A novel class of CoA-transferase involved in short-chain fatty acid metabolism in butyrate-producing human colonic bacteria

Peer reviewedPublisher PD

Inhibition of HIF-1α by the anticancer drug TAS106 enhances X-ray-induced apoptosis in vitro and in vivo

In a previous study, we showed that a novel anticancer drug, 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)cytosine (TAS106, ECyd) increased the antitumour efficacy of X-irradiation. However, its effects on hypoxic cells in tumours remain unclarified. Here, we show that TAS106 enhances the induction of apoptosis in X-irradiated human gastric adenocarcinoma MKN45 and MKN28 cells under hypoxia in vitro. At the same time, the accumulation of HIF-1α observed under hypoxia was shown to be decreased to the level of normoxia in the presence of 0.1 μM TAS106. To study the function of HIF-1α protein in apoptosis of hypoxic cells, we employed an HIF-1α reductive approach using its specific antisense oligodeoxynucleotide. The reduction of HIF-1α gene expression dramatically enhanced X-ray-induced apoptosis in hypoxic cells. In in vivo experiments in which MKN45 cells were transplanted into severe combined immunodeficient (SCID) mice, TAS106 (0.5 mg kg−1) suppressed HIF-1α expression and subsequently reduced the area of the hypoxic region in the tumour and enhanced the induction of apoptosis in the hypoxic region when combined with 2 Gy of X-irradiation. These results suggest the possibility that TAS106 acts as a potent radiosensitiser through the inhibition of HIF-1α expression and can be a useful agent against radiotherapy-resistant hypoxic cells in solid tumours

An evaluation of ocean color model estimates of marine primary productivity in coastal and pelagic regions across the globe

Abstract. Nearly half of the earth’s photosynthetically fixed carbon derives from the oceans. To determine global and region specific rates, we rely on models that estimate marine net primary productivity (NPP) thus it is essential that these models are evaluated to determine their accuracy. Here we assessed the skill of 21 ocean color models by comparing their estimates of depth-integrated NPP to 1156 in situ 14C measurements encompassing ten marine regions including the Sargasso Sea, pelagic North Atlantic, coastal Northeast Atlantic, Black Sea, Mediterranean Sea, Arabian Sea, subtropical North Pacific, Ross Sea, West Antarctic Peninsula, and the Antarctic Polar Frontal Zone. Average model skill, as determined by root-mean square difference calculations, was lowest in the Black and Mediterranean Seas, highest in the pelagic North Atlantic and the Antarctic Polar Frontal Zone, and intermediate in the other six regions. The maximum fraction of model skill that may be attributable to uncertainties in both the input variables and in situ NPP measurements was nearly 72%. On average, the simplest depth/wavelength integrated models performed no worse than the more complex depth/wavelength resolved models. Ocean color models were not highly challenged in extreme conditions of surface chlorophyll-a and sea surface temperature, nor in high-nitrate low-chlorophyll waters. Water column depth was the primary influence on ocean color model performance such that average skill was significantly higher at depths greater than 250 m, suggesting that ocean color models are more challenged in Case-2 waters (coastal) than in Case-1 (pelagic) waters. Given that in situ chlorophyll-a data was used as input data, algorithm improvement is required to eliminate the poor performance of ocean color NPP models in Case-2 waters that are close to coastlines. Finally, ocean color chlorophyll-a algorithms are challenged by optically complex Case-2 waters, thus using satellite-derived chlorophyll-a to estimate NPP in coastal areas would likely further reduce the skill of ocean color models

An assessment of phytoplankton primary productivity in the Arctic Ocean from satellite ocean color/in situ chlorophyll-a based models

We investigated 32 net primary productivity (NPP) models by assessing skills to reproduce integrated NPP in the Arctic Ocean. The models were provided with two sources each of surface chlorophyll-a concentration (chlorophyll), photosynthetically available radiation (PAR), sea surface temperature (SST), and mixed-layer depth (MLD). The models were most sensitive to uncertainties in surface chlorophyll, generally performing better with in situ chlorophyll than with satellite-derived values. They were much less sensitive to uncertainties in PAR, SST, and MLD, possibly due to relatively narrow ranges of input data and/or relatively little difference between input data sources. Regardless of type or complexity, most of the models were not able to fully reproduce the variability of in situ NPP, whereas some of them exhibited almost no bias (i.e., reproduced the mean of in situ NPP). The models performed relatively well in low-productivity seasons as well as in sea ice-covered/deep-water regions. Depth-resolved models correlated more with in situ NPP than other model types, but had a greater tendency to overestimate mean NPP whereas absorption-based models exhibited the lowest bias associated with weaker correlation. The models performed better when a subsurface chlorophyll-a maximum (SCM) was absent. As a group, the models overestimated mean NPP, however this was partly offset by some models underestimating NPP when a SCM was present. Our study suggests that NPP models need to be carefully tuned for the Arctic Ocean because most of the models performing relatively well were those that used Arctic-relevant parameters

Association of polymorphisms in survivin gene with the risk of hepatocellular carcinoma in Chinese han population: a case control study

<p>Abstract</p> <p>Background</p> <p>Survivin, one of the strongest apoptosis inhibitors, plays a critical role in the development and progression of hepatocellular carcinoma (HCC). By comparison, relatively little is known about the effect of <it>survivin </it>gene polymorphisms on HCC susceptibility. Our study aimed to investigate the association of <it>survivin </it>gene polymorphisms with the risk of HCC in Chinese han population.</p> <p>Methods</p> <p>A case-control study was conducted in Chinese han population consisting of 178 HCC cases and 196 cancer-free controls. Information on demographic data and related risk factors was collected for all subjects. Polymorphisms of the <it>survivin </it>gene, including three loci of rs8073069, rs9904341 and rs1042489, were selected and genotyped by a polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) technique. Association analysis of genotypes/alleles and haplotypes from these loci with the risk of HCC was conducted under different genetic models.</p> <p>Results</p> <p>Using univariate analysis of rs8073069, rs9904341 and rs1042489 under different genetic models, no statistically significant difference was found in genotype or allele distribution of HCC cases relative to the controls (<it>P </it>> 0.05). Linkage disequilibrium (LD) analysis showed that these loci were in LD. Multivariate logistic regression indicated that with no G-C-T haplotype as reference, the haplotype of G-C-T from these loci was associated with a lower risk for HCC under the recessive model (<it>OR = </it>0.46, 95% confidence interval (<it>CI</it>): 0.24~0.90, <it>P </it>= 0.023). Both HBsAg+ and the medical history of viral hepatitis type B were risk factors for HCC. However, no statistically significant haplotype-environment interaction existed.</p> <p>Conclusions</p> <p>No association between rs8073069, rs9904341 or rs1042489 in <it>survivin </it>gene and the risk of HCC is found in Chinese han population, but rs8073069G-rs9904341C- rs1042489T is perhaps a protective haplotype for HCC.</p

A case of polymicrogyria in macaque monkey: impact on anatomy and function of the motor system

Background: Polymicrogyria is a malformation of the cerebral cortex often resulting in epilepsy or mental retardation. It remains unclear whether this pathology affects the structure and function of the corticospinal (CS) system. The anatomy and histology of the brain of one macaque monkey exhibiting a spontaneous polymicrogyria (PMG monkey) were examined and compared to the brain of normal monkeys. The CS tract was labelled by injecting a neuronal tracer (BDA) unilaterally in a region where low intensity electrical microstimulation elicited contralateral hand movements (presumably the primary motor cortex in the PMG monkey). Results: The examination of the brain showed a large number of microgyri at macro- and microscopic levels, covering mainly the frontoparietal regions. The layered cortical organization was locally disrupted and the number of SMI-32 stained pyramidal neurons in the cortical layer III of the presumed motor cortex was reduced. We compared the distribution of labelled CS axons in the PMG monkey at spinal cervical level C5. The cumulated length of CS axon arbors in the spinal grey matter was not significantly different in the PMG monkey. In the red nucleus, numerous neurons presented large vesicles. We also assessed its motor performances by comparing its capacity to execute a complex reach and grasp behavioral task. The PMG monkey exhibited an increase of reaction time without any modification of other motor parameters, an observation in line with a normal CS tract organisation. Conclusion: In spite of substantial cortical malformations in the frontal and parietal lobes, the PMG monkey exhibits surprisingly normal structure and function of the corticospinal system

Serum RANKL, osteoprotegerin (OPG), and RANKL/OPG ratio in nephrotic children

Receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) play key roles in the pathogenesis of glucocorticoid-induced osteoporosis (GIO). The aim of our study was to determine whether the cumulative glucocorticoid dose (CGCS) in children with idiopathic nephrotic syndrome (INS) has any effect on the concentration of serum RANKL and OPG and the RANKL/OPG ratio. The study population consisted of 90 children with INS, aged 3–20 years, who were treated with GCS. These children were divided into two groups according to the CGCS: low (L) <1 g/kg body weight (BW) and high (H) ≥1 g/kg BW, respectively. The control group (C) consisted of 70 healthy children. RANKL concentration was observed to be significantly higher and OPG significantly lower in INS children than in the reference group: 0.21 (range 0.01–1.36) versus 0.15 (0–1.42) pmol/l (p < 0.05), respectively, and 3.76 (1.01–7.25) versus 3.92 (2.39–10.23) pmol/l (p < 0.05), respectively. The RANKL/OPG ratio was significantly higher in INS children (p < 0.01). The concentration of RANKL, similar to the RANKL/OPG ratio, was significantly higher in Group H children than in Group L children: 0.46 (0.02–1.36 ) versus 0.19 (0.01–1.25) (p < 0.01) and 0.14 (0.01–0.71) versus 0.05 (0.002–0.37) (p < 0.01), respectively. The concentration of OPG was similar in both groups. There was a positive correlation between CGCS and the concentration of sRANKL as well as the RANKL/OPG ratio (in both cases r = 0.33, p < 0.05). Based on these results, we suggest that long-term exposure to GCS results in a dose-dependent increase in serum RANKL concentration and the RANKL/OPG ratio, but not in the level of serum OPG