Intensive expression of Bmi-1 is a new independent predictor of poor outcome in patients with ovarian carcinoma

Background: It has been suggested that the B-cell specific moloney leukemia virus insertion site 1 (Bmi-1) gene plays an oncogenic role in several types of human cancer, but the status of Bmi-1 amplification and expression in ovarian cancer and its clinical/prognostic significance are unclear.Methods: The methods of immunohistochemistry and fluorescence in situ hybridization were utilized to examine protein expression and amplification of Bmi-1 in 30 normal ovaries, 30 ovarian cystadenomas, 40 borderline ovarian tumors and 179 ovarian carcinomas.Results: Intensive expression of Bmi-1 was detected in none of the normal ovaries, 3% cystadenomas, 10% borderline tumors, and 37% ovarian carcinomas, respectively. Amplification of Bmi-1 was detected in 8% of ovarian carcinomas. In ovarian carcinomas, significant positive associations were found between intensive expression of Bmi-1 and the tumors ascending histological grade, later pT/pN/pM and FIGO stages (P < 0.05). In univariate survival analysis of the ovarian carcinoma cohorts, a significant association of intensive expression of Bmi-1 with shortened patient survival (mean 49.3 months versus 100.3 months, p < 0.001) was demonstrated. Importantly, Bmi-1 expression provided significant independent prognostic parameters in multivariate analysis (p = 0.005).Conclusions: These findings provide evidence that intensive expression of Bmi-1 might be important in the acquisition of an invasive and/or aggressive phenotype of ovarian carcinoma, and serve as a independent biomarker for shortened survival time of patients. © 2010 Yang et al; licensee BioMed Central Ltd.published_or_final_versio

Post-impoundment biomass and composition of phytoplankton in the Yangtze River

Damming, and thus alteration of stream flow, promotes higher phytoplankton populations and encourages algal blooms (density &gt; 10(6) cells L-1) in the Three Gorges Reservoir (TGR). Phytoplankton composition and biomass were studied in the Yangtze River from March 2004 to May 2005. 107 taxa were identified. Diatoms were the dominant group, followed by Chlorophyta and Cyanobacteria. In the Yangtze River, algal abundance varied from 3.13 x 10(3) to 3.83 x 10(6) cells L-1, and algal biomass was in the range of 0.06 to 659 mg C m(-3). Levels of nitrogen, phosphorus and silica did not show consistent longitudinal changes along the river and were not correlated with phytoplankton parameters. Phytoplankton abundance was negatively correlated with main channel discharge (Spearman r = -1.000, P &lt; 0.01). Phytoplankton abundance and biomass in the Yangtze River are mainly determined by the hydrological conditions rather than by nutrient concentrations.Damming, and thus alteration of stream flow, promotes higher phytoplankton populations and encourages algal blooms (density > 10(6) cells L-1) in the Three Gorges Reservoir (TGR). Phytoplankton composition and biomass were studied in the Yangtze River from March 2004 to May 2005. 107 taxa were identified. Diatoms were the dominant group, followed by Chlorophyta and Cyanobacteria. In the Yangtze River, algal abundance varied from 3.13 x 10(3) to 3.83 x 10(6) cells L-1, and algal biomass was in the range of 0.06 to 659 mg C m(-3). Levels of nitrogen, phosphorus and silica did not show consistent longitudinal changes along the river and were not correlated with phytoplankton parameters. Phytoplankton abundance was negatively correlated with main channel discharge (Spearman r = -1.000, P < 0.01). Phytoplankton abundance and biomass in the Yangtze River are mainly determined by the hydrological conditions rather than by nutrient concentrations

The Effects of Carbon Dioxide Removal on the Carbon Cycle

Increasing atmospheric CO2 is having detrimental effects on the Earth system. Societies have recognized that anthropogenic CO2 release must be rapidly reduced to avoid potentially catastrophic impacts. Achieving this via emissions reductions alone will be very difficult. Carbon dioxide removal (CDR) has been suggested to complement and compensate for insufficient emissions reductions, through increasing natural carbon sinks, engineering new carbon sinks, or combining natural uptake with engineered storage. Here, we review the carbon cycle responses to different CDR approaches and highlight the often-overlooked interaction and feedbacks between carbon reservoirs that ultimately determines CDR efficacy. We also identify future research that will be needed if CDR is to play a role in climate change mitigation, these include coordinated studies to better understand (i) the underlying mechanisms of each method, (ii) how they could be explicitly simulated, (iii) how reversible changes in the climate and carbon cycle are, and (iv) how to evaluate and monitor CDR

Mapping quantitative trait loci in line cross with repeat records

<p>Abstract</p> <p>Background</p> <p>Phenotypes with repeat records from one individual or multiple individuals were often encountered in practices of mapping QTL in linecross. The current genetic mapping method for a trait with repeat records is adopted by simply replacing the phenotype by the average value of the repeat records. This simple treatment has not sufficiently utilized the information from the replication and ignored the impacts of the permanent environmental effects on the accuracy of the estimated QTL.</p> <p>Results</p> <p>We propose to map QTL by using the repeatability model to directly analyze the repeat records rather than simply analyze the mean phenotype, improving the efficiency of QTL detecting because of adequately utilizing the information from data and allowing for the permanent environmental effects. A maximum likelihood method implemented via the expectation-maximization (EM) algorithm is applied to perform the parameter estimation of the repeatability model. The superiority of the mapping method based on the repeatability model over simple analysis using the mean phenotype was demonstrated by a series of simulations.</p> <p>Conclusion</p> <p>Our results suggest that the proposed method can serve as a powerful alternative to existing methods. By mean of the repeatability model, utilizing the repeat records on individual may improve the efficiency of QTL detecting in line cross.</p

How much can we gain from improved efficiency? An examination of performance of national HIV/AIDS programs and its determinants in low- and middle-income countries

<p>Abstract</p> <p>Background</p> <p>The economic downturn exacerbates the inadequacy of resources for combating the worldwide HIV/AIDS pandemic and amplifies the need to improve the efficiency of HIV/AIDS programs.</p> <p>Methods</p> <p>We used data envelopment analysis (DEA) to evaluate efficiency of national HIV/AIDS programs in transforming funding into services and implemented a Tobit model to identify determinants of the efficiency in 68 low- and middle-income countries. We considered the change from the lowest quartile to the average value of a variable a "notable" increase.</p> <p>Results</p> <p>Overall, the average efficiency in implementing HIV/AIDS programs was moderate (49.8%). Program efficiency varied enormously among countries with means by quartile of efficiency of 13.0%, 36.4%, 54.4% and 96.5%. A country's governance, financing mechanisms, and economic and demographic characteristics influence the program efficiency. For example, if countries achieved a notable increase in "voice and accountability" (e.g., greater participation of civil society in policy making), the efficiency of their HIV/AIDS programs would increase by 40.8%. For countries in the lowest quartile of per capita gross national income (GNI), a notable increase in per capita GNI would increase the efficiency of AIDS programs by 45.0%.</p> <p>Conclusions</p> <p>There may be substantial opportunity for improving the efficiency of AIDS services, by providing more services with existing resources. Actions beyond the health sector could be important factors affecting HIV/AIDS service delivery.</p

Altered Germination and Subcellular Localization Patterns for PUB44/SAUL1 in Response to Stress and Phytohormone Treatments

BACKGROUND: In plants, the ubiquitin-proteasome system is emerging as a significant regulatory system throughout the plant lifecycle. The ubiquitination of a target protein requires the sequential actions of the E1, E2 and E3 enzymes, with the latter E3 enzyme conferring target selection in this process. There are a large number of predicted E3 enzymes in plant genomes, and very little is known about the functions of many of these predicted genes. Here we report here an analysis of two closely-related members of the Arabidopsis Plant U-box (PUB) family of E3 ubiquitin ligases, PUB43 and PUB44. PRINCIPAL FINDINGS: Homozygous pub44/pub44 mutant seedlings were found displayed a seedling lethal phenotype and this corresponded with widespread cell death lesions throughout the cotyledons and roots. Interestingly, heterozygous PUB44/pub44 seedlings were wild-type in appearance yet displayed intermediate levels of cell death lesions in comparison to pub44/pub44 seedlings. In contrast, homozygous pub43/pub43 mutants were viable and did not show any signs of cell death despite the PUB43 gene being more highly expressed than PUB44. The PUB44 mutants are not classical lesion mimic mutants as they did not have increased resistance to plant pathogens. We also observed increased germination rates in mutant seeds for both PUB44 and PUB43 under inhibitory concentrations of abscisic acid. Finally, the subcellular localization of PUB44 was investigated with transient expression assays in BY-2 cells. Under varying conditions, PUB44 was observed to be localized to the cytoplasm, plasma membrane, or nucleus. CONCLUSIONS: Based on mutant plant analyses, the Arabidopsis PUB43 and PUB44 genes are proposed to function during seed germination and early seedling growth. Given PUB44's ability to shuttle from the nucleus to the plasma membrane, PUB44 may be active in different subcellular compartments as part of these biological functions

In vitro and in vivo activity and cross resistance profiles of novel ruthenium (II) organometallic arene complexes in human ovarian cancer.

Ruthenium complexes offer the potential of reduced toxicity, a novel mechanism of action, non-cross resistance and a different spectrum of activity compared to platinum containing compounds. Thirteen novel ruthenium(II) organometallic arene complexes have been evaluated for activity (in vitro and in vivo) in models of human ovarian cancer, and cross-resistance profiles established in cisplatin and multi-drug-resistant variants. A broad range of IC50 values was obtained (0.5 to >100 microM) in A2780 parental cells with two compounds (RM175 and HC29) equipotent to carboplatin (6 microM), and the most active compound (HC11) equipotent to cisplatin (0.6 microM). Stable bi-dentate chelating ligands (ethylenediamine), a more hydrophobic arene ligand (tetrahydroanthracene) and a single ligand exchange centre (chloride) were associated with increased activity. None of the six active ruthenium(II) compounds were cross-resistant in the A2780cis cell line, demonstrated to be 10-fold resistant to cisplatin/carboplatin by a mechanism involving, at least in part, silencing of MLH1 protein expression via methylation. Varying degrees of cross-resistance were observed in the P-170 glycoprotein overexpressing multi-drug-resistant cell line 2780AD that could be reversed by co-treatment with verapamil. In vivo activity was established with RM175 in the A2780 xenograft together with non-cross-resistance in the A2780cis xenograft and a lack of activity in the 2780AD xenograft. High activity coupled to non cross-resistance in cisplatin resistant models merit further development of this novel group of anticancer compounds

Cdk5 Is Required for Memory Function and Hippocampal Plasticity via the cAMP Signaling Pathway

Memory formation is modulated by pre- and post-synaptic signaling events in neurons. The neuronal protein kinase Cyclin-Dependent Kinase 5 (Cdk5) phosphorylates a variety of synaptic substrates and is implicated in memory formation. It has also been shown to play a role in homeostatic regulation of synaptic plasticity in cultured neurons. Surprisingly, we found that Cdk5 loss of function in hippocampal circuits results in severe impairments in memory formation and retrieval. Moreover, Cdk5 loss of function in the hippocampus disrupts cAMP signaling due to an aberrant increase in phosphodiesterase (PDE) proteins. Dysregulation of cAMP is associated with defective CREB phosphorylation and disrupted composition of synaptic proteins in Cdk5-deficient mice. Rolipram, a PDE4 inhibitor that prevents cAMP depletion, restores synaptic plasticity and memory formation in Cdk5-deficient mice. Collectively, our results demonstrate a critical role for Cdk5 in the regulation of cAMP-mediated hippocampal functions essential for synaptic plasticity and memory formation.Norman B. Leventhal FellowshipUnited States. National Institutes of Health (NIH T32 MH074249)United States. National Institutes of Health (NIH RO1 NS051874

PPARδ Activation Acts Cooperatively with 3-Phosphoinositide-Dependent Protein Kinase-1 to Enhance Mammary Tumorigenesis

Peroxisome proliferator-activated receptorδ (PPARδ) is a transcription factor that is associated with metabolic gene regulation and inflammation. It has been implicated in tumor promotion and in the regulation of 3-phosphoinositide-dependent kinase-1 (PDK1). PDK1 is a key regulator of the AGC protein kinase family, which includes the proto-oncogene AKT/PKB implicated in several malignancies, including breast cancer. To assess the role of PDK1 in mammary tumorigenesis and its interaction with PPARδ, transgenic mice were generated in which PDK1 was expressed in mammary epithelium under the control of the MMTV enhancer/promoter region. Transgene expression increased pT308AKT and pS9GSK3β, but did not alter phosphorylation of mTOR, 4EBP1, ribosomal protein S6 and PKCα. The transgenic mammary gland also expressed higher levels of PPARδ and a gene expression profile resembling wild-type mice maintained on a diet containing the PPARδ agonist, GW501516. Both wild-type and transgenic mice treated with GW501516 exhibited accelerated rates of tumor formation that were more pronounced in transgenic animals. GW501516 treatment was accompanied by a distinct metabolic gene expression and metabolomic signature that was not present in untreated animals. GW501516-treated transgenic mice expressed higher levels of fatty acid and phospholipid metabolites than treated wild-type mice, suggesting the involvement of PDK1 in enhancing PPARδ-driven energy metabolism. These results reveal that PPARδ activation elicits a distinct metabolic and metabolomic profile in tumors that is in part related to PDK1 and AKT signaling