Colorectal cancer-associated fibroblasts promote metastasis by up-regulating LRG1 through stromal IL-6/STAT3 signaling

Cancer-associated fibroblasts (CAFs) have been shown to play a strong role in colorectal cancer metastasis, yet the underlying mechanism remains to be fully elucidated. Using CRC clinical samples together with ex vivo CAFs-CRC co-culture models, we found that CAFs induce expression of Leucine Rich Alpha-2-Glycoprotein 1(LRG1) in CRC, where it shows markedly higher expression in metastatic CRC tissues compared to primary tumors. We further show that CAFs-induced LRG1 promotes CRC migration and invasion that is concomitant with EMT (epithelial-mesenchymal transition) induction. In addition, this signaling axis has also been confirmed in the liver metastatic mouse model which displayed CAFs-induced LRG1 substantially accelerates metastasis. Mechanistically, we demonstrate that CAFs-secreted IL-6 (interleukin-6) is responsible for LRG1 up-regulation in CRC, which occurs through a direct transactivation by STAT3 following JAK2 activation. In clinical CRC tumor samples, LRG1 expression was positively correlated with CAFs-specific marker, α-SMA, and a higher LRG1 expression predicted poor clinical outcomes especially distant metastasis free survival, supporting the role of LRG1 in CRC progression. Collectively, this study provided a novel insight into CAFs-mediated metastasis in CRC and indicated that therapeutic targeting of CAFs-mediated IL-6-STAT3-LRG1 axis might be a potential strategy to mitigate metastasis in CRC.Subject terms: Colon cancer, Cancer microenvironment     

Functional roles of PC‐PLC and Cdc20 in the cell cycle,proliferation, and apoptosis

Phosphatidylcholine‐specific phospholipase C (PC‐PLC) is the major enzyme in the Phosphatidylcholine (PC) cycle and is involved in many long‐term cellular responses such as activation, proliferation, and differentiation events. Cell division cycle 20 homolog (Cdc20) is an essential cell‐cycle regulator required for the completion of mitosis. Our previous studies identified the interaction between PC‐PLC and Cdc20. Through the interaction, Cdc20 could mediate the degradation of PC‐PLC by Cdc20‐mediated ubiquitin proteasome pathway (UPP). In this study, we found that PC‐PLC might not be involved in cancer metastasis. Inhibition of PC‐PLC by D609 could cause cell proliferation inhibition and apoptosis inhibition in CBRH‐7919 cells. Inhibition of PC‐PLC could also influence the cell cycle by arresting the cells in G1 phase, and Cdc20 might be involved in these processes. Taken together, in this report, we provided new evidence for the functional roles of PC‐PLC and Cdc20 in the cell cycle, proliferation, and apoptosis in CBRH‐7919 cells. Copyright © 2010 John Wiley & Sons, Ltd.     

Contrasting effects of clipping and nutrient addition on reproductive traits of Heteropappus altaicus at the individual and population levels

This study was conducted to examine the effects of clipping and nutrient addition on plant traits of a dominant perennial forb species, Heteropappus altaicus (Willd.) Novopokr. (Compositae), at both the individual and population levels in a temperate steppe in northern China. A nested experimental design was used with clipping as the main factor and nutrient, including nitrogen (N), phosphorus (P) and both, addition as the second factor. The main effect of clipping reduced plant height, aboveground biomass (AGB) per plant, and pollen production per floret by 15.8, 34.3, 28.0% (all p < 0.05), respectively, but enhanced reproductive allocation and population density by 8 and 28.2% (both p < 0.05), respectively, suggesting contrary effects of clipping on H. altaicus traits at the individual and population levels. N addition significantly stimulated plant height, AGB per plant, reproductive allocation, pollen diameter, and pistil length, but decreased population density. The main effects of P addition also stimulated the plant traits at individual level, but did not change population traits. The significant interactions of clipping and nitrogen addition were observed on AGB per plant, pollen production, and population density. The differential responses of H. altaicus at the individual and population levels to clipping and nutrient addition indicate that the future dynamics of H. altaicus in the temperate steppe are uncertain and need long-term research to demonstrate.     

Phylogeography of the Common Pheasant Phasianus colchicus

The Common Pheasant Phasianus colchicus is widely distributed in temperate to subtropical regions of the Palaearctic realm. Populations of Common Pheasant have been classified into five subspecies groups based on morphological variations in male plumage. Previous phylogeographical studies have focused on limited sets of subspecies groups in the eastern Palaearctic and knowledge on subspecies in the western Palaearctic region is still poor. In this study, we undertake the first comprehensive analysis of subspecies from all five defined subspecies groups across the entire Palaearctic region. Two mitochondrial (CYTB and CR) and two nuclear (HMG and SPI) loci were used to investigate genetic relationships of these subspecies groups and to infer their dispersal routes. Our results revealed that the subspecies elegans, with its range in northwestern Yunnan, China, was in the basal position among 17 studied subspecies, supporting a previous hypothesis that the Common Pheasant most probably originated in forests in southeastern China. Subspecies in the western Palaearctic region nested within the most subspecies‐rich torquatus group (‘Grey‐rumped Pheasants’), indicating that the torquatus group is not a clade but instead forms a gradation with other subspecies and subspecies groups. Our dating analysis suggested that the initial divergence among populations of Common Pheasant originated around 3.4 Mya with subsequent dispersal into the Western Palaearctic region during the Late Pliocene–Lower Pleistocene approximately 2.5–1.8 Mya. We propose two possible east‐to‐west colonization routes for the Common Pheasant and suggest conservation implications for some regional subspecies. Overall, this study demonstrates the lack of concordance between morphology‐based subspecies delimitation and their genetic relationships. This is likely to be a consequence of initial isolation due to historical vicariance followed by population admixture due to recent range expansion of Common Pheasant in the western Palaearctic region.     

Field Studies of the Wheat Stomata Resistance Influenced by Soil Water Content

Concurrent observations of soil water potential and leaf stomata diffusion resistance were made on two, plots of wheat grown at Datun Agro-ecological Experimental Station in Beijing under two different soil water conditions. These data were further complemented by weather and physiological observation. In this paper, we mainly analysed the influence of soil water potential on the status of wheat leaf stomatal resistance. The results indicate that: (1) there is a obvious influence of soil water potential on the status of wheat leaf stomata under normal conditions and (2) there is a different upper and lower epidermis stomata of wheat leaf respond to the soil water potential. The lower epidermis stomata are more sensitive to soil water potential than upper epidermis one. (3) There is a linear relationship between the ratio of lower and upper epidermis stomata resistance and soil water potential in root layer, according to this we can diagnose the degree of wheat water deficit.     

Regulation of progesterone during follicular development by FSH and LH in sheep

Progesterone (P4) can participate in the development of female mammalian antral follicles through nuclear receptor (PGR). In this experiment, the differences of P4 synthesis and PGR expression in different developmental stages of sheep antral follicles (large > 5mm, medium 2-5mm, small < 2mm) were detected by enzyme-linked immunosorbent assay, immunohistochemistry, qRT-PCR and Western blotting. Secondly, sheep follicular granulosa cells were cultured in vitro. The effects of different concentrations of FSH and LH on P4 synthesis and PGR expression were studied. The results showed that acute steroid regulatory protein (StAR), cholesterol side chain lyase (P450scc) and 3β Hydroxysteroid dehydrogenase (3β-HSD) and PGR were expressed in antral follicles, and with the development of antral follicles in sheep, StAR, P450scc and the expression of 3β-HSD and PGR increased significantly. In vitro experiments showed that FSH and LH alone or together treatment could regulate P4 secretion and PGR expression in sheep follicular granulosa cells to varying degrees, hint P4 and PGR by FSH and LH, and LH was the main factor. Our results supplement the effects of FSH and LH on the regulation of P4 synthesis during follicular development, which provides new data for further study of steroid synthesis and function in follicular development.     

The Bryopsis hypnoides plastid genome: multimeric forms and complete nucleotide sequence

Background

Bryopsis hypnoides Lamouroux is a siphonous green alga, and its extruded protoplasm can aggregate spontaneously in seawater and develop into mature individuals. The chloroplast of B. hypnoides is the biggest organelle in the cell and shows strong autonomy. To better understand this organelle, we sequenced and analyzed the chloroplast genome of this green alga.

Principal Findings

A total of 111 functional genes, including 69 potential protein-coding genes, 5 ribosomal RNA genes, and 37 tRNA genes were identified. The genome size (153,429 bp), arrangement, and inverted-repeat (IR)-lacking structure of the B. hypnoides chloroplast DNA (cpDNA) closely resembles that of Chlorella vulgaris. Furthermore, our cytogenomic investigations using pulsed-field gel electrophoresis (PFGE) and southern blotting methods showed that the B. hypnoides cpDNA had multimeric forms, including monomer, dimer, trimer, tetramer, and even higher multimers, which is similar to the higher order organization observed previously for higher plant cpDNA. The relative amounts of the four multimeric cpDNA forms were estimated to be about 1, 1/2, 1/4, and 1/8 based on molecular hybridization analysis. Phylogenetic analyses based on a concatenated alignment of chloroplast protein sequences suggested that B. hypnoides is sister to all Chlorophyceae and this placement received moderate support.

Conclusion

All of the results suggest that the autonomy of the chloroplasts of B. hypnoides has little to do with the size and gene content of the cpDNA, and the IR-lacking structure of the chloroplasts indirectly demonstrated that the multimeric molecules might result from the random cleavage and fusion of replication intermediates instead of recombinational events.     

Plant nitrogen dynamics and nitrogen-use strategies under altered nitrogen seasonality and competition

BACKGROUND AND AIMS: Numerous studies have examined the effects of climatic factors on the distribution of C(3) and C(4) grasses in various regions throughout the world, but the role of seasonal fluctuations in temperature, precipitation and soil N availability in regulating growth and competition of these two functional types is still not well understood. This report is about the effects of seasonality of soil N availability and competition on plant N dynamics and N-use strategies of one C(3) (Leymus chinensis) and one C(4) (Chloris virgata) grass species. METHODS: Leymus chinensis and C. virgata, two grass species native to the temperate steppe in northern China, were planted in a monoculture and a mixture under three different N seasonal availabilities: an average model (AM) with N evenly distributed over the growing season; a one-peak model (OM) with more N in summer than in spring and autumn; and a two-peak model (TM) with more N in spring and autumn than in summer. KEY RESULTS: The results showed that the altered N seasonality changed plant N concentration, with the highest value of L. chinensis under the OM treatment and C. virgata under the TM treatment, respectively. N seasonality also affected plant N content, N productivity and N-resorption efficiency and proficiency in both the C(3) and C(4) species. Interspecific competition influenced N-use and resorption efficiency in both the C(3) and C(4) species, with higher N-use and resorption efficiency in the mixture than in monoculture. The C(4) grass had higher N-use efficiency than the C(3) grass due to its higher N productivity, irrespective of the N treatment or competition. CONCLUSIONS: The observations suggest that N-use strategies in the C(3) and C(4) species used in the study were closely related to seasonal dynamics of N supply and competition. N seasonality might be involved in the growth and temporal niche separation between C(3) and C(4) species observed in the natural ecosystems.