Fusarium head blight (FHB), a fungal disease caused by Fusarium species that produce food toxins, currently devastates wheat production worldwide, yet few resistance resources have been discovered in wheat germplasm. Here, we cloned the FHB resistance gene Fhb7 by assembling the genome of Thinopyrum elongatum, a species used in wheat distant hybridization breeding. Fhb7 encodes a glutathione S-transferase (GST) and confers broad resistance to Fusarium species by detoxifying trichothecenes through de-epoxidation. Fhb7 GST homologs are absent in plants, and our evidence supports that Th. elongatum has gained Fhb7 through horizontal gene transfer (HGT) from an endophytic Epichloë species. Fhb7 introgressions in wheat confers resistance to both FHB and crown rot in diverse wheat backgrounds without yield penalty, providing a solution for Fusarium resistance breeding.
Introduction. The occurrence of malignant disease increases the risk for venous thromboembolism (VTE). Here we evaluate the risk for VTE in a large unselected cohort of patients with cancer receiving chemotherapy. Methods. The United States IMPACT health care claims database was retrospectively analyzed to identify patients with a range of solid tumors who started chemotherapy from January 2005 through December 2008. International Classification of Diseases, 9th revision, Clinical Modification Codes were used to identify cancer location, presence of VTE 3.5 months and 12 months after starting chemotherapy, and incidence of major bleeding complications. Health care costs were assessed one year before initiation of chemotherapy and one year after initiation of chemotherapy.Results. The overall incidence of VTE 3.5 months after starting chemotherapy was 7.3% (range 4.6%-11.6% across cancer locations) rising to 13.5% at 12 months (range 9.8%-21.3%). The highest VTE risk was identified in patients with pancreatic, stomach, and lung cancer. Patients in whom VTE developed had a higher risk for major bleeding at 3.5 months and at 12 months (11.0% and 19.8% vs. 3.8% and 9.6%, respectively). Health care costs were significantly higher in patients in whom VTE developed. Conclusion. Those undergoing chemotherapy as outpatients are at increased risk for VTE and for major bleeding complications. Thromboprophylaxis may be considered for such patients after carefully assessing the risks and benefits of treatment. The Oncologist 2013;18:1321-1329 Implications for Practice: This large observational study of unselected patients receiving cancer chemotherapy demonstrates considerably greater rates of venous thromboembolism (VTE) than commonly reported in patients accrued to clinical trials. The risk of VTE appears to increase progressively over the year following initiation of treatment. Cancer patients developing VTE also experience a greater risk of major bleeding and greater health care costs than patients without VTE. Patients considered at high risk for VTE should be considered for thromboprophylaxis after assessing the balance of potential benefits and harms.
Cathaya argyrophylla is an endangered conifer restricted to subtropical mountains of China. To study phylogeographical pattern and demographic history of C. argyrophylla, species-wide genetic variation was investigated using sequences of maternally inherited mtDNA and biparentally inherited nuclear DNA. Of 15 populations sampled from all four distinct regions, only three mitotypes were detected at two loci, without single region having a mixed composition (G(ST) = 1). Average nucleotide diversity (theta(ws) = 0.0024; pi(s) = 0.0029) across eight nuclear loci is significantly lower than those found for other conifers (theta(ws) = 0.003 approximately 0.015; pi(s) = 0.002 approximately 0.012) based on estimates of multiple loci. Because of its highest diversity among the eight nuclear loci and evolving neutrally, one locus (2009) was further used for phylogeographical studies and eight haplotypes resulting from 12 polymorphic sites were obtained from 98 individuals. All the four distinct regions had at least four haplotypes, with the Dalou region (DL) having the highest diversity and the Bamian region (BM) the lowest, paralleling the result of the eight nuclear loci. An AMOVA revealed significant proportion of diversity attributable to differences among regions (13.4%) and among populations within regions (8.9%). F(ST) analysis also indicated significantly high differentiation among populations (F(ST) = 0.22) and between regions (F(ST) = 0.12-0.38). Non-overlapping distribution of mitotypes and high genetic differentiation among the distinct geographical groups suggest the existence of at least four separate glacial refugia. Based on network and mismatch distribution analyses, we do not find evidence of long distance dispersal and population expansion in C. argyrophylla. Ex situ conservation and artificial crossing are recommended for the management of this endangered species.
BackgroundThe proliferation of retinal pigment epithelium (RPE) cells resulting from an epithelial-mesenchymal transition (EMT) plays a key role in proliferative vitreoretinopathy (PVR), which leads to complex retinal detachment and the loss of vision. Genes of Snail family encode the zinc finger transcription factors that have been reported to be essential in EMT during embryonic development and cancer metastasis. However, the function of Snail in RPE cells undergoing EMT is largely unknown.Principal FindingsTransforming growth factor beta(TGF-β)-1 resulted in EMT in human RPE cells (ARPE-19), which was characterized by the expected decrease in E-cadherin and Zona occludin-1(ZO-1) expression, and the increase in fibronectin and α-smooth muscle actin (α-SMA) expression, as well as the associated increase of Snail expression at both mRNA and protein levels. Furthermore, TGF-β1 treatment caused a significant change in ARPE-19 cells morphology, with transition from a typical epithelial morphology to mesenchymal spindle-shaped. More interestingly, Snail silencing significantly attenuated TGF-β1-induced EMT in ARPE-19 cells by decreasing the mesenchymal markers fibronectin and a-SMA and increasing the epithelial marker E-cadherin and ZO-1. Snail knockdown could effectively suppress ARPE-19 cell migration. Finally, Snail was activated in epiretinal membranes from PVR patients. Taken together, Snail plays very important roles in TGF-β-1-induced EMT in human RPE cells and may contribute to the development of PVR.SignificanceSnail transcription factor plays a critical role in TGF-β1-induced EMT in human RPE cells, which provides deep insight into the pathogenesis of human PVR disease. The specific inhibition of Snail may provide a new approach to treat and prevent PVR.
Purpose: We examined the presence of the pregnane X receptor (PXR) and its effects on ovarian cancer cells after activation by its cognate ligand. Experimental Design: SKOV-3 and OVCAR-8 ovarian carcinoma cells were analyzed for expression of PXR by quantitative reverse transcription-PCR and Western blot. Human ovarian cancer tissue was also analyzed for PXR expression by immunochemistry. Ligand (agonist)î nduced PXR target genes were analyzed in SKOV-3 cells by quantitative reverse transcription-PCR. SKOV-3 cell proliferation was assessed by MTTassay. In vivo confirmation of in vitro effects of PXR ligands were done in NOD.SCID mice carrying SKOV-3 xenografts.
Ginseng root is used more often than other parts such as leaf stem although extracts from ginseng leaf-stem also contain similar active ingredients with pharmacological functions. Ginseng's leaf-stems are more readily available at a lower cost than its root. This article reviews the pharmacological effects of ginseng leaf-stem on some diseases and adverse effects due to excessive consumption. Ginseng leaf-stem extract contains numerous active ingredients, such as ginsenosides, polysaccharides, triterpenoids, flavonoids, volatile oils, polyacetylenic alcohols, peptides, amino acids and fatty acids. The extract contains larger amounts of the same active ingredients than the root. These active ingredients produce multifaceted pharmacological effects on the central nervous system, as well as on the cardiovascular, reproductive and metabolic systems. Ginseng leaf-stem extract also has anti-fatigue, anti-hyperglycemic, anti-obesity, anti-cancer, anti-oxidant and anti-aging properties. In normal use, ginseng leaf-stem extract is quite safe; adverse effects occur only when it is over dosed or is of poor quality. Extracts from ginseng root and leaf-stem have similar multifaceted pharmacological activities (for example central nervous and cardiovascular systems). In terms of costs and source availability, however, ginseng leaf-stem has advantages over its root. Further research will facilitate a wider use of ginseng leaf-stem.
Objective: Our aim was to validate the prognostic relevance in NSCLC of potential residual tumor (R) descriptors, including the proposed International Association for the Study of Lung Cancer definition for uncertain resection, referred to as R(un).Methods: A total of 14,712 patients undergoing resection with full R status and survival were analyzed. The following were also evaluated: whether fewer than three N2 stations
We have examined the clinical characteristics and treatment of ectopic meningiomas (EMs). Samples from 17 patients with EMs were analyzed, and their clinical characteristics, mechanism, and treatment were studied in combination with the literature. The main clinical manifestations of EMs included increased intracranial pressure, epilepsy, local mass, and local occupying effects, but diagnosis of EMs depended on the pathology. Surgical removal can achieve the double objectives of confirmed diagnosis and treatment of tumors. The clinical characteristics of EMs vary with the sites of tumors. Operation is the treatment of first choice. Prognosis is better than that of typical meningiomas.
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