XPC promotes MDM2-mediated degradation of the p53 tumor suppressor

Although ubiquitin receptor Rad23 has been implicated in bringing ubiquitylated p53 to the proteasome, how Rad23 recognizes p53 remains unclear. We demonstrate that XPC, a Rad23-binding protein, regulates p53 turnover. p53 protein in XPC-deficient cells remains ubiquitylated, but its association with the proteasome is drastically reduced, indicating that XPC regulates a postubiquitylation event. Furthermore, we found that XPC participates in the MDM2-mediated p53 degradation pathway via direct interaction with MDM2. XPC W690S pathogenic mutant is specifically defective for MDM2 binding and p53 degradation. p53 is known to become stabilized following UV irradiation but can be rendered unstable by XPC overexpression, underscoring a critical role of XPC in p53 regulation. Elucidation of the proteolytic role of XPC in cancer cells will help to unravel the detailed mechanisms underlying the coordination of DNA repair and proteolysis.     

IGF1(CA)19 and IGFBP-3-202A/C Gene Polymorphism and Cancer Risk: A Meta-analysis

Insulin-like growth factor 1 (IGF1)(CA)19 and insulin-like growth factor-binding protein-3 (IGFBP-3)-202A/C gene polymorphisms had been focused by many epidemiological studies recently, which were associated with common cancer risk including colorectal, breast, prostate, and lung cancer. However, the findings of epidemiological investigations are not coincident. We did a systematic review and meta-analysis of case–control studies, including studies nested in cohorts, of the association between IGF1(CA)19 and IGFBP-3-202A/C gene polymorphism and prostate, colorectal, premenopausal and postmenopausal breast cancer. We identified 17 eligible studies (24 datasets), which included 9,744 cases and 11,332 controls. The result displays that individuals carrying (CA)19 allele had a subtly decreased risk of all cancer sites [OR(95 % CI) 0.92(0.87,0.97); 0.882(0.809,0.962); 0.902(0.849,0.958)] and postmenopausal breast cancer [OR(95 % CI) 0.893(0.832,0.959); 0.834(0.719,0.968); 0.862(0.776,0.958)] in allele contrast model, CA19/CA19 vs. non-CA19/non-CA19 model, and recessive genetic model. In subgroup analysis according to ethnicities, (CA)19 repeat polymorphism had an increased risk of common cancers in Asian [OR (95 % CI) of allele contrast model: 1.105(1.000,1.224); additive model: 1.103(0.844,1.441), 1.197(1.013,1.413); recessive model: 1.039(0.831,1.300); and dominant model: 1.191(1.030,1.376)]. On the other hand, IGFBP-3-202A/C gene polymorphism did not seem to be associated with all the cancer sites in any genetic model and ethnicity. In conclusion, the result of this meta-analysis indicates that the IGF1(CA)19 polymorphism is a candidate gene polymorphism for cancer susceptibility regardless of environmental factors, especially in Asian.     

Intercropping Enhances Productivity and Maintains the Most Soil Fertility Properties Relative to Sole Cropping

Yield and nutrient acquisition advantages are frequently found in intercropping systems. However, there are few published reports on soil fertility in intercropping relative to monocultures. A field experiment was therefore established in 2009 in Gansu province, northwest China. The treatments comprised maize/faba bean, maize/soybean, maize/chickpea and maize/turnip intercropping, and their correspoding monocropping. In 2011 (the 3^rd year) and 2012 (the 4^th year) the yields and some soil chemical properties and enzyme activities were examined after all crop species were harvested or at later growth stages. Both grain yields and nutrient acquisition were significantly greater in all four intercropping systems than corresponding monocropping over two years. Generally, soil organic matter (OM) did not differ significantly from monocropping but did increase in maize/chickpea in 2012 and maize/turnip in both years. Soil total N (TN) did not differ between intercropping and monocropping in either year with the sole exception of maize/faba bean intercropping receiving 80 kg P ha⁻¹ in 2011. Intercropping significantly reduced soil Olsen-P only in 2012, soil exchangeable K in both years, soil cation exchangeable capacity (CEC) in 2012, and soil pH in 2012. In the majority of cases soil enzyme activities did not differ across all the cropping systems at different P application rates compared to monocrops, with the exception of soil acid phosphatase activity which was higher in maize/legume intercropping than in the corresponding monocrops at 40 kg ha⁻¹ P in 2011. P fertilization can alleviate the decline in soil Olsen-P and in soil CEC to some extent. In summary, intercropping enhanced productivity and maintained the majority of soil fertility properties for at least three to four years, especially at suitable P application rates. The results indicate that maize-based intercropping may be an efficient cropping system for sustainable agriculture with carefully managed fertilizer inputs.     

Evolutionary history of a widespread tree species Acer mono in East Asia

East Asia has the most diverse temperate flora in the world primarily due to the lack of Pleistocene glaciation and the geographic heterogeneity. Although increasing phylogeography studies in this region provided more proofs in this issue, discrepancies and uncertainty still exist, especially in northern temperate deciduous broad‐leaved and coniferous mixed forest region (II). And a widespread plant species could reduce the complexity to infer the relationship between diversity and physiographical pattern. Hence, we studied the evolution history of a widespread temperate tree, Acer mono, populations in region II and the influence of physiographic patterns on intraspecific genetic diversity. Analyses of chloroplast sequences and nuclear microsatellites indicated high levels of genetic diversity. The diversity distribution was spatially heterogeneous and a latitudinal cline existed in both markers. The spatial distribution pattern between genetic diversity within A. mono and the diversity at species level was generally consistent. Western subtropical evergreen broad‐leaved forest subregion (IVb) had a unique ancient chloroplast clade (CP3) and a nuclear gene pool (GP5) with dominance indicating the critical role of this area in species diversification. Genetic data and ecological niche model results both suggested that populations in region II disappeared during the last glacial maximum (LGM) and recovered from south of Changbai Mt. and the Korean Peninsula. Two distribution centers were likely during the LGM, one in the north edge of warm temperate deciduous broad‐leaved forest region (III) and another in the south edge of region III. This was reflected by the genetic pattern with two spatially independent genetic groups. This study highlights the key role of region III in sustaining genetic diversity in the northern range and connecting diversity between southern and northern range. We elucidated the diversity relationship between vegetation regions which could facilitate the understanding of biodiversity origin and maintenance in East Asia.     

Aryl hydrocarbon receptor activation by Lactobacillus reuteri tryptophan metabolism alleviates Escherichia coli-induced mastitis in mice

The intestinal microbiota has been associated with the occurrence and development of mastitis, which is one of the most serious diseases of lactating women and female animals, but the underlying mechanism has not yet been elucidated. Aryl hydrocarbon receptor (AhR) activation by microbiota tryptophan metabolism-derived ligands is involved in maintaining host homeostasis and resisting diseases. We investigated whether AhR activation by microbiota-metabolic ligands could influence mastitis development in mice. In this study, we found that AhR activation using Ficz ameliorated mastitis symptoms, which were related to limiting NF-κB activation and enhancing barrier function. Impaired AhR activation by disturbing the intestinal microbiota initiated mastitis, and processed Escherichia coli (E. coli)-induced mastitis in mice. Supplementation with dietary tryptophan attenuated the mastitis, but attenuation was inhibited by the intestinal microbiota abrogation, while administering tryptophan metabolites including IAld and indole but not IPA, rescued the tryptophan effects in dysbiotic mice. Supplementation with a Lactobacillus reuteri (L. reuteri) strain with the capacity to produce AhR ligands also improved E. coli-induced mastitis in an AhR-dependent manner. These findings provide evidence for novel therapeutic strategies for treating mastitis, and support the role of metabolites derived from the intestinal microbiota in improving distal disease.