Microplastic abundance, distribution and composition in the mid-west Pacific Ocean.

Microplastic pollution is widespread across most ocean basins around the world. Microplastics (MPs) are small plastic particles that have a significant impact on the marine environment. Various research on plastic pollution have been conducted in several regions. However, currently, there is limited data on the distribution and concentration of MPs in the mid-west Pacific Ocean. Therefore, this study we investigated the abundance, distribution, characteristics, and compositions of MPs in this region. Sea surface water samples collected from 18 stations showed a microplastic concentration range of 6028-95,335 pieces/km2 and a mean concentration of 34,039 ± 25,101 pieces/km2. Highest microplastic concentrations were observed in the seamount region of western Pacific. We observed a significant positive correlation between microplastic abundance and latitude across the study region. It was observed that microplastic concentrations decreased with increasing offshore distance at sites located on a 154° W transect. Fibres/filaments were the dominant microparticles observed in this study (57.4%), followed by fragments (18.3%). The dominant particle size range was 1-2.5 mm (35.1%), followed by 0.5-1 mm (28.5%), and the dominant particle colour was white (33.8%), followed by transparent (31.0%) and green (24.6%). The most common polymer identified by µ-Raman was polypropylene (39.1%), followed by polymethyl methacrylate (16.2%), polyethylene (14.1%) and polyethylene terephthalate (14.2%). The possible sources and pathways of microplastics in the study area were proposed based on the morphological and compositional characteristics of particles, their spatial distribution patterns, and shipboard current profiling (ADCP). Our study contributes to the further understanding of MPs in remote ocean areas.

Association between class III ß-tubulin expression and response to paclitaxel/vinorebine-based chemotherapy for non-small cell lung cancer: a meta-analysis.

BACKGROUND: It has been proposed that the level of class III ß-tubulin gene expression can be used to predict clinical sensitivity to paclitaxel/vinorebine-based chemotherapy in non-small cell lung cancer (NSCLC) patients. However, whereas there are published reports supporting this association, there are also reports of studies that failed to find such an association. We conducted a meta-analysis of all relevant published data to provide a combined statistical assessment of the proposed association of expression variations of class III ß-tubulin with objective response and median survival in patients with NSCLC treated with paclitaxel/vinorebine-based chemotherapy. METHODS: We conducted the meta-analysis using data from ten studies, each of which evaluated the correlation between class III ß-tubulin expression levels and objective response in patients treated with paclitaxel/vinorebine-based chemotherapy for NSCLC patients. All eligible studies were searched by MEDLINE, EMBASE and CNKI databases. Overall odds ratios (ORs) of the objective response were calculated using the method of Mantel-Haenszel. The differences in objective responses between Caucasian and Asian patients treated with paclitaxel/vinorebine-based chemotherapy were compared. We also compared outcomes for patients treated with paclitaxel to those treated with vinorebine. RESULTS: There were a total of 552 patients in the ten studies that met our criteria for evaluation. High/positive expression of class III ß-tubulin was found in 279 patients (50.5%), and low/negative expression for this gene was found in 273 (49.5%) patients. The objective response rate for paclitaxel/vinorebine-based chemotherapy was significantly higher in patients with low/negative class III ß-tubulin expression (OR=0.28; 95% CI, 0.20-0.41; P<0.00001). Median survival time was longer for patients with low/negative expression of class III ß-tubulin compared with patients with high/positive expression (MR=1.40; CI, 0.89-0.90; P<0.00001). There was no significant difference in therapy between Caucasian and Asian patients treated with paclitaxel/vinorebine-based chemotherapy (Chi(2)=0.02, P=0.88). In our analysis, NSCLC patients treated with paclitaxel had more favorable clinical outcomes than those treated with vinorelbine (Chi(2)=3.69, P=0.05). CONCLUSIONS: By combining data from ten different studies, we found a correlation between low TUBB3 gene expression and favorable clinical outcome to anti-tubulin therapy. The correlation for the combined data was significantly stronger than it was for any of the individual studies. This result supports the usefulness of class III ß-tubulin mRNA level as a biomarker for sensitivity to paclitaxel/vinorebine-based chemotherapy in NSCLC patients.

Gadd45a regulates matrix metalloproteinases by suppressing DeltaNp63alpha and beta-catenin via p38 MAP kinase and APC complex activation.

The p53-regulated growth arrest and DNA damage-inducible gene product Gadd45a has been recently identified as a key factor protecting the epidermis against ultraviolet radiation (UVR)-induced skin tumors by activating p53 via the stress mitogen-activated protein kinase (MAPK) signaling pathway. Herein we identify Gadd45a as an important negative regulator of two oncogenes commonly over-expressed in epithelial tumors: the p53 homologue DeltaNp63alpha and beta-catenin. DeltaNp63alpha is one of the several p63 isoforms and is the predominant species expressed in basal epidermal keratinocytes. DeltaNp63alpha lacks the N-terminal transactivation domain and behaves as a dominant-negative factor blocking expression of several p53-effector genes. DeltaNp63alpha also associates with and blocks activation of the adenomatous polyposis coli (APC) destruction complex that targets free cytoplasmic beta-catenin for degradation. While most beta-catenin protein is localized to the cell membrane and is involved in cell-cell adhesion, accumulation of free cytoplasmic beta-catenin will translocate into the nucleus where it functions in a bipartite transcription factor complex, whose targets include invasion and metastasis promoting endopeptidases, matrix metalloproteinases (MMP). We show that Gadd45a not only directly associates with two components of the APC complex, namely protein phosphatase 2A (PP2A) and glycogen synthase kinase 3beta (GSK3beta) but also promotes GSK3beta dephosphorylation at Ser9, which is essential for GSK3beta activation, and resultant activation of the APC destruction complex. We demonstrate that lack of Gadd45a not only prevents DeltaNp63alpha suppression and GSK3beta dephosphorylation but also prevents free cytoplasmic beta-catenin degradation after UV irradiation. The inability of Gadd45a-null keratinocytes to suppress beta-catenin may contribute to the resulting observation of increased MMP expression and activity along with significantly faster keratinocyte migration in Matrigel in vitro and accelerated wound closure in vivo. Furthermore, epidermal keratinocytes treated with p38 MAPK inhibitors, both in vivo and in vitro, behave very similarly to Gadd45a-null keratinocytes after UVR. Similarly, Trp53-null mice are unable to attenuate DeltaNp63alpha expression in epidermal keratinocytes after such stress. These findings demonstrate a dependence on Gadd45a-mediated p38 MAPK and p53 activation for proper modulation of DeltaNp63alpha, GSK3beta, and beta-catenin after irradiation. Taken together, our results indicate that Gadd45a is able to repress DeltaNp63alpha, beta-catenin, and consequently MMP expression by two means: by maintaining UVR-induced p38 MAPK and p53 activation and also by associating with the APC complex. This implicates Gadd45a in the negative regulation of cell migration, and invasion.