Influence of Arsenate on Lipid Peroxidation Levels and Antioxidant Enzyme Activities in Bacillus cereus Strain XZM002 Isolated from High Arsenic Aquifer Sediments

Bacillus cereus strain XZM002 isolated from high arsenic aquifer sediments of Datong Basin was applied to examine the effects of arsenate stress on antioxidant enzyme activities, lipid peroxidation levels and cell growth inhibition rate. After 2 d exposure, the cell growth inhibition rate enhanced with an increase of As(V) concentrations (0, 800, 1600 μg/l). Reactive oxygen species and glutathione contents, lipid peroxidation levels, and antioxidant enzymes (glutathione peroxidase, and other three) activities of the treated cells were significantly higher than those of the controls during 3 d exposure (p < 0.05). Besides, the levels of nine parameters reached maximum after 2 d exposure and increased significantly with increasing arsenate stress (p < 0.05). However, they returned to levels similar to those of the control on the fourth day of exposure. The results suggested that the antioxidant defense system in B. cereus strain XZM002 could protect the cells from oxidative damage induced by arsenate.     

Negative Regulation of Interferon-induced Transmembrane Protein 3 by SET7-mediated Lysine Monomethylation

Although lysine methylation is classically known to regulate histone function, its role in modulating antiviral restriction factor activity remains uncharacterized. Interferon-induced transmembrane protein 3 (IFITM3) was found monomethylated on its lysine 88 residue (IFITM3-K88me1) to reduce its antiviral activity, mediated by the lysine methyltransferase SET7. Vesicular stomatitis virus and influenza A virus infection increased IFITM3-K88me1 levels by promoting the interaction between IFITM3 and SET7, suggesting that this pathway could be hijacked to support infection; conversely, IFN-α reduced IFITM3-K88me1 levels. These findings may have important implications in the design of therapeutics targeting protein methylation against infectious diseases.     

PI3K and Notch signal pathways coordinately regulate the activation and proliferation of T lymphocytes in asthma

AimsIn the present study, we determined whether Phosphoinositide 3-kinase (PI3K) and Notch signal pathways are involved in the expression of cyclinD1, cyclinA and p27kip1 which were key molecules in controlling cell cycling from CD4⁺ T lymphocyte in animal model of asthma.Main methodsOvalbumin (OVA) sensitized murine model of asthma was used to investigate the expression of cyclin D1, cyclin A, and p27kip1 by splenic CD4⁺ T lymphocytes. We further observed the effect of specific inhibitor of PI3K(LY294002) and specific inhibitor of Notch(DAPT) on the proliferation of such CD4⁺ T lymphocytes.Key findingsWe found that the expression of cyclinD1 and cyclinA was upregulated at both protein and mRNA levels in asthma group while p27kip1 was down-regulated. Both LY294002 and DAPT inhibit the proliferation of CD4⁺ T lymphocytes in a time- and dose-dependent manner. Furthermore, LY294002 and DAPT have additive effect in down-regulation of cyclinD1 and upregulation of p27kip1. An upregulation of cyclinA, although not statistically significant, was also observed.SignificanceThese data suggested that PI3K signal pathway and Notch signal pathway may coordinately regulate the cell proliferation and differentiation processes through up-regulating cyclinD1 and down-regulating p27kip1 of CD4⁺ T lymphocytes.     

Lentiviral-mediated transfer of CDNF promotes nerve regeneration and functional recovery after sciatic nerve injury in adult rats

Peripheral nerve injury is often followed by incomplete and unsatisfactory functional recovery and may be associated with sensory and motor impairment of the affected limb. Therefore, a novel method is needed to improve the speed of recovery and the final functional outcome after peripheral nerve injuries. This report investigates the effect of lentiviral-mediated transfer of conserved dopamine neurotrophic factor (CDNF) on regeneration of the rat peripheral nerve in a transection model in vivo. We observed notable overexpression of CDNF protein in the distal sciatic nerve after recombinant CDNF lentiviral vector application. We evaluated sciatic nerve regeneration after surgery using light and electron microscopy and the functional recovery using the sciatic functional index and target muscle weight. HE staining revealed better ordered structured in the CDNF-treated group at 8 weeks post-surgery. Quantitative analysis of immunohistochemistry of NF200 and S-100 in the CDNF group revealed significant improvement of axonal and Schwann cell regeneration compared with the control groups at 4 weeks and 8 weeks after injury. The thickness of the myelination around the axons in the CDNF group was significantly higher than in the control groups at 8 weeks post-surgery. The CDNF group displayed higher muscle weights and significantly increased sciatic nerve index values. Our findings suggest that CDNF gene therapy could provide durable and stable CDNF protein concentration and has the potential to enhance peripheral nerve regeneration, morphological and functional recovery following nerve injury, which suggests a promising strategy for peripheral nerve repair.     

C-Myc negatively controls the tumor suppressor PTEN by upregulating miR-26a in glioblastoma multiforme cells

The c-Myc oncogene is amplified in many tumor types. It is an important regulator of cell proliferation and has been linked to altered miRNA expression, suggesting that c-Myc-regulated miRNAs might contribute to tumor progression. Although miR-26a has been reported to be upregulated in glioblastoma multiforme (GBM), the mechanism has not been established. We have shown that ectopic expression of miR-26a influenced cell proliferation by targeting PTEN, a tumor suppressor gene that is inactivated in many common malignancies, including GBM. Our findings suggest that c-Myc modulates genes associated with oncogenesis in GBM through deregulation of miRNAs via the c-Myc–miR-26a–PTEN signaling pathway. This may be of clinical relevance.     

Discovery of TAK-960: An orally available small molecule inhibitor of polo-like kinase 1 (PLK1)

Using structure-based drug design, we identified and optimized a novel series of pyrimidodiazepinone PLK1 inhibitors resulting in the selection of the development candidate TAK-960. TAK-960 is currently undergoing Phase I evaluation in adult patients with advanced solid malignancies.     

Improved inhibitory activities against tumor-cell migration and invasion by 15-benzylidene substitution derivatives of andrographolide

In the present study, andrographolide (Andro, 1) derivatives were screened to identify potent inhibitors against tumor-cell migration and invasion, and associated structure–activity relationships were studied. Compared to 1, compounds 8a–8d exhibited more potent activities against migration in SGC-7901, PC-3, A549, HT-29 and Ec109 cell lines. Improved activities against tumor-cell migration and invasion were proved to be associated with the down-regulation of MMPs.     

Phylogeography of Sophora davidii (Leguminosae) across the ‘Tanaka‐Kaiyong Line’, an important phytogeographic boundary in Southwest China

The ‘Tanaka‐Kaiyong Line’ (TKL) is a major phytogeographic boundary in Southwest China, separating East Asia's Sino‐Himalayan and Sino‐Japanese Floras. However, little is known about the importance of this boundary in promoting intraspecific phylogeographic subdivision and divergence. Using chloroplast (cpDNA) and nuclear‐intron (nDNA) sequence data, we reconstructed the population history of Sophora davidii, a drought‐tolerant riparian shrub widely distributed on either side of the TKL. Specifically, we aimed at testing two long‐standing explanations for possible vicariant events across the TKL: (i) Late Pliocene (c. 3 Ma) geological uplift of the eastern Qinghai‐Tibetan Plateau (QTP) or (ii) a sharp environmental gradient associated with the establishment of different monsoon regimes on either side of the TKL during the (Late) Pleistocene. Our genealogical analyses detected a major west–east split in cpDNA, geographically largely consistent with the TKL, and dated to c. 1.28 Ma (95% HPD: 0.21–2.96 Ma), hence postdating the latest phase of eastern QTP uplift. Furthermore, integrating cpDNA phylogeographic patterns with mismatch analyses, we found multiple refugial isolation and long‐term demographic stability of populations in the west (Hengduan Mountain Range) compared with extensive range expansions in the east, possibly during the last glacial period(s) and followed by differentiation into regional sublineages (southeast: Yunnan‐Guizhou Plateau vs. northeast: Qinling Mts./Loess Plateau). Although nuclear differentiation was less marked, the geographical pattern of nDNA haplotypes provided some further indication of the species' eastward expansion, possibly from source populations located just east of the TKL (lower Jinshajiang region). Overall, the present data reject the geological (tectonic) explanation for the TKL and, instead, provide supportive evidence for its role as a climatically driven barrier to present‐day plant dispersal. In addition, our study highlights changing temperatures and vegetation types during the last glacial period(s), along with aspects of regional topography, to be important determinants of the glacial eastward expansion of S. davidii. In consequence, our study lends support to a ‘glacial out‐of‐Hengduan Mts’. hypothesis for the xerophytic‐riparian flora of Southwest China, which in turn is inconsistent with the traditional view of the TKL as a ‘classical’ vicariant‐biogeographic boundary.     

Impact of GC content on gene expression pattern in chicken

Background

GC content varies greatly between different genomic regions in many eukaryotes. In order to determine whether this organization named isochore organization influences gene expression patterns, the relationship between GC content and gene expression has been investigated in man and mouse. However, to date, this question is still a matter for debate. Among the avian species, chicken (Gallus gallus) is the best studied representative with a complete genome sequence. The distinctive features and organization of its sequence make it a good model to explore important issues in genome structure and evolution.

Methods

Only nuclear genes with complete information on protein-coding sequence with no evidence of multiple-splicing forms were included in this study. Chicken protein coding sequences, complete mRNA sequences (or full length cDNA sequences), and 5^′ untranslated region sequences (5^′ UTR) were downloaded from Ensembl and chicken expression data originated from a previous work. Three indices i.e. expression level, expression breadth and maximum expression level were used to measure the expression pattern of a given gene. CpG islands were identified using hgTables of the UCSC Genome Browser. Correlation analysis between variables was performed by SAS Proprietary Software Release 8.1.

Results

In chicken, the GC content of 5^′ UTR is significantly and positively correlated with expression level, expression breadth, and maximum expression level, whereas that of coding sequences and introns and at the third coding position are negatively correlated with expression level and expression breadth, and not correlated with maximum expression level. These significant trends are independent of recombination rate, chromosome size and gene density. Furthermore, multiple linear regression analysis indicated that GC content in genes could explain approximately 10% of the variation in gene expression.

Conclusions

GC content is significantly associated with gene expression pattern and could be one of the important regulation factors in the chicken genome.