Mutant p53 and ELK1 co-drive FRA-1 expression to induce metastasis in breast cancer.

Tumor-associated p53 mutations induce activities different from wild-type p53, thus causing loss of the protein's tumor inhibition function. The cells carrying p53 mutations have more aggressive characteristics related to invasion, metastasis, proliferation, and cell survival. By comparing the gene expression profiles of mutant p53 (mutp53) and mutp53 silenced cohorts, we found that FOS-related antigen-1 (FRA-1), which is encoded by FOSL1, is a potential effector of mutp53-mediated metastasis. We demonstrate that the expression of FRA-1, a gatekeeper of mesenchymal-epithelial transition, is elevated in the presence of p53 mutations. Mechanistically, mutant p53 cooperates with the transcription factor ELK1 in binding and activating the promoter of FOSL1, thus fostering lung metastasis. This study reveals new insights into how mutant p53 contributes to metastasis in breast cancer.

Occurrence, genotyping, and health risk of Cryptosporidium and Giardia in recreational lakes in Tianjin, China.

Cryptosporidium and Giardia are critical parasites in the etiology of diarrhea worldwide, and often cause waterborne outbreaks. The presence of Cryptosporidium and Giardia in recreational lakes was investigated with molecular characterization, and a comprehensive quantitative microbial risk assessment (QMRA) of protozoan infections was performed, considering multiple exposure pathways, differences in age, sex, and disease severity, and the genotypes of the protozoa. Forty-three (82.7%) and 51 (98.1%) water samples were positive for Cryptosporidium oocysts and Giardia cysts, respectively, with average counts of 3.65 oocysts/10 L and 12.58 cysts/10 L, respectively. Six Cryptosporidium species and three Giardia lamblia assemblages were confirmed with molecular analyses. The protozoan concentration was significantly associated with water turbidity, but not with the total coliform numbers. Swimming in the lakes entailed the highest incidence risk of 5.72 × 10-4 per person per year (pppy) (95% confidence interval (CI): 0.03-43.33 × 10-4) for Cryptosporidium and 4.04 × 10-4 pppy (95% CI: 0.01-32.66 × 10-4) for Giardia, whereas wading entailed the lowest risk (2.20 × 10-4 and 1.70 × 10-4 pppy, respectively). The annual burdens attributable to recreational-water-associated cryptosporidiosis and giardiasis were 3.44 (95% CI: 0.04-23.51) and 1.81 (95% CI: 0.01-12.96) disability-adjusted life years per 1,000,000 individuals per year, respectively. Children were more likely to have an individual disease burden than adults, and males were more likely than females. Sensitivity analysis highlighted the great importance of controlling the proportion of exposed individuals and reducing the frequency of exposure. The methodology and results of this study will allow us to better evaluate and reduce the burden of Cryptosporidium and/or Giardia infections associated with recreational water use in China and other countries.

Presence and molecular characterization of Cryptosporidium and Giardia in recreational lake water in Tianjin, China: a preliminary study.

Little is known about the occurrence of Cryptosporidium and Giardia in recreational water in China. A total of 52 samples were collected from recreational lakes in Tianjin during a high-occurrence season (June-October) for the waterborne cryptosporidiosis and giardiasis, and the occurrence and genotypes of Cryptosporidium and Giardia were investigated. The results showed that 82.7% (43) and 98.1% (51) of samples were positive for Cryptosporidium oocyst and Giardia cysts, respectively. The mean concentration of parasites was 3.65 oocysts/10 L and 12.58 cysts/10 L, respectively. Molecular characterization revealed that the presence of Cryptosporidium parvum, C. andersoni, C. hominis, C. meleagridis, C. fragile, C. ubiquitum, and Giardia lamblia assemblage A, B and D. The protozoan contamination in the studied lakes may originate from animal feces on ground, which was washed into the lake by stormwater runoff. Nevertheless, there is a potential risk of infection during recreational activities in the lake because the dominant detected protozoan genotypes are common human pathogens. Moreover, microbial indicators analysis does not adequately indicate the protozoan contamination in recreational water. The information from this study will be valuable for future protozoan source tracking, and any further control interventions against Cryptosporidium and/or Giardia infection associated with recreational water.

Influence of sewage treatment plant effluent discharge into multipurpose river on its water quality: A quantitative health risk assessment of Cryptosporidium and Giardia.

Sewage treatment plants (STPs) are one of the sources of pathogens discharged into surface water. An investigation was carried out over the duration of 12 months in Henan Province, China, to evaluate the health influence of municipal wastewater effluent discharge on water quality of the receiving water. A discharge-based quantitative microbial risk assessment (QMRA) was employed, taking into account the vegetables consumption habits of the Chinese, population subgroups with different immune statuses and ages, to evaluate the incremental disease burden from agricultural irrigation and swimming exposure scenarios associated with increased concentration of the protozoan Cryptosporidium and/or Giardia in the receiving river. The results shown that all the STP influent samples contained Cryptosporidium and Giardia with average density of 142.31 oocysts/L and 1187.06 cysts/L, respectively. The QMRA results demonstrated that the estimated additional health burdens due to discharged effluent for both parasites were slightly violated the threshold of 10-6 DALYs per person per year set by WHO. Mitigation measures should be planned and executed by season since more disease burdens were borne during hot season than other seasons. The sensitivity analysis highlighted the great importance of stability of STP treatment process. This study provides useful information to improve the safety of surface water and deduce the disease burden of the protozoa in Henan Province and other region inside and outside China.

Alternative promotion and suppression of metastasis by JNK2 governed by its phosphorylation.

Fos-related antigen 1 (Fra1) has been proposed as a gatekeeper of the mesenchymal-epithelial transition to epithelial-mesenchymal transition. Here, we showed that de-phosphorylated JNK2 increased the expression of Fra1 by promoting the expression of c-Jun and Jun-B. Conversely, phosphorylated JNK2 suppressed its expression via enhancing the ubiquitination of c-Jun and Jun-B. These data provided insights into the regulatory mechanism of JNK2 on the expression of Fra1. Our study thus demonstrated that the conversion of JNK2 from its phosphorylation to de-phosphorylation status promoted the switch of breast cancer cells from mesenchymal-epithelial transition to epithelial-mesenchymal transition.

Occurrence of Cryptosporidium and Giardia and the Relationship between Protozoa and Water Quality Indicators in Swimming Pools.

A total of 60 samples were collected from 35 swimming pools in Beijing, China, and the presence of Cryptosporidium and Giardia were investigated. The results showed that 16.7% and 15.0% of samples were positive for Cryptosporidium oocyst and Giardia cysts, respectively, with a mean concentration of 0.30 oocysts/10 L and 0.27 cysts/10 L. The oocysts and cysts were found to have higher rates of occurrence in August than in May. Genotyping confirmed the presence of Cryptosporidium hominis, C. parvum, and Giardia assemblages A and B, all of which were associated with human infections. The predominant species/assemblages were C. hominis and Giardia assemblage A. Analyses of the relationships between parasite oocysts/cysts, indicator bacteria, and physical-chemical parameters revealed that there was no correlation between 2 parasites and fecal bacterial indicators, whilst there was a significant correlation between protozoa and urea concentration, which indicates that urea concentration rather than fecal bacterial indicators might be an appropriate index for chlorine-resistant protozoa in swimming pools. This study provides useful information to improve the safety of swimming pool water and deduce the risk of protozoan infections.