic utility of EZH2 in HCC. Methods: Immunohistochemistry was performed to examine the expression dynamics of EZH2 in two independent surgical cohorts of HCC and non-malignant liver tissues to develop a diagnostic yield of EZH2, HSP70 and GPC3 for HCC detection. The diagnostic performances of EZH2 and a three-marker panel in HCC were re-evaluated by using an additional biopsy cohort. Results: Immunohistochemistry analysis demonstrated that the sensitivity and specificity of EZH2 for HCC detection was 95.8% and 97.8% in the testing cohort. Similar results were confirmed in the validation cohort. For diagnosis of well-differentiated HCCs, the sensitivity and specificity were 68.9% and 91.5% for EZH2, 62.5% and 98.5% for HSP70, 50.0% and 92.1% for GPC3, and 75.0% and 100% for a three-marker panel. In biopsies, positive cases for at least one marker increased from large regenerative nodule and hepatocellular adenoma (0/12) to focal nodular hyperplasia (2/20), dysplastic nodule (7/25), well-differentiated HCC (16/18) and moderately and poorly differentiated HCC (54/54). When at least two positive markers were considered, regardless of their identity, the positive cases were detected in 0/12 large regenerative nodules and hepatocellular adenomas, 0/20 focal nodular hyperplasias, 0/25 dysplastic nodules, 11/18 well-differentiated HCCs, 32/37 moderately differentiated HCCs and 15/17 poorly differentiated HCCs. Conclusion: Our findings suggest that EZH2 protein, as examined by immunohistochemistry, may serve as a promising diagnostic biomarker of HCCs, and the use of a three-marker panel (EZH2, HSP70 and GPC3) can improve the rate of detection of HCCs in liver biopsy tissues.published_or_final_versio

Clinicopathologic characteristics and prognostic factors of ovarian fibrosarcoma: the results of a multi-center retrospective study

<p>Abstract</p> <p>Background</p> <p>Ovarian fibrosarcomas are very rare tumors, and therefore, few case studies have evaluated the prognostic factors of this disease. To our knowledge, this study represents the largest study to evaluate the clinical and pathologic factors associated with ovarian fibrosarcoma patients.</p> <p>Methods</p> <p>Thirty-one cases of ovarian fibrosarcoma were retrospectively reviewed, which included medical records for eight patients, and 23 published case reports from 1995 through 2009. Patient treatment regimens included total hysterectomy with bilateral adnexectomy and an omentectomy (BAO) (n = 9), oophorectomy (OR) (n = 8), chemotherapy (CT) (n = 1), BAO followed by chemotherapy (BAO+CT) (n = 11), BAO followed by radiotherapy (BAO+RT) (n = 1), and oophorectomy followed by radiotherapy (OR + RT) (n = 1).</p> <p>Results</p> <p>The patients of this cohort were staged according to the guidelines of the Federation of Gynecology and Obstetrics (FIGO), with 15, 6, 9, and 1 stage I-IV cases identified, respectively. Mitotic count values were also evaluated from 10 high-power fields (HPFs), and 3 cases had an average mitotic count < 4, 18 cases were between 4 and 10, and 10 cases had an average mitotic count value ≥ 10. The Ki-67 (MIB-1) proliferation index values were grouped according to values that as follows: < 10% (n = 5), between 10% and 50% (n = 9), and ≥ 50% (n = 5). Positive expression of vimentin (100%, 22/22) and negative expression of CD117 (0%, 5/5) were also detected. Moreover, expression of smooth muscle actin (2/18), desmin (1/13), epithelial membrane antigen (0/11), S-100 (1/19), CD99 (0/6), CD34 (1/5), α-inhibin (7/15), estrogen receptor (1/6), and progesterone receptor (1/6) were reported for subsets of the cases examined. After a median follow-up period of 14 months (range, 2-120), the 2-year overall survival rates (OS) and disease-free survival (DFS) rates for all patients were 55.9% and 45.4%, respectively. Cox proportional hazard regression analysis of survival showed that FIGO stage (<it>P </it>= 0.007) and treatment (<it>P </it>= 0.008) were predictive of poor prognosis. Furthermore, patients with stage I tumors that received BAO+CT were associated with a better prognosis.</p> <p>Conclusions</p> <p>Mitotic activity, and cells positive for Ki-67 were identified as important factors in the diagnosis of ovarian fibrosarcoma. Furthermore, FIGO stage and treatment modalities have the potential to be prognostic factors of survival, with BAO followed by adjuvant chemotherapy associated with an improved treatment outcome.</p

Structural evolution of GeMn/Ge superlattices grown by molecular beam epitaxy under different growth conditions

GeMn/Ge epitaxial 'superlattices' grown by molecular beam epitaxy with different growth conditions have been systematically investigated by transmission electron microscopy. It is revealed that periodic arrays of GeMn nanodots can be formed on Ge and GaAs substrates at low temperature (approximately 70°C) due to the matched lattice constants of Ge (5.656 Å) and GaAs (5.653 Å), while a periodic Ge/GeMn superlattice grown on Si showed disordered GeMn nanodots with a large amount of stacking faults, which can be explained by the fact that Ge and Si have a large lattice mismatch. Moreover, by varying growth conditions, the GeMn/Ge superlattices can be manipulated from having disordered GeMn nanodots to ordered coherent nanodots and then to ordered nanocolumns

Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay

The decay channel $\psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p})$ is studied using a sample of $1.06\times 10^8$ $\psi^\prime$ events collected by the BESIII experiment at BEPCII. A strong enhancement at threshold is observed in the $p\bar{p}$ invariant mass spectrum. The enhancement can be fit with an $S$-wave Breit-Wigner resonance function with a resulting peak mass of $M=1861^{+6}_{-13} {\rm (stat)}^{+7}_{-26} {\rm (syst)} {\rm MeV/}c^2$ and a narrow width that is $\Gamma<38 {\rm MeV/}c^2$ at the 90% confidence level. These results are consistent with published BESII results. These mass and width values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics

Population genetic structure of the malaria vector Anopheles nili in sub-Saharan Africa

<p>Abstract</p> <p>Background</p> <p><it>Anopheles nili </it>is a widespread efficient vector of human malaria parasites in the humid savannas and forested areas of sub-Saharan Africa. Understanding <it>An. nili </it>population structure and gene flow patterns could be useful for the development of locally-adapted vector control measures.</p> <p>Methods</p> <p>Polymorphism at eleven recently developed microsatelitte markers, and sequence variation in four genes within the 28s rDNA subunit (ITS2 and D3) and mtDNA (COII and ND4) were assessed to explore the level of genetic variability and differentiation among nine populations of <it>An. nili </it>from Senegal, Ivory Coast, Burkina Faso, Nigeria, Cameroon and the Democratic Republic of Congo (DRC).</p> <p>Results</p> <p>All microsatellite loci successfully amplified in all populations, showing high and very similar levels of genetic diversity in populations from West Africa and Cameroon (mean Rs = 8.10-8.88, mean He = 0.805-0.849) and much lower diversity in the Kenge population from DRC (mean Rs = 5.43, mean He = 0.594). Bayesian clustering analysis of microsatellite allelic frequencies revealed two main genetic clusters in the dataset. The first one included only the Kenge population and the second grouped together all other populations. High Fst estimates based on microsatellites (Fst > 0.118, P < 0.001) were observed in all comparisons between Kenge and all other populations. By contrast, low Fst estimates (Fst < 0.022, P < 0.05) were observed between populations within the second cluster. The correlation between genetic and geographic distances was weak and possibly obscured by demographic instability. Sequence variation in mtDNA genes matched these results, whereas low polymorphism in rDNA genes prevented detection of any population substructure at this geographical scale.</p> <p>Conclusion</p> <p>Overall, high genetic homogeneity of the <it>An. nili </it>gene pool was found across its distribution range in West and Central Africa, although demographic events probably resulted in a higher level of genetic isolation in the marginal population of Kenge (DRC). The role of the equatorial forest block as a barrier to gene flow and the implication of such findings for vector control are discussed.</p

The Characteristics of Blood Glucose and WBC Counts in Peripheral Blood of Cases of Hand Foot and Mouth Disease in China: A Systematic Review

Background: Outbreaks of Hand Foot and Mouth Disease (HFMD) have occurred in many parts of the world especially in China. We aimed to summarize the characteristics of the levels of blood glucose and white blood cell (WBC) counts in cases of HFMD in Mainland China and Taiwan, using meta-analysis based on systematic review of published articles. Methods: We systematically reviewed published studies, from the MEDLINE and WANFANG Data, about the levels of blood glucose and WBC counts in cases of HFMD until 15 th June 2011, and quantitatively summarized the characteristics of them using meta-analysis. Results: In total, 37 studies were included in this review. In Mainland China and Taiwan, generally, the average level of blood glucose, the prevalence of hyperglycemia, WBC counts and the prevalence of leukocytosis increased with the severity of the illness. There was no significant difference in the prevalence of leukocytosis between ANS (autonomic nervous system dysregulation)/PE (pulmonary edema) group and CNS (central nervous system) group, and in the average level of blood glucose between healthy controls and mild cases of HFMD. WBC counts in cases infected by EV71 were less than those in cases infected by CA16. Conclusions: our analyses indicated that blood glucose and WBC counts increased with the severity of HFMD disease, which would help doctors to manage patients efficiently

Identifying Schistosoma japonicum Excretory/Secretory Proteins and Their Interactions with Host Immune System

Schistosoma japonicum is a major infectious agent of schistosomiasis. It has been reported that large number of proteins excreted and secreted by S. japonicum during its life cycle are important for its infection and survival in definitive hosts. These proteins can be used as ideal candidates for vaccines or drug targets. In this work, we analyzed the protein sequences of S. japonicum and found that compared with other proteins in S. japonicum, excretory/secretory (ES) proteins are generally longer, more likely to be stable and enzyme, more likely to contain immune-related binding peptides and more likely to be involved in regulation and metabolism processes. Based on the sequence difference between ES and non-ES proteins, we trained a support vector machine (SVM) with much higher accuracy than existing approaches. Using this SVM, we identified 191 new ES proteins in S. japonicum, and further predicted 7 potential interactions between these ES proteins and human immune proteins. Our results are useful to understand the pathogenesis of schistosomiasis and can serve as a new resource for vaccine or drug targets discovery for anti-schistosome