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1.  Genomes of the rice pest brown planthopper and its endosymbionts reveal complex complementary contributions for host adaptation 
Genome Biology  2014;15(12):521.
The brown planthopper, Nilaparvata lugens, the most destructive pest of rice, is a typical monophagous herbivore that feeds exclusively on rice sap, which migrates over long distances. Outbreaks of it have re-occurred approximately every three years in Asia. It has also been used as a model system for ecological studies and for developing effective pest management. To better understand how a monophagous sap-sucking arthropod herbivore has adapted to its exclusive host selection and to provide insights to improve pest control, we analyzed the genomes of the brown planthopper and its two endosymbionts.
We describe the 1.14 gigabase planthopper draft genome and the genomes of two microbial endosymbionts that permit the planthopper to forage exclusively on rice fields. Only 40.8% of the 27,571 identified Nilaparvata protein coding genes have detectable shared homology with the proteomes of the other 14 arthropods included in this study, reflecting large-scale gene losses including in evolutionarily conserved gene families and biochemical pathways. These unique genomic features are functionally associated with the animal’s exclusive plant host selection. Genes missing from the insect in conserved biochemical pathways that are essential for its survival on the nutritionally imbalanced sap diet are present in the genomes of its microbial endosymbionts, which have evolved to complement the mutualistic nutritional needs of the host.
Our study reveals a series of complex adaptations of the brown planthopper involving a variety of biological processes, that result in its highly destructive impact on the exclusive host rice. All these findings highlight potential directions for effective pest control of the planthopper.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-014-0521-0) contains supplementary material, which is available to authorized users.
PMCID: PMC4269174  PMID: 25609551
2.  Role of PDGFR-β/PI3K/AKT signaling pathway in PDGF-BB induced myocardial fibrosis in rats 
Objective: To investigate the role of PDGFR-β/PI3K/AKT signaling pathway in the myocardial fibrosis. Methods: CFs were divided into following 4 groups: control group (CON), PDGF-BB group (P), PDGF-BB+IMA group (IMA), and PDGF-BB+LY294002 (LY). Results: Immunofluorescence staining showed about 90% of cells were positive for vimentin and 10% for α-SMA. After incubation for 7 days, fluorescence microscopy revealed more than 90% of cells were positive for α-SMA, which was significantly higher than that in CON group (P < 0.01), but markedly lower than that in IMA group and LY group (P < 0.01). The mRNA and protein expression of PDGFR-β, Col I, Col III, PI3K and Akt increased dramatically at 48 h after PDGF-BB treatment when compared with CON group (P < 0.01). However, IMA and LY294002 significantly inhibited the expression of PDGFR-β and p-PI3K (P < 0.05). In addition, the mRNA expression of PDGFR-β, PI3K and Akt in IMA group and LY group was also markedly lower than those in P group (P < 0.01), and the mRNA and protein expression of Col I and Col III reduced remarkably when compared with P group (P < 0.01). Of note, the mRNA expression of PDGFR-α was comparable among 4 groups, and PDGFR-β expression after PDGF-BB treatment increased significantly when compared with PDGFR-α expression (P < 0.01). Conclusion: PDGF-BB may induce CF proliferation and their transformation into myofibroblasts, which leads to increased synthesis of collagen, resulting in myocardial fibrosis. This is closely associated with PDGFR-β, but not PDGFR-α. PDGFR-β/PI3K/Akt signaling pathway is involved in the PDGF-BB induced myocardial fibrosis.
PMCID: PMC4297339  PMID: 25628782
Myocardial fibrosis; myofibroblasts; platelet-derived growth factor; signaling pathway
3.  Overexpression of EpCAM and Trop2 in pituitary adenomas 
We sought to investigate the expression of EpCAM and Trop2 in Pituitary adenomas (PAs) and study the correlation of protein expression with invasiveness, proliferation, clinical functioning, recurrence/progression, and some other factors. We investigated the expression of EpCAM and Trop2 in 74 samples of PAs by immunohistochemistry and made correlative analysis of protein overexpression with clinicopathological parameters. Follow-up data was analyzed for recurrence/progression with Kaplan-Meier method and Multivariate Cox regression analysis. Immunohistochemistry results showed that overexpression rates of EpCAM and Trop2 were 51/74 (68.9%) and 43/74 (58.1%), respectively. For both EpCAM and Trop2, PAs with invasiveness showed a higher overexpression rate than PAs without invasiveness (PEpCAM = 0.001; PTrop2 = 0.006). Nonfunctional Pituitary adenomas (NFPAs) demonstrated a higher EpCAM overexpression than functional Pituitary adenomas (FPAs) (P = 0.026). Both EpCAM and Trop2 overexpression correlated significantly with expression of proliferation factor Ki-67 (PEpCAM = 0.011; PTrop2 = 0.000), but not with gender and age. Follow-up analysis revealed that Trop2 overexpression was a significantly predictive factor for recurrence/progression by means of Kaplan-Meier method d (P = 0.028) and Multivariate Cox regression analysis (P = 0.025). This study reveals that both EpCAM and Trop2 overexpression in PAs correlate significantly with invasiveness and proliferation. EpCAM presents a potential target for differential diagnosis and immunotherapy for NFPAs. Follow-up analysis shows that Trop2 is a predictive factor for recurrence/progression for PAs.
PMCID: PMC4270592  PMID: 25550831
Pituitary adenomas; EpCAM; Trop2
4.  Genome of a Bombyx mori Nucleopolyhedrovirus Strain Isolated from India 
Journal of Virology  2012;86(21):11941.
Bombyx mori nucleopolyhedrovirus (BmNPV), a member of the Baculoviridae, is a major pathogen of silkworm and has also been recently developed as an expression vector for heterologous gene expression in the silkworm larvae and pupae. To better understand the diversity of this important baculovirus, we sequenced the complete genome of the BmNPV strain isolated from India, where its host is available throughout the year due to its tropical climate. The genome of the Indian strain consists of 127,879 nucleotides, with a G+C content of 40.36%. There are 138 open reading frames (ORFs) encoding the predicted proteins of more than 50 amino acids. Genomic comparison of the Indian strain with 3 other reported BmNPV strains showed that the baculovirus repeat ORFs (bro) and homologous repeat regions (hr's) are highly variable. These results suggest that the BmNPV strain heterogeneity is mainly caused by single-nucleotide polymorphisms (SNPs) and changes in the hr's and bro genes.
PMCID: PMC3486321  PMID: 23043173
5.  Changes in the expression of MMP2, MMP9, and ColIV in stromal cells in oral squamous tongue cell carcinoma: relationships and prognostic implications 
Type IV collagen (ColIV) is the most important scaffold for the basement membrane (BM) proteins, and plays an important role in regulating and limiting tumour invasion and metastasis.
Here, we observed the changes in morphology and distribution of type IV collagen (ColIV) in the basement membrane (BM) surrounding nests of carcinoma in 48 patients with oral tongue squamous cell (OTSCC). We examined the correlation between the expressions of ColIV, MMP-2 and MMP-9 and the prognosis of OTSCC patients. The intensity and patterns of expression were assessed immunohistochemically using anti-human mouse monoclonal MMP-2, MMP-9 and Col IV antibodies. Statistical analyses were performed to determine the prognostic correlations of ColIV, MMP-2, and MMP-9 levels.
MMP-2 and MMP-9 expressions in OTSCC were higher than those in normal oral mucosa and dysplastic oral mucosa group(MMP-2 iOD: 66.40 ± 24.20, 134.69 ± 37.08, and 357.79 ± 116.78; MMP-9 iOD: 88.05 ± 23.85, 307.13 ± 93.22, and 791.31 ± 260.52; in normal, dysplastic oral mucosa, and tumour tissues, respectively, P < 0.01); however, ColIV immunoreactivity was lower (ColIV iOD: 406.87 ± 62.95, 247.83 ± 42.30, and 151.92 ± 38.17 in normal, dysplastic oral mucosa, and tumour tissues, respectively, P < 0.01). High tumour and stromal MMP-2 and MMP-9 expression was significantly associated with positive lymph node status. Col IV expression was associated with positive lymph node status (P < 0.05), and have negatively correlated with the expression of MMP-2 and MMP-9. Overall survival was significantly shorter in patients with high tumour and stromal MMP-2 and MMP-9 expression, and tended to be shorter in patients with low ColIV expression.
Degradation of ColIV was closely related to increased MMP-2 and MMP-9 expression; MMP-9 have more important function than MMP-2 during the cancer development. Monitoring changes in the expression of ColIV, MMP-2, and MMP-9 may be a useful technique for assessing prognoses in OTSCC patients.
PMCID: PMC3490717  PMID: 23107277
Oral tongue squamous carcinoma; MMPs; ColIV; Immunohistochemistry; Prognosis
6.  Golgi Apparatus-Localized Synaptotagmin 2 Is Required for Unconventional Secretion in Arabidopsis 
PLoS ONE  2011;6(11):e26477.
Most secretory proteins contain signal peptides that direct their sorting to the ER and secreted via the conventional ER/Golgi transport pathway, while some signal-peptide-lacking proteins have been shown to export through ER/Golgi independent secretory pathways. Hygromycin B is an aminoglycoside antibiotic produced by Streptomyces hygroscopicus that is active against both prokaryotic and eukaryotic cells. The hygromycin phosphotransferase (HYGR) can phosphorylate and inactivate the hygromycin B, and has been widely used as a positive selective marker in the construction of transgenic plants. However, the localization and trafficking of HYGR in plant cells remain unknown. Synaptotagmins (SYTs) are involved in controlling vesicle endocytosis and exocytosis as calcium sensors in animal cells, while their functions in plant cells are largely unclear.
Methodology/Principal Findings
We found Arabidopsis synaptotagmin SYT2 was localized on the Golgi apparatus by immunofluorescence and immunogold labeling. Surprisingly, co-expression of SYT2 and HYGR caused hypersensitivity of the transgenic Arabidopsis plants to hygromycin B. HYGR, which lacks a signal sequence, was present in the cytoplasm as well as in the extracellular space in HYGR-GFP transgenic Arabidopsis plants and its secretion is not sensitive to brefeldin A treatment, suggesting it is not secreted via the conventional secretory pathway. Furthermore, we found that HYGR-GFP was truncated at carboxyl terminus of HYGR shortly after its synthesis, and the cells deficient SYT2 failed to efficiently truncate HYGR-GFP,resulting in HYGR-GFP accumulated in prevacuoles/vacuoles, indicating that SYT2 was involved in HYGR-GFP trafficking and secretion.
These findings reveal for the first time that SYT2 is localized on the Golgi apparatus and regulates HYGR-GFP secretion via the unconventional protein transport from the cytosol to the extracelluar matrix in plant cells.
PMCID: PMC3225361  PMID: 22140429
7.  Expression of hepatocyte growth factor and its receptor c-Met in human pituitary adenomas 
Neuro-Oncology  2010;12(8):799-803.
Hepatocyte growth factor (HGF) and its receptor c-Met have been known as key determinants of growth and angiogenesis in some brain tumors like gliomas, meningiomas, and schwannomas. But little is known about their expression in pituitary adenomas. In this study, the expression of HGF and c-Met in pituitary adenomas of different histology types was investigated by immunohistochemistry, and correlative analysis of their expression with microvessel density (MVD), Ki-67 expression, and other clinicopathologic factors was made. The results showed that the expression of HGF and c-Met exists in 98% (64 of 65) and 92% (60 of 65) pituitary adenomas, respectively, and co-expression of them existed in 91% (59 of 65) adenomas. HGF had significant correlation with MVD (Spearman's correlation coefficient, r = .31, P = .01) and Ki-67 (r = .32, P = .01). c-Met had significant correlation with MVD (r = .30, P = .02) and Ki-67 (r = .38, P = .00). HGF and c-Met expression had no significant correlation with age or extrasellar extension. There were no significant differences in HGF and c-Met expression between pituitary adenomas of different histology types. The results indicate that HGF and c-Met are widely expressed in pituitary adenomas, and their expression correlates with MVD and Ki-67 expression.
PMCID: PMC2940671  PMID: 20200025
c-Met; hepatocyte growth factor; pituitary adenoma
8.  Influential factors and formation of extrahepatic collateral artery in unresectable hepatocellular carcinoma 
AIM: To analyze the influence factors and formation of extrahepatic collateral arteries (ECAs) in unresectable hepatocellular carcinoma (HCC) with or without chemoe-mbolization.
METHODS: Detailed histories of 35 patients with 39 ECAs of HCC and images including computerized tomography scan, digital subtraction angiography were reviewed carefully to identify ECAs of HCC, ECAs arising from, and anatomic location of tumors in liver. Tumor sizes were measured, and relations of ECAs with times of chemoemb-olization, tumor size, and the anatomic tumor location were analyzed. Complications were observed after chemoemb-olization through ECAs of HCC with different techniques.
RESULTS: Influence factors of formation of ECAs of HCC included the times of repeated chemoembolization, the location of tumors in liver, the tumor size and the types of chemoembolization. ECAs in HCC appeared after 3-4 times of chemoembolization (17.9%), but a higher frequency of ECAs occurred after 5-6 times of chemoem-bolization (56.4%). ECAs presented easily in peripheral areas (71.8%) of liver abutting to the anterior, posterior abdominal walls, the top right of diaphragm and right kidney. ECAs also occurred easily after complete obstruction of the trunk arteries supplying HCCs or the branches of proper hepatic arteries. Extrahepatic collaterals of HCC originated from right internal thoracic (mammary) artery (RITA, 5.1%), right intercostal artery (RICA, 7.7%), left gastric artery (LGA, 12.8%), right inferior phrenic artery (RIPA, 38.5%), omental artery (OTA, 2.6%), superior mesenteric artery (SMA, 23.1%), and right adrenal and renal capsule artery (RARCA, 10.3%), respectively. The complications after chemoembolization attributed to no super selective cathet-erization.
CONCLUSION: The formation of ECAs in unresectable HCC is obviously correlated with multiple chemoembolization, tumor size, types of chemoembolization, anatomic location of tumors. Extrahepatic collaterals in HCC are corresponding to the tumor locations in liver.
PMCID: PMC4305757  PMID: 15849825

Results 1-8 (8)