Intensive rice breeding over the past 50 y has dramatically increased productivity especially in the indica subspecies, but our knowledge of the genomic changes associated with such improvement has been limited. In this study, we analyzed low-coverage sequencing data of 1,479 rice accessions from 73 countries, including landraces and modern cultivars. We identified two major subpopulations, indica I (IndI) and indica II (IndII), in the indica subspecies, which corresponded to the two putative heterotic groups resulting from independent breeding efforts. We detected 200 regions spanning 7.8% of the rice genome that had been differentially selected between IndI and IndII, and thus referred to as breeding signatures. These regions included large numbers of known functional genes and loci associated with important agronomic traits revealed by genome-wide association studies. Grain yield was positively correlated with the number of breeding signatures in a variety, suggesting that the number of breeding signatures in a line may be useful for predicting agronomic potential and the selected loci may provide targets for rice improvement.) is one of the most important cereal crops in the world. There have been landmark achievements in rice improvement over the past 50 y, especially in the indica subspecies. A major breakthrough resulted from the independent development of a series of semidwarf varieties in China and by the International Rice Research Institute (IRRI) in the 1950s and 1960s, leading to the "green revolution" in rice. Since then, semidwarfness has been a basic characteristic for almost all modern varieties. Based on semidwarf varieties, improvement for other traits, such as abiotic stress resistance, broad-spectrum resistances to biotic stresses, and better grain quality, has also been achieved. Another major breakthrough stemmed from the exploitation of hybrid vigor in China (1), resulting in the largescale adoption of hybrid rice since the 1970s. Jointly, these breakthroughs have greatly increased rice productivity in the past several decades globally.Genomic studies in recent years have identified a large number of loci that were under selection during rice domestication (2). However, there has been very limited study to identify loci or genomic regions that have been under selection due to breeding. Next-generation sequencing technologies have enabled sequencing of a large number of rice accessions at relatively low cost, providing opportunities to inspect the genomic regions selected in the history of crop improvement. Meanwhile, genome-wide association studies (GWAS) have provided an effective approach to analyze the genetic architecture of complex traits and allow identification of candidate genes for further improvement of agronomically important traits (3,4).In this study, we analyzed low-coverage sequencing data of 1,479 rice accessions, which revealed a large number of differentially selected regions associated with breeding efforts between two major subpopulations in indica. These selected regi...

BackgroundAlthough an abundance of evidence has indicated that tumor-associated macrophages (TAMs) are associated with a favorable prognosis in patients with colon cancer, it is still unknown how TAMs exert a protective effect. This study examined whether TAMs are involved in hepatic metastasis of colon cancer.Materials and methodsOne hundred and sixty cases of pathologically-confirmed specimens were obtained from colon carcinoma patients with TNM stage IIIB and IV between January 1997 and July 2004 at the Cancer Center of Sun Yat-Sen University. The density of macrophages in the invasive front (CD68TFHotspot) was scored with an immunohistochemical assay. The relationship between the CD68TFHotspot and the clinicopathologic parameters, the potential of hepatic metastasis, and the 5-year survival rate were analyzed.ResultsTAMs were associated with the incidence of hepatic metastasis and the 5-year survival rate in patients with colon cancers. Both univariate and multivariate analyses revealed that the CD68TFHotspot was independently prognostic of survival. A higher 5-year survival rate among patients with stage IIIB after radical resection occurred in patients with a higher macrophage infiltration in the invasive front (81.0%) than in those with a lower macrophage infiltration (48.6%). Most importantly, the CD68TFHotspot was associated with both the potential of hepatic metastasis and the interval between colon resection and the occurrence of hepatic metastasis.ConclusionThis study showed evidence that TAMs infiltrated in the invasive front are associated with improvement in both hepatic metastasis and overall survival in colon cancer, implying that TAMs have protective potential in colon cancers and might serve as a novel therapeutic target.

BackgroundThe molecular mechanisms of the development and progression of bladder cancer are poorly understood. The objective of this study was to analyze the expression of Bmi-1 protein and its clinical significance in human bladder cancer.MethodsWe examined the expression of Bmi-1 mRNA and Bmi-1 protein by RT-PCR and Western blot, respectively in 14 paired bladder cancers and the adjacent normal tissues. The expression of Bmi-1 protein in 137 specimens of bladder cancer and 30 specimens of adjacent normal bladder tissue was determined by immunohistochemistry. Statistical analyses were applied to test the relationship between expression of Bmi-1, and clinicopathologic features and prognosis.ResultsExpression of Bmi-1 mRNA and protein was higher in bladder cancers than in the adjacent normal tissues in 14 paired samples (P < 0.01). By immunohistochemical examination, five of 30 adjacent normal bladder specimens (16.7%) versus 75 of 137 bladder cancers (54.3%) showed Bmi-1 protein expression (P < 0.05). Bmi-1 protein expression was intense in 20.6%, 54.3%, and 78.8% of tumors of histopathological stages G1, G2, and G3, respectively (P < 0.05). Expression of Bmi-1 protein was greater in invasive bladder cancers than in superficial bladder cancers (81.5% versus 32.5%, P < 0.05). In invasive bladder cancers, the expression of Bmi-1 protein in progression-free cancers was similar to that of cancers that have progressed (80.0% versus 82.4%, P > 0.5). In superficial bladder cancers, the expression of Bmi-1 protein in recurrent cases was higher than in recurrence-free cases (62.5% versus 13.7%, P < 0.05). Bmi-1 expression was positively correlated with tumor classification and TNM stage (P < 0.05), but not with tumor number (P > 0.05). Five-year survival in the group with higher Bmi-1 expression was 50.8%, while it was 78.5% in the group with lower Bmi-1 expression (P < 0.05). Patients with higher Bmi-1 expression had shorter survival time, whereas patients with lower Bmi-1 expression had longer survival time (P < 0.05).ConclusionExpression of Bmi-1 was greater in bladder cancers than in the adjacent normal tissues. The examination of Bmi-1 protein expression is potentially valuable in prognostic evaluation of bladder cancer.

BackgroundThe production of secondary metabolites with antibiotic properties is a common characteristic to entomopathogenic bacteria Xenorhabdus spp. These metabolites not only have diverse chemical structures but also have a wide range of bioactivities with medicinal and agricultural interests such as antibiotic, antimycotic and insecticidal, nematicidal and antiulcer, antineoplastic and antiviral. It has been known that cultivation parameters are critical to the secondary metabolites produced by microorganisms. Even small changes in the culture medium may not only impact the quantity of certain compounds but also the general metabolic profile of microorganisms. Manipulating nutritional or environmental factors can promote the biosynthesis of secondary metabolites and thus facilitate the discovery of new natural products. This work was conducted to evaluate the influence of nutrition on the antibiotic production of X. bovienii YL002 and to optimize the medium to maximize its antibiotic production.ResultsNutrition has high influence on the antibiotic production of X. bovienii YL002. Glycerol and soytone were identified as the best carbon and nitrogen sources that significantly affected the antibiotic production using one-factor-at-a-time approach. Response surface methodology (RSM) was applied to optimize the medium constituents (glycerol, soytone and minerals) for the antibiotic production of X. bovienii YL002. Higher antibiotic activity (337.5 U/mL) was obtained after optimization. The optimal levels of medium components were (g/L): glycerol 6.90, soytone 25.17, MgSO4·7H2O 1.57, (NH4)2SO4 2.55, KH2PO4 0.87, K2HPO4 1.11 and Na2SO4 1.81. An overall of 37.8% increase in the antibiotic activity of X. bovienii YL002 was obtained compared with that of the original medium.ConclusionsTo the best of our knowledge, there are no reports on antibiotic production of X. boviebii by medium optimization using RSM. The results strongly support the use of RSM for medium optimization. The optimized medium not only resulted in a 37.8% increase of antibiotic activity, but also reduced the numbers of experiments. The chosen method of medium optimization was efficient, simple and less time consuming. This work will be useful for the development of X. bovienii cultivation process for efficient antibiotic production on a large scale, and for the development of more advanced control strategies on plant diseases.

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