Correction: The bZIP Transcription Factor MoAP1 Mediates the Oxidative Stress Response and is Critical for Pathogenicity of the Rice Blast Fungus Magnaporthe oryzae.

[This corrects the article DOI: 10.1371/journal.ppat.1001302.].

Full-vector multi-mode fiber modeling for short reach serdes links of 112Gbps and beyond.

A rigorous full-vector multi-mode fiber (MMF) model is proposed. It is believed to be the first comparative study of vector and scalar MMF model in terms of differential mode delay (DMD), mode power distribution (MPD), transfer functions as well as eye diagrams. It shows that the vector nature of fiber modes cannot be ignored even though the refractive index difference can be as small as 1%. A standard-compliant methodology for MMF characterization is introduced. The impact of fiber parameters on bandwidth is studied. The statistical transfer function model of OM3 and OM4 fiber is provided. These transfer functions can be applied to the MMF link modeling. Rigorous full-vector MMF model is an essential tool for research and development of MMF link transceivers and standard development of 112Gbps and beyond.

Shared and distinct functions of two Gti1/Pac2 family proteins in growth, morphogenesis and pathogenicity of Magnaporthe oryzae.

Gti1/Pac2 are conserved family proteins that regulate morphogenic transition in yeasts such as Schizosaccharomyces pombe and Candida albicans, and they also control toxin production and pathogenicity in filamentous fungus Fusarium graminearum. To test the functions of Gti1/Pac2 paralogues MoGti1 and MoPac2 in the rice blast fungus Magnaporthe oryzae, we generated respective ΔMogti1 and ΔMopac2 mutant strains. We found that MoGti1 and MoPac2 exhibit shared and distinct roles in hyphal growth, conidiation, sexual reproduction, stress responses, surface hydrophobility, invasive hyphal growth and pathogenicity. Consistent with the putative conserved function of MoGti1, we showed that MoGti1-GFP is localized to the nucleus, whereas MoPac2-GFP is mainly found in the cytoplasm. In addition, we provided evidence that the nuclear localization of MoGti1 could be subject to regulation by MoPmk1 mitogen-activated protein kinase. Moreover, we found that the reduced pathogenicity in the ΔMopac2 mutant corresponds with an increased expression of plant defence genes, including PR1a, AOS2, LOX1, PAD4, and CHT1. Taken together, our studies provide a comprehensive analysis of two similar but distinct Gti1/Pac2 family proteins in M. oryzae, which underlines the important yet conserved functions of these family proteins in plant pathogenic fungi.

The bZIP transcription factor MoAP1 mediates the oxidative stress response and is critical for pathogenicity of the rice blast fungus Magnaporthe oryzae.

Saccharomyces cerevisiae Yap1 protein is an AP1-like transcription factor involved in the regulation of the oxidative stress response. An ortholog of Yap1, MoAP1, was recently identified from the rice blast fungus Magnaporthe oryzae genome. We found that MoAP1 is highly expressed in conidia and during invasive hyphal growth. The Moap1 mutant was sensitive to H2O2, similar to S. cerevisiae yap1 mutants, and MoAP1 complemented Yap1 function in resistance to H2O2, albeit partially. The Moap1 mutant also exhibited various defects in aerial hyphal growth, mycelial branching, conidia formation, the production of extracellular peroxidases and laccases, and melanin pigmentation. Consequently, the Moap1 mutant was unable to infect the host plant. The MoAP1-eGFP fusion protein is localized inside the nucleus upon exposure to H2O2, suggesting that MoAP1 also functions as a redox sensor. Moreover, through RNA sequence analysis, many MoAP1-regulated genes were identified, including several novel ones that were also involved in pathogenicity. Disruption of respective MGG_01662 (MoAAT) and MGG_02531 (encoding hypothetical protein) genes did not result in any detectable changes in conidial germination and appressorium formation but reduced pathogenicity, whereas the mutant strains of MGG_01230 (MoSSADH) and MGG_15157 (MoACT) showed marketed reductions in aerial hyphal growth, mycelial branching, and loss of conidiation as well as pathogenicity, similar to the Moap1 mutant. Taken together, our studies identify MoAP1 as a positive transcription factor that regulates transcriptions of MGG_01662, MGG_02531, MGG_01230, and MGG_15157 that are important in the growth, development, and pathogenicity of M. oryzae.

CircMAN1A2 contributes to nasopharyngeal carcinoma progression via enhancing the ubiquitination of ATMIN through miR-135a-3p/UBR5 axis.

Recently, the dysregulation of circRNAs has been increasingly implicated in the pathogenesis of nasopharyngeal carcinoma (NPC). Among these circRNAs, circMAN1A2 has been highlighted for the up-regulated expression in NPC, whereas the underlying mechanisms have not been clearly established. Thus, the aim of this study was to delineate the tumor-supporting role of circMAN1A2 in the oncogenesis and metastases of NPC. We validated through qRT-PCR that circMAN1A2 was highly expressed in NPC tissues and NPC cells. Survival analysis through Kaplan-Meier method showed that the overall survival, disease-free survival, and distant metastasis-free survival of patients was negatively correlated with the expression of circMAN1A2. Then, gain- and loss-of function assays demonstrated that circMAN1A2 knockdown could impede the proliferation, migration, invasion, and EMT in NPC cells. Further, we conducted dual luciferase reporter gene, RIP, and RNA pull down assays, unveiling that circMAN1A2 functioned as a sponge of miR-135a-3p, and miR-135a-3p targeted UBR5. Additionally, UBR5 interacted with ATMIN to foster the ubiquitination of ATMIN, thereby expediting the malignant behaviors of NPC cells as well as the lung and inguinal lymph node metastases of NPC tumors in vivo. Together, our study uncovered the tumor-initiating and pro-metastatic role of circMAN1A2-miR-135a-3p-UBR5-ATMIN axis in NPC regulation that may be a potential therapeutic target for human NPC.

Long non-coding RNA ZNF667-AS1 retards the development of esophageal squamous cell carcinoma via modulation of microRNA-1290-mediated PRUNE2.

Abnormal long non-coding RNAs (lncRNAs) have been detected in esophageal squamous cell carcinoma (ESCC). Here, we focused on lncRNA ZNF667-AS1 and its downstream mechanism in ESCC progression. Differentially expressed lncRNAs in ESCC were predicted by bioinformatics analysis. ZNF667-AS1, microRNA-1290 (miR-1290), and prune homolog 2 with BCH domain (PRUNE2) expression was determined with their relationship in cell biological processes analyzed also by means of gain- and loss-of-function assays. Xenograft mouse models were performed to re-produce the in vitro findings. We found a decline in ZNF667-AS1 expression in ESCC tissues and cell lines. ZNF667-AS1 overexpression indicated a favorable prognosis of ESCC sufferers. ZNF667-AS1 overexpression suppressed ESCC cell malignant potentials. ZNF667-AS1 reduced miR-1290 to result in upregulation of the miR-1290 target gene PRUNE2. The inhibiting property of ZNF667-AS1 on the malignant characteristics of ESCC cells was achieved by disrupting the miR-1290-mediated downregulation of PRUNE2. ZNF667-AS1 suppressed the tumorigenesis of ESCC in vivo. Collectively, our study demonstrates that ZNF667-AS1 can function as a tumor suppressor in ESCC by upregulating PRUNE2 and downregulating miR-1290.

Effect of inorganic carbon limitation on the conversion of organic carbon to total fatty acids by Monodus subterraneus.

Traditional autotrophic microalgae exhibit low rates of organic carbon assimilation and conversion to useful compounds when switching to mixotrophic or heterotrophic growth. The goal of this study was to investigate the effect of inorganic carbon limitation on the efficiency of organic carbon (glycerol) assimilation and conversion to total fatty acids (TFAs) or the long-chain polyunsaturated fatty acid eicosapentaenoic acid (EPA). An oleaginous Monodus subterraneus was selected and six cultivation conditions were set, including Autotrophy-no aeration, Autotrophy-aeration, Mixotrophy-no aeration, Mixotrophy-no aeration & no Na2CO3, Mixotrophy-aeration, and Heterotrophy. The results showed M. subterraneus could utilize glycerol and grow under mixotrophic condition, while it was not occurred under heterotrophy. Superiority of mixotrophy to autotrophy on biomass productivity was more obvious under inorganic carbon limitation (no aeration or no Na2CO3) than inorganic carbon supply (aeration and existing Na2CO3 in the medium). CO2 limitation (no aeration) decreased content (of dry weight) and production (in medium) of TFAs, which was not evident in mixotrophy. CO2 limitation and inorganic carbon substrate stress largely improved the COD yield of TFAs and EPA under mixotrophic condition. TFA yield (%COD) under Mixotrophy-no aeration & no Na2CO3 was maximum (22.82%), and was almost two-fold higher than that under Mixotrophy-no aeration and nearly three-fold higher than that with Mixotrophy-aeration. EPA yield (% COD) under mixotrophy-no aeration & no Na2CO3 was maximum (6.58%). These results suggested that inorganic carbon limitation is a potentially useful method to enhance conversion of organic carbon to TFAs. Furthermore, the results suggest an application to obtain high value compounds (TFAs or EPA) combined with a high assimilation rate of waste glycerol from biodiesel and epichlorohydrin production by microalgae.

MicroRNA-155 acts as a diagnostic and prognostic biomarker for oesophageal squamous cell carcinoma.

MicroRNA-155 is over-expressed in many human cancers, but researches on its association with malignant oesophageal squamous cell carcinoma (ESCC) are limited. The aim of the present study was to evaluate the potential value of miR-155 as a biomarker for ESCC diagnosis and prognosis. In this study, we found that miR-155 was significantly increased in ESCC tissues compared with the paired adjacent tissues and healthy normal controls (p < .001), according to qRT-PCR, which suggested that miR-155 might act as an oncogene in ESCC. In addition, clinical features such as the depth of tumour invasion, tumour size, and TNM stage were all proved to impact the expression of miR-155 (p < .01). Then, ROC curve analysis, reaching an AUC of 0.870, and a sensitivity and specificity of 83.5% and 77.5%, respectively, revealed that miR-155 was a predictive factor for ESCC. As well, high expression of miR-155 was associated with poor overall survival of the patients (log-rank test, p = .004), according to Kaplan-Meier analysis. MiR-155 might be an independent predictor for overall survival in ESCC patients, manifested by Cox regression analysis (HR = 16.94, 95%CI = 3.33-86.12, p = .001). Taken together, miR-155 could be an independent diagnostic and prognostic biomarker for ESCC.

MoTup1 is required for growth, conidiogenesis and pathogenicity of Magnaporthe oryzae.

The general transcriptional repressor Tup1 proteins play important regulatory roles in the growth and development of fungi. In this report, we characterized MoTup1, a protein homologous to Tup1 of Saccharomyces cerevisiae, from M. oryzae. Disruption of MoTUP1 resulted in severe mycelial growth reduction and a defect in conidiogenesis. We found that MoTup1 is required for the maintenance of cell wall integrity by regulating the expression of the genes involved in cell wall biosynthesis. Pathogenicity assays indicated that the ΔMotup1 mutants lost the ability to invade both rice and barley hosts. Moreover, observation of rice epidermis penetration showed that the hyphal tips of the mutants could still form appressorium-like structures, but were unable to invade host cells. Taken together, our results demonstrate that M. oryzae MoTup1 is an important regulatory factor in fungal growth, development and pathogenesis on hosts.

Association between IRS-2 G1057D polymorphism and risk of gastric cancer.

AIM: To investigate the relationship between insulin receptor substrate-2 (IRS-2) G1057D polymorphism and the risk of gastric cancer (GC) in a Chinese population. METHODS: A case-control study with 197 GC patients and 156 age- and sex- matched control subjects was conducted. The genotypes of polymorphism were assessed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The genotype frequencies of IRS-2 G1057D polymorphism in cases were obviously different from those in the control group (P = 0.031). Compared with GG genotype carriers, the risk for GC was significantly higher (adjusted odds ratio = 2.32, 95% CI: 1.03-5.23, P = 0.042) in the individuals with the IRS-2 DD genotype. Furthermore, stratified analysis was performed based on age, sex, smoking status and residence, but no significant difference between the two groups was found. In addition, no significant association between genotypes and clinicopathological features was observed either. CONCLUSION: This study demonstrates that IRS-2 G1057D is involved in susceptibility to GC, although further large-sample studies are still needed.