The subtype-specific molecular function of SPDEF in breast cancer and insights into prognostic significance

Breast cancer (BC) is a molecular diverse disease which becomes the most common malignancy among women worldwide. There are four BC subtypes (Luminal A, Luminal B, HER2-enriched and Basal-like) robustly established following gene expression pattern-based characterization, behave significant differences in terms of their incidence, risk factors, prognosis and therapeutic sensitivity. Thus, there is an urgent need to provide mechanism research, treatment strategies and/or prognosis evaluation based on the patient stratification of BC subtypes. The prostate-derived ETS factor SPDEF was first identified as an activator of prostate specific antigen, and then, the involvements in many aspects of BC have been proposed. However, the subtype-specific molecular function of SPDEF in BC and insights into prognostic significance have not been clearly elucidated. This study demonstrated for the first time that SPDEF may play a diversity role in the expression levels, clinicopathologic importance, biological function and prognostic evaluation in BC via bioinformatics and experimental evidence, which mainly depends on different BC subtyping. In summary, our findings would help to better understand the possible mechanisms of various BC subtypes and to find possible candidate genes for prognostic and therapeutic usage.     

Host-Polarized Cell Growth in Animal Symbionts

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Life cycle assessment of copper production: a case study in China

Purpose

China is the world’s largest producer and consumer of refined and reclaimed copper because of the rapid economic and industrial development of this country. However, only a few studies have analyzed the environmental impact of China’s copper industry. The current study analyzes the life cycle environmental impact of copper production in China.

Methods

A life cycle impact assessment using the ReCiPe method was conducted to estimate the environmental impact of refined and reclaimed copper production in China. Uncertainty analysis was also performed based on the Monte-Carlo simulation.

Results and discussion

The environmental impact of refined copper was higher than that of reclaimed copper in almost all categories except for human toxicity because of the direct atmospheric arsenic emission during the copper recycling stage. The overall environmental impact for the refined copper production was mainly attributed to metal depletion, freshwater ecotoxicity, marine ecotoxicity, and water depletion potential impact. By contrast, that for the reclaimed copper production was mainly caused by human toxicity impact.

Conclusions

Results show that the reclaimed copper scenario had approximately 59 to 99% more environmental benefits than those of the refined copper scenario in most key categories except for human toxicity, in which a similar environmental burden was observed between both scenarios. The key factors that reduce the overall environmental impact for China’s copper industry include decreasing direct heavy metal emissions in air and water, increasing the national recycling rate of copper, improving electricity consumption efficiency, replacing coal with clean energy sources for electricity production, and optimizing the efficiency of copper ore mining and consumption.

     

Ecological risk assessment of polycyclic aromatic hydrocarbons in surface sediments from the middle and lower reaches of the Yellow River,China

In this research, ecological risks for eight individual polycyclic aromatic hydrocarbons (PAHs) and ∑PAH₈ in surface sediments from middle and lower reaches of Yellow River are evaluated using overlapping areas of probability density curves and margin of safety (MOS), based on the toxicity data and the exposure concentrations of PAHs in sediments collected from 23 sites. In the overlapping areas of probability density curves, the risk of Ant and Pyr are the highest, then the risk level is in the order of Flua > Nap > Phe > BaP > Flu > Ace. The values of MOS₁₀ present that Pyr (4.62 × 10^?4), Ant (5.60 × 10^?3), and Flua (6.4 × 10^?3) have a significantly high ecological risk level, while Nap and Phe have middle-level ecological risk. As for Ace, BaP, and Flu, they pose limited risk to the ecological system with MOS₁₀ greater than 1.0. The ∑PAH₈ (2.66 × 10^?5) is a higher risk level than that of any individual PAHs, where the probabilities of ∑PAH₈ in excess of the 10th percentile of the toxicity data were 86%.     

Acetylation of Smc3 by Eco1 is required for S phase sister chromatid cohesion in both human and yeast

Sister chromatid cohesion is normally established in S phase in a process that depends on the cohesion establishment factor Eco1, a conserved acetyltransferase. However, due to the lack of known in vivo substrates, how Eco1 regulates cohesion is not understood. Here we report that yeast Eco1 and its human ortholog, ESCO1, both acetylate Smc3, a component of the cohesin complex that physically holds the sister chromatid together, at two conserved lysine residues. Mutating these lysine residues to a nonacetylatable form leads to increased loss of sister chromatid cohesion and genome instability in both yeast and human. In addition, we clarified that the acetyltransferase activity of Eco1 is essential for its function. Our study thus identified a molecular target for the acetyltransferase Eco1 and revealed that Smc3 acetylation is a conserved mechanism in regulating sister chromatid cohesion.     

Regulation of intra-S phase checkpoint by ionizing radiation (IR)-dependent and IR-independent phosphorylation of SMC3

Structure maintenance of chromosome 1 (SMC1) is phosphorylated by ataxia telangiectasia-mutated (ATM) in response to ionizing radiation (IR) to activate intra-S phase checkpoint. A role of CK2 in DNA damage response has been implicated in many previous works, but the molecular mechanism for its activation is not clear. In the present work, we report that SMC3 is phosphorylated at Ser-1067 and Ser-1083 in vivo. Ser-1083 phosphorylation is IR-inducible, depends on ATM and Nijmegen breakage syndrome 1 (NBS1), and is required for intra-S phase checkpoint. Interestingly, Ser-1067 phosphorylation is constitutive and is not induced by IR but also affects intra-S phase checkpoint. Phosphorylation of Ser-1083 is weakened in cells expressing S1067A mutant, suggesting interplay between Ser-1067 and Ser-1083 phosphorylation in DNA damage response. Consistently, small interfering RNA knockdown of CK2 leads to attenuated phosphorylation of Ser-1067 as well as intra-S phase checkpoint defect. Our data provide evidence that phosphorylation of a core cohesin subunit SMC3 by ATM plays an important role in DNA damage response and suggest that a constitutive phosphorylation by CK2 may affect intra-S phase checkpoint by modulating SMC3 phosphorylation by ATM.     

A LC-MS/MS method for the specific, sensitive, and simultaneous quantification of 5-aminolevulinic acid and porphobilinogen

Accurate determinations of 5-aminolevulinic acid (ALA) and porphobilinogen (PBG) in physiologic fluids are required for the diagnosis and therapeutic monitoring of acute porphyrias. Current colorimetric methods are insensitive and over-estimate ALA and PBG due to poor specificity, while LC-MS/MS methods increase sensitivity, but have limited matrices. An LC-MS/MS method was developed to simultaneously determine ALA and PBG concentrations in fluids or tissues which were solid phase extracted, butanol derivatized, and quantitated by selective reaction monitoring using (13)C(5), (15)N-ALA and 2,4-(13)C(2)-PBG internal standards. ALA was separated from interfering compounds on a reverse phase C8-column. For ALA and PBG, the matrix effects (87.3-105%) and process efficiencies (77.6-97.8% and 37.2-41.6%, respectively) were acceptable in plasma and urine matrices. The assay was highly sensitive for ALA and PBG (LLOQ=0.05 μM with 25 μL urine or 100 μL plasma), and required ～4 h from extraction to results. ALA and PBG accuracy ranged from 88.2 to 110% (n=10); intra- and inter-assay coefficients of variations were <10% for urine and plasma. In clinical applications, patients with mutation-confirmed acute porphyrias had normal to slightly increased urinary ALA and PBG levels when asymptomatic, and high levels during acute attacks, which decreased with hemin therapy. In AIP mice, baseline ALA and PBG levels in urine, plasma, and liver were increased after phenobarbital induction 28-/63-, 42-/266-, and 13-/316-fold, respectively. This LC-MS/MS method is rapid, specific, highly sensitive, accurate, and simultaneously measures ALA and PBG in urine, plasma, and tissues permitting porphyria clinical diagnoses, therapeutic monitoring, and research.     

The response of plasma membrane lipid composition in callus of the halophyte Spartina patens (Poaceae) to salinity stress

Callus cultures of the salt marsh grass Spartina patens were examined to determine changes and consistencies in membrane lipid composition in response to salt. Major membrane lipid classes remained stable at all salinity levels (0, 170, 340 mmol/L). However, the membrane protein to lipid ratio decreased significantly in response to elevated NaCl. Callus plasma membrane (PM) consisted predominantly of sterols, about 60% (mol%) of the total lipids. Glycolipid was the second largest lipid class, making up about 20% (mol%) of the total. With increasing salinity, the relative percentage of sitosterol decreased, while that of campesterol increased. The phospholipid species detected were phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylinositol (PI). When callus was grown at 340 mmol/L NaCl, PC increased significantly. PI and PS were also significantly elevated in salinity treatments. Only 24-32% of the PM fatty acids were common plant membrane fatty acids, C16, C18, C20, and C22, while over 60% were the less common fatty acids, C11 and C14. Membrane fluidity remained stable in response to growth medium salinity. The findings on membrane responses to salinity will facilitate a better understanding of this halophyte's tactics for salt tolerance.     

Stress tolerance in the marsh plant Spartina patens: Impact of NaCl on growth and root plasma membrane lipid composition

The C‐4 salt marsh grass, Spartina patens , thrives in the upper portion of the marsh where soil salinities may be equal to coastal seawater. Spartina patens was grown in hydroponic culture in a greenhouse at 0, 340, and 510 m M NaCl, and measured for growth, tissue cation content, and root plasma membrane (PM) lipid composition. From 0 to 340 and 510 m M , the shoot growth decreased, but root growth was not affected. The Na⁺ content increased in both shoots and roots when plants were grown in salt, while the shoots had a decreased K⁺ content and the roots had a decreased Ca²⁺ content. Spartina patens root plasma membrane was isolated with an aqueous polymer two‐phase system. The purity of the plasma membrane was verified with cytochemical tests on membrane enzyme markers. Plasma membrane lipids were stable relative to the membrane protein content. Molar percentages of sterols (including free sterols) and phospholipid decreased with increasing salinity. However, glycolipid showed a statistically significant increase in the total lipid as salinity in the medium was increased from 0 to 510 m M . Even at a salinity of 510 m M , the plasma membrane sterol/phospholipid ratio was unaffected by NaCl. When the plants were grown in NaCl media, the plasma membrane had a decreased phosphatidylcholine (PC) and phosphatidylethanolamine (PE) content, but the PC/PE ratios were not affected. The plasma membrane molar percentage of sitosterol in total free sterol increased when plants were grown in salt media. The predominant membrane fatty acids were C11 and C14, and the major unsaturated one was C14:1. An increase in growth medium salinity resulted in a decreased root plasma membrane fluidity.