Nod1-mediated lipolysis promotes diacylglycerol accumulation and successive inflammation via PKCδ-IRAK axis in adipocytes

Chronic inflammation contributes to obesity mediated metabolic disturbances, including insulin resistance. Obesity is associated with altered microbial load in metabolic tissues that can contribute to metabolic inflammation. Different bacterial components such as, LPS, peptidoglycans have been shown to underpin metabolic disturbances through interaction with host innate immune receptors. Activation of Nucleotide-binding oligomerization domain-containing protein 1 (Nod1) with specific peptidoglycan moieties promotes insulin resistance, inflammation and lipolysis in adipocytes. However, it was not clear how Nod1-mediated lipolysis and inflammation is linked. Here, we tested if Nod1-mediated lipolysis caused accumulation of lipid intermediates and promoted cell autonomous inflammation in adipocytes. We showed that Nod1-mediated lipolysis caused accumulation of diacylglycerol (DAG) and activation of PKCδ in 3T3-L1 adipocytes, which was prevented with a Nod1 inhibitor. Nod1-activated PKCδ caused downstream stimulation of IRAK1/4 and was associated with increased expression of proinflammatory cytokines such as, IL-1β, IL-18, IL-6, TNFα and MCP-1. Pharmacological inhibition or siRNA mediated knockdown of IRAK1/4 attenuated Nod1-mediated activation of NF-κB, JNK, and the expression of proinflammatory cytokines. These results reveal that Nod1-mediated lipolysis promoted accumulation of DAG, which engaged PKCδ and IRAK1/4 to augment inflammation in 3T3-L1 adipocytes.     

HOXB13 promotes proliferation,migration, and invasion of glioblastoma through transcriptional upregulation of lncRNA HOXC-AS3

HOXB13 exerts a close relation in several human cancers. This study explored the role of HOXB13 in glioblastoma (GBM), a brain tissue with the highest aggressive rate and mortality in adults. Through microarray and immunohistochemistry analyses, HOXB13 was highly expressed in GBM tissues. Furthermore, we showed that high-level expression of HOXB13 in GBM was associated with worse survival, suggesting that HOXB13 could be a prognostic marker for patients with GBM. GBM cells U87 and U251 overexpressing HOXB13 showed enhanced proliferation, migration, and invasion relative to the control cells, while knockdown of HOXB13 led to decreased cell proliferation, migration, and invasion abilities. In addition, dual-luciferase report assay, chromatin immunoprecipitation assay, and quantitative real-time polymerase chain reaction data showed that HOXB13 directly bound to HOXC-AS3 promoter. HOXC-AS3 was involved in HOXB13-induced proliferation, migration, and invasion of GBM cells. In summary, this study revealed the prognostic potential of HOXB13 in GBM. We believed that HOXB13/HOXC-AS3 signaling axis can be served as therapeutic targets for this highly aggressive cancer.     

Evidence for dynamic resource partitioning between two sympatric reef shark species within the British Indian Ocean Territory

Stable-isotope analyses (δ¹³C, δ¹⁵N and δ³⁴S) of multiple tissues (fin, muscle, red blood cells and plasma), revealed ontogenetic shifts in resource use by grey reef sharks Carcharhinus amblyrhynchos and resource partitioning with silvertip sharks Carcharhinus albimarginatus within the British Indian Ocean Territory marine protected area (MPA). Resource partitioning varied temporally, with C. albimarginatus feeding on more pelagic prey during October to January, potentially attributable to an influx of pelagic prey from outside the MPA at that time. Reef sharks may therefore be affected by processes outside an MPA, even if the sharks do not leave the MPA.     

δ13C and δ15N changes after dietary shift in veliger larvae of the slipper limpet Crepidula fornicata: an experimental evidence

δ¹³C and δ¹⁵N measurements are still poorly conducted in benthic invertebrate larvae. To assess the δ¹³C and δ¹⁵N changes occurring after a dietary shift, experiments were conducted on veliger larvae of Crepidula fornicata fed with two cultured microalgae (Isochrysis galbana and Pavlova lutheri) of known isotopic composition, ¹³C-enriched and ¹⁵N-depleted compared to the initial values of the larvae. Rapid changes in larval δ¹³C and δ¹⁵N were observed after the dietary shift, with an increase in δ¹³C and a decrease in δ¹⁵N. After 19 days of feeding, isotopic equilibrium was still not reached, a period which is close to the duration of the pelagic life of the larvae. This implies that the isotopic composition measured in field-collected larvae might only partly reflect actual larval feeding but also the parental isotopic signature, especially during the early developmental stages. Isotopic measurements in marine invertebrate larvae should thus be interpreted cautiously. In planktonic food web investigations, the study of field-collected larvae of different size/developmental stage may reduce potential misinterpretations.     

Protein kinase Cβ isoform down-regulates the expression of MDR3 P-glycoprotein in human Chang liver cells

The MDR3 protein is a transporter of phosphatidylcholine on the canalicular membrane of human hepatocytes. Previously we showed that the expression of MDR3 mRNA was down-regulated by phorbol 12-myristate 13-acetate (PMA) in human Chang liver cells. In the present study, to elucidate the isoform of protein kinase C (PKC), which influences the level of MDR3 protein, we investigated the effects of PKC-specific inhibitors and antisense oligonucleotides. The level of protein decreased around 50% after treatment for 3–5 days using the dosage of PMA effective against the mRNA expression. The half-life of the MDR3 protein was estimated to be about 5 days. This decrease was antagonized by GF109203X, a non-selective inhibitor of PKCs, and Gö6976, a selective inhibitor for PKCα/β. These inhibitors also suppressed the reduction in MDR3 protein. To specify the isoform of PKC, the cells were treated with antisense oligonucleotide of PKCα or PKCβ. The suppressive effects on MDR3 mRNA of PMA were attenuated in antisense PKCβ-treated cells, but those in antisense PKCα-treated cells were not attenuated. These suggested that PKCβ plays a regulatory role in the expression of MDR3.     

Translocation and conservation of organic nitrogen within the coral-zooxanthella symbiotic system of Acropora pulchra, as demonstrated by dual isotope-labeling techniques

Carbon (C) and nitrogen (N) metabolism of the hermatypic coral Acropora pulchra and its symbiotic algae (zooxanthellae) was investigated using ¹³C and ¹⁵N isotope tracers. A. pulchra was incubated in seawater containing ¹³C-labeled bicarbonate and ¹⁵N-labeled nitrate (NO₃⁻) for 24 h (pulse period), and subsequently ¹³C and ¹⁵N isotopic ratios of the host coral and the zooxanthellae were followed in ¹³C- and ¹⁵N-free seawater for 2 weeks (chase period). Under our experimental condition of NO₃⁻ (12 μM), C and N were absorbed by the coral-algal symbiotic system with the C:N ratio of 23 during the pulse period. Taking account of concentration dependence of NO₃⁻ uptake rates determined by a separate experiment, C:N uptake ratios under supposed in situ NO₃⁻ conditions (< 1.0 μM) would be > 3.0 times higher, if the photosynthetic rate did not change. During the pulse period, more than half of the absorbed ¹³C and ¹⁵N appeared in the host fraction in organic forms. ¹³C:¹⁵N ratio at the end of the pulse period was similar between the host and the algal fraction, suggesting that algal photosynthetic products were translocated to the host. It is also implied that C:N ratios of the translocated products change depending on N availability for the zooxanthellae. During the chase period, atom % excess (APE) ¹⁵N of the zooxanthellae constantly declined, while that of the host slightly increased. Consequently, APE ¹⁵N of the both fractions appeared to approach a common steady state value, suggesting that ¹⁵N was recycled within the coral-algal symbiotic system. As for C, > 86% of C photosynthetically fixed by the zooxanthellae accumulated in the host at the end of the pulse period, and had a turnover time of ca. 20 days for the host C pool during the following chase period. C:N ratios of organic matter newly synthesized with NO₃⁻ exponentially declined and converged into 5.7 and 4.5 for the host and the zooxanthellae, respectively. This suggests that organic compounds of high C:N ratios such as lipids and carbohydrates were selectively consumed more rapidly than those of low C:N ratios such as proteins and nucleic acids.     

松针的化学成分研究

从采自四川夹江的马尾松叶(Pinus massonianaLams.)中分离得到二个化合物,经IR1、H NMR1、3C NMR、2D-NMR、MS等现代波谱技术鉴定为ent-8,13-epoxylabd-14-en-19-oic acid(1)和槲皮素(2)。均为首次从马尾松叶中分离得到。     

Fine Roots vs. Needles: A Comparison of 13C and 15N Dynamics in a Ponderosa Pine Forest Soil

Plant allocation patterns may affect soil C and N storage due to differences in litter quality and the depth of plant C and N inputs into the soil. We studied the dynamics of dual-labeled (¹³C/¹⁵N) Pinus ponderosa needles and fine roots placed at two soil depths (O and A horizon) in a temperate conifer forest soil during 2 y. Input of C as fine roots resulted in much more C retained in soil (70.5 ± 2.2% of applied) compared with needle C (42.9 ± 1.3% of applied) after 1.5 y. Needles showed faster mass loss, rates of soil ¹³CO₂ efflux, and more ¹⁵N immobilized into microbial biomass than did fine roots. The larger proportion of labile C compounds initially present in needles (17% more needle C was water soluble than in fine roots) likely contributed to its shorter C residence time and greater degree of transformation in the soil. A double exponential decay function best described the rate of ¹³C loss, with a smaller initial pulse of C loss from fine roots (S₁k₁) and a slower decay rate of the recalcitrant C pool for fine roots (0.03 y⁻¹) compared with (0.19 y⁻¹) for needles. Soil ¹³C respiration, representing heterotrophic respiration of litter C, was much more seasonal from the O horizon than from the A. However, offsetting seasonal patterns in ¹³C dynamics in the O horizon resulted in no net effect of soil depth on total ¹³C retention in the soil after 1.5 y for either litter. Almost 90% of applied litter N was retained in the soil after 1.5 y, independent of litter quality or soil depth. Very small amounts of ¹³C or ¹⁵N (<3% of applied) moved to the horizon above or below the placement depth (i.e., O to A or A to O). Our results suggest that plant allocation belowground to fine roots results in more C retained and less N mineralized compared with allocation aboveground to needles, primarily due to litter quality differences.