Effects of sap velocity on the daytime increase of stem CO2 efflux from stems of Schima superba trees

Stem CO₂ efflux (E _s) has been estimated from a temperature-related equation, but sap flux often affects measurements of E _s, which leads to misunderstanding real stem respiration. In order to observe the relationship between E _s and stem temperature and to analyze the effect of sap velocity on E _s, stem temperature, E _s and sap flux were measured from a subtropical Schima superba plantation in South China on three trees for consecutive 3 days in July and October 2009. Stem temperature, E _s and sap velocity were significantly higher in July than in October. Stem temperature could explain 17–41 and 54–75% variations of E _s in July and October, respectively. A negative relationship between E _s and stem temperature was found during 1800–2300 hours in July. The daytime E _s was 9.2, 4.3 and 2.4% higher than the predicted for three trees in July, and this occurred only on Tree 1 in October. Sap velocity was positively correlated with E _s for three trees in July, and the increase of E _s with the increase of sap velocity was only observed on Tree 1 in October. These results demonstrated that the occurrence of sap flux could account for the increase of daytime E _s, and the effect of sap velocity on E _s varied with the seasons from the S. superba stem.     

Etoposide phosphate enhances the acetylation level of translation elongation factor 1A in PLC5 cells

Translation elongation factor 1A (eEF1A) is a factor critically involved in the process of protein synthesis. The activity of eEF1A has been shown by several studies to be regulated by post-translational modifications such as phosphorylation and dephosphorylation. However, until now less research has focused on other post-translational modifications of eEF1A, especially acetylation. In this report, we provide new evidence for the existence of eEF1A acetylation in PLC5 cells by immunoprecipitation and Western blotting. Using the histone deacetylase (HDAC) inhibitor trichostatin A (TSA), we found that the deacetylation of eEF1A is mainly attributable to classes I and II HDAC rather than class III HDAC, and, furthermore, that the antitumour agent etoposide phosphate (VP 16) enhances the acetylation of eEF1A in a synergistic way with TSA. Our data suggest the possibility that the increased acetylation of eEF1A could be a new mechanism for the antitumour effect of etoposide.     

Prediction of lysine ubiquitination with mRMR feature selection and analysis

Ubiquitination, one of the most important post-translational modifications of proteins, occurs when ubiquitin (a small 76-amino acid protein) is attached to lysine on a target protein. It often commits the labeled protein to degradation and plays important roles in regulating many cellular processes implicated in a variety of diseases. Since ubiquitination is rapid and reversible, it is time-consuming and labor-intensive to identify ubiquitination sites using conventional experimental approaches. To efficiently discover lysine-ubiquitination sites, a sequence-based predictor of ubiquitination site was developed based on nearest neighbor algorithm. We used the maximum relevance and minimum redundancy principle to identify the key features and the incremental feature selection procedure to optimize the prediction engine. PSSM conservation scores, amino acid factors and disorder scores of the surrounding sequence formed the optimized 456 features. The Mathew’s correlation coefficient (MCC) of our ubiquitination site predictor achieved 0.142 by jackknife cross-validation test on a large benchmark dataset. In independent test, the MCC of our method was 0.139, higher than the existing ubiquitination site predictor UbiPred and UbPred. The MCCs of UbiPred and UbPred on the same test set were 0.135 and 0.117, respectively. Our analysis shows that the conservation of amino acids at and around lysine plays an important role in ubiquitination site prediction. What’s more, disorder and ubiquitination have a strong relevance. These findings might provide useful insights for studying the mechanisms of ubiquitination and modulating the ubiquitination pathway, potentially leading to potential therapeutic strategies in the future.     

Zinc deficiency exacerbates diabetic down-regulation of Akt expression and function in the testis: essential roles of PTEN, PTP1B and TRB3

Since zinc (Zn) plays an important role in the spermatogenesis and Zn deficiency exacerbated diabetes-induced testicular apoptosis, the present study investigated the effect of Zn deficiency on diabetes-induced testicular Akt-mediated glucose metabolism changes and inflammation. Zn deficiency was induced by chronic treatment of normal and diabetic mice with the Zn chelator N,N,N',N', tetrakis (2-pyridylmethyl) ethylenediaminepentaethylene (TPEN). After diabetes onset induced by streptozotocin, both diabetic and age-matched control mice were given TPEN intraperitoneally for 4 months. Western blotting assay revealed that Akt-mediated glucose metabolism signaling was down-regulated in the diabetic testis and was further decreased in diabetic mice with Zn deficiency, reflected by reduced phosphorylation of both Akt and GSK-3β and increased phosphorylation of glycogen synthase along with a disarrangement of fatty acid metabolism (increased expression of PPAR-α and decreased adenosine-monophosphate-activated protein kinase phosphorylation). Testicular expressions of plasminogen activator inhibitor-1 and intracellular adhesion molecule-1 as inflammatory factors were increased in the TPEN or diabetes-alone group, but not additive in the group of diabetes with Zn deficiency. A mechanistic study showed that Akt negative regulators phosphatase and tensin homology deleted on chromosome 10 (PTEN), protein tyrosine phosphatases 1B and Tribbles 3 all increased in diabetic testis and further increased in the testis of diabetic mice with Zn deficiency. These studies suggest that Zn deficiency significantly exacerbated diabetic down-regulation of Akt expression and function, most likely by up-regulation of Akt negative regulators. Therefore, prevention of Zn deficiency for diabetic patients is important in order to avoid the exacerbation of diabetic inhibition of glucose metabolism in the testis.     

Detection of water toxicity using cytochrome P450 transgenic zebrafish as live biosensor: for polychlorinated biphenyls toxicity

Cytochrome P450 (CYPs) is significant in degradation of endogenous substrates and detoxification of carcinogens, therefore it is a biomarker for assessment of polycyclic aromatic hydrocarbons (PAHs) level in aquatic environment. In the present study, a transgenic line of zebrafish had been generated using a CYP-green fluorescence protein (CYP-GFP) construct, driven by CYP1A1 promoter. Polychlorinated biphenyls (PCBs) were used as toxicant, in concentrations of 0.02 μg/ml, 0.04 μg/ml, 0.08 μg/ml, 0.4 μg/ml, and 0.8 μg/ml. The transgenic control fish showed low intensity of fluorescence in the liver. After exposed to PCBs, zebrafish had morphological changes such as expansion of yolk, contortion of tails and inflation of pericardial area. Green fluorescence signals were found to express according to concentrations and time. The green fluorescence signal was most intense after treatment with 0.08 μg/ml PCBs. However, the maximum area of green fluorescent signal was found at 0.04 μg/ml PCBs. GFP started to express at 3h exposure to PCBs, increasing its intensity until 6 h exposure, and then level off. Since the GFP expression is fast responding and is sensitive to low PAHs concentrations, transgenic fish is a good tool for live imaging and monitoring of aquatic contamination.     

Short cyclic peptides derived from the C-terminal sequence of α1-antitrypsin exhibit significant anti-HIV-1 activity

Serpin A1 (α1-AT), the largest subgroup of serpins, presents in human plasma at high concentration and plays important regulatory roles in physiological and pathological processes. Accumulated evidence suggests that α1-AT may play a role in controlling HIV-1 infection. In this study, we designed and synthesized a set of short linear peptides derived from the C-terminal sequence of α1-AT. Since none of them showed significant anti-HIV-1 activity, we proceeded to synthesize four short cyclic peptides having 7 amino acids, and we found that three of them exhibited significant anti-HIV-1 activity. One of these cyclic peptides, designated CPM, inhibited HIV-1 entry and infection at low μM level, indicating that these short cyclic peptides could serve as leads for the development of novel anti-HIV-1 therapeutics.     

Discovery of HIV fusion inhibitors targeting gp41 using a comprehensive α-helix mimetic library

The evaluation of a comprehensive α-helix mimetic library for binding the gp41 NHR hydrophobic pocket recognizing an intramolecular CHR α-helix provided a detailed depiction of structural features required for binding and led to the discovery of small molecule inhibitors (K(i) 0.6-1.3 μM) that not only match or exceed the potency of those disclosed over the past decade, but that also exhibit effective activity in a cell-cell fusion assay (IC(50) 5-8 μM).     

Identification of a phenylacylsulfonamide series of dual Bcl-2/Bcl-xL antagonists

A series of phenylacylsulfonamides has been prepared as antagonists of Bcl-2/Bcl-xL. In addition to potent binding affinities for both Bcl-2 and Bcl-xL, these compounds were shown to induce classical markers of apoptosis in isolated mitochondria. Overall weak cellular potency was improved by the incorporation of polar functionality resulting in compounds with moderate antiproliferative activity.     

The use of next generation sequencing technology to study the effect of radiation therapy on mitochondrial DNA mutation

The human mitochondrial genome has an exclusively maternal mode of inheritance. Mitochondrial DNA (mtDNA) is particularly vulnerable to environmental insults due in part to an underdeveloped DNA repair system, limited to base excision and homologous recombination repair. Radiation exposure to the ovaries may cause mtDNA mutations in oocytes, which may in turn be transmitted to offspring. We hypothesized that the children of female cancer survivors who received radiation therapy may have an increased rate of mtDNA heteroplasmy mutations, which conceivably could increase their risk of developing cancer and other diseases. We evaluated 44 DNA blood samples from 17 Danish and 1 Finnish families (18 mothers and 26 children). All mothers had been treated for cancer as children and radiation doses to their ovaries were determined based on medical records and computational models. DNA samples were sequenced for the entire mitochondrial genome using the Illumina GAII system. Mother's age at sample collection was positively correlated with mtDNA heteroplasmy mutations. There was evidence of heteroplasmy inheritance in that 9 of the 18 families had at least one child who inherited at least one heteroplasmy site from his or her mother. No significant difference in single nucleotide polymorphisms between mother and offspring, however, was observed. Radiation therapy dose to ovaries also was not significantly associated with the heteroplasmy mutation rate among mothers and children. No evidence was found that radiotherapy for pediatric cancer is associated with the mitochondrial genome mutation rate in female cancer survivors and their children.