The protective effect of WKYMVm peptide on inflammatory osteolysis through regulating NF‐κB and CD9/gp130/STAT3 signalling pathway

The balance between bone formation and bone resorption is closely related to bone homeostasis. Osteoclasts, originating from the monocyte/macrophage lineage, are the only cell type possessing bone resorption ability. Osteoclast overactivity is thought to be the major reason underlying osteoclast‐related osteolytic problems, such as Paget's disease, aseptic loosening of prostheses and inflammatory osteolysis; therefore, disruption of osteoclastogenesis is considered a crucial treatment option for these issues. WKYMVm, a synthetic peptide, which is a potent FPR2 agonist, exerts an immunoregulatory effect. This peptide inhibits the production of inflammatory cytokines, such as (IL)‐1β and TNF‐α, thus regulating inflammation. However, there are only few reports on the role of WKYMVm and FPR2 in osteoclast cytology. In the current study, we found that WKYMVm negatively regulates RANKL‐ and lipopolysaccharide (LPS)‐induced osteoclast differentiation and maturation in vitro and alleviates LPS‐induced osteolysis in animal models. WKYMVm down‐regulated the expression of osteoclast marker genes and resorption activity. Furthermore, WKYMVm inhibited osteoclastogenesis directly through reducing the phosphorylation of STAT3 and NF‐kB and indirectly through the CD9/gp130/STAT3 pathway. In conclusion, our findings demonstrated the potential medicinal value of WKYMVm for the treatment of inflammatory osteolysis.     

PGC-1 Coactivators Regulate MITF and the Tanning Response

1. Download : Download high-res image (175KB)
2. Download : Download full-size image

Highlights? PGC-1 induces pigment formation in melanocytes ? PGC-1s activate expression of MITF ? α-MSH induces PGC-1s, which are required for induction of melanogenic genes ? eQTLs in human PGC-1β are associated with tanning ability and melanoma protection     

Association between a rare novel TP53 variant (rs78378222) and melanoma,squamous cell carcinoma of head and neck and lung cancer susceptibility in non‐Hispanic Whites

Recently, several studies have investigated the association between a newly reported rare functional single nucleotide polymorphism (SNP) in TP53 (rs78378222) and cancer risk, but generated inconsistent findings. The present study further investigated this association with risk of melanoma, squamous cell carcinoma of head and neck (SCCHN) and lung cancer. Using volunteers of non‐Hispanic Whites recruited for three large case–control studies, we genotyped the TP53 rs78378222 SNP in 1329 patients with melanoma, 1096 with SCCHN, 1013 with lung cancer and 3000 cancer‐free controls. Overall, we did not observe any variant homozygotes in this study population, nor significant associations between the TP53 rs78378222AC genotype or C allele and risk for melanoma (P = 0.680 and 0.682 respectively) and lung cancer (P = 0.379 and 0.382 respectively), but a protection against SCCHN (P = 0.008 and 0.008 respectively), compared with the AA genotype or A allele. An additional meta‐analysis including 19,423 cancer patients and 54,050 controls did not support such a risk association either. Our studies did not provide statistical evidence of an association between this rare TP53 variant and increased risk of melanoma, nor of lung cancer, but a possible protection against SCCHN.     

Negative Refraction and Focusing of Photonic Crystals with Graded Negative Index in Visible Regime

In this paper, we designed a hexagonal lattice photonic crystal (PC) which presents negative refraction behavior in the broadband visible region. By varying the PC parameters, a graded index PC was obtained for the purpose of focusing a plane wave with large transmission. Finite-difference and time-domain algorithm-based numerical calculation was adopted to demonstrate the negative refraction and analyze the focusing effect. Calculation results demonstrate that the designed PCs have good focusing property together with large transmission. The proposed structures provide an approach for designing the negative refraction-based imaging systems.     

Obesity-related genetic variants, human pigmentation, and risk of melanoma

Previous biological studies showed evidence of a genetic link between obesity and pigmentation in both animal models and humans. Our study investigated the individual and joint associations between obesity-related single nucleotide polymorphisms (SNPs) and both human pigmentation and risk of melanoma. Eight obesity-related SNPs in the FTO, MAP2K5, NEGR1, FLJ35779, ETV5, CADM2, and NUDT3 genes were nominally significantly associated with hair color among 5,876 individuals of European ancestry. The genetic score combining 35 independent obesity-risk loci was significantly associated with darker hair color (beta-coefficient per ten alleles = 0.12, P value = 4 × 10^?5). However, single SNPs or genetic scores showed non-significant association with tanning ability. We further examined the SNPs at the FTO locus for their associations with pigmentation and risk of melanoma. Among the 783 SNPs in the FTO gene with imputation R ² quality metric >0.8 using the 1,000 genome data set, ten and three independent SNPs were significantly associated with hair color and tanning ability respectively. Moreover, five independent FTO SNPs showed nominally significant association with risk of melanoma in 1,804 cases and 1,026 controls. But none of them was associated with obesity or in linkage disequilibrium with obesity-related variants. FTO locus may confer variation in human pigmentation and risk of melanoma, which may be independent of its effect on obesity.     

鳊鱼和宽鳍鱲幼鱼流速选择与运动能量代谢特征的关联

为考察喜好激流环境的宽鳍鱲(Zacco platypus)和喜好缓流环境的鳊鱼(Parabramis pekinensis)的最适游泳速度和流速选择的关联以及运动能量代谢特征对流速选择的影响,在(25±0.5)℃条件下将实验鱼(n=13×2)单尾分别置于梯度流速选择仪(设定流速范围为18.6—102.7 cm/s,等距离划分为5个流速区域)中获取视频资料,采用Ethovision XT19软件分析视频资料并计算两种实验鱼在5个流速区域的平均停留时间百分比(P_t)和平均出入频率百分比(Pf);另外,使用游泳代谢仪测定两种实验鱼的临界游泳速度(U_(crit))和不同游泳速度下的运动耗氧率(M_(O2)),并计算出不同速度下单位位移耗能(COT)、最适游泳速度(U_(opt))、静止耗氧率(RMR)和净单位位移耗能(COTnet)。结果显示:鳊鱼的U_(crit)和RMR均显著小于宽鳍鱲(P0.05),但二者的最大耗氧率(MMR)无显著差异;随游泳速度的增加,两种实验鱼的M_(O2)均显著上升,尽管在较低游泳速度下,鳊鱼的M_(O2)和COT均小于宽鳍鱲,但在高游泳速度下则相反;两种实验鱼的U_(opt)分别为(6.20±1.29)体长(BL)/s和(11.56±1.57)BL/s,鳊鱼显著小于宽鳍鱲;两种实验鱼的COTnet随着游泳速度增加差异逐渐增大,鳊鱼显著高于宽鳍鱲(P0.05);两种实验鱼在最低流速区域(18.6—23.8 cm/s)的P_t和Pf显著大于其他速度区域(P0.05),由此可见两种实验鱼的偏好游泳速度(U_(perf))等于或小于(18.6—23.8 cm/s),然而鳊鱼在最低速度区域P_t和Pf均显著大于且在较高速度区域的P_t和Pf则均显著小于宽鳍鱲(P0.05)。结果表明:有别于过往研究的是两种实验鱼的U_(perf)均与U_(opt)偏离;在激流环境中生存的宽鳍鱲更加偏好较高的水流速度,生境水流对实验鱼的水流速度选择特征存在显著影响,这种影响的主要能量学机制与鱼类的运动能量效率有关。     

Biodiversity and water quality variations in constructed wetland of Yongding River system

This research was carried on in constructed wetlands of Guan-Ting Reservoir, Beijing, China, from 2004 to 2005. The phytoplankon community was composed of 8 divisions (94 species, including genus and varieties) and the average cell density was 980.93× 10⁴ cells per liter. The dominant divisions were Chlorophyta (36.8%), Bacillariophyta (31.0%) and Cyanophyta (23.4%). The removal rate of phytoplankton density was 72.7%. There was a positive linear correlation between phytoplankon density and total phosphorus. Here, 7 families (13 species) of aquatic vasular plants were found, which constituted emerging and submerging macrophyte communities. In the wetland system, the zooplankton community consisted of Protozoa, Rotifera, Cladocera and Copepoda (70 species). The average density was 4883 individuals per liter. Protozoan and Rotifera were the dominant groups and the removal rate of their density was 81.9%. The correlation between zooplankton and phytoplankton presented a quadratic curve. Also, the zoobenthos community contained Olisochaeta, Uniramia, Crustacea and Mollusca (15 species). The average density was 5670 individuals per m² (62.3% was Uniramia) and the removal rate of their density was 92.4 %. The wetland system reduced COD_Mn, BOD₅, TN, NH_3-N, NO_3-N, TP (total phosphor), PO_4-P and SS in the water of Yong Ding River at 52.9%–99.1%.     

Rapid assessment of repair of ultraviolet DNA damage with a modified host-cell reactivation assay using a luciferase reporter gene and correlation with polymorphisms of DNA repair genes in normal human lymphocytes

As DNA repair plays an important role in genetic susceptibility to cancer, assessment of the DNA repair phenotype is critical for molecular epidemiological studies of cancer. In this report, we compared use of the luciferase (luc) reporter gene in a host-cell reactivation (HCR) (LUC) assay of repair of ultraviolet (UV) damage to DNA to use of the chloramphenicol (cat) gene-based HCR (CAT) assay we used previously for case-control studies. We performed both the assays on cryopreserved lymphocytes from 102 healthy non-Hispanic white subjects. There was a close correlation between DNA repair capacity (DRC) as measured by the LUC and CAT assays. Although these two assays had similar variation, the LUC assay was faster and more sensitive. We also analyzed the relationship between DRC and the subjects' previously determined genotypes for four polymorphisms of two nucleotide-excision repair (NER) genes (in intron 9 of xeroderma pigmentosum (XP) C and exons 6, 10 and 23 of XPD) and one polymorphism of a base-excision repair gene in exon 10 of X-ray complementing group 1 (XRCC1). The DRC was significantly lower in subjects homozygous for one or more polymorphisms of the two NER genes than in subjects with other genotypes (P=0.010). In contrast, the polymorphic XRCC1 allele had no significant effect on DRC. These results suggest that the post-UV LUC assay measures NER phenotype and that polymorphisms of XPC and XPD genes modulate DRC. For population studies of the DNA repair phenotype, many samples need to be evaluated, and so the LUC assay has several advantages over the CAT assay: the LUC assay was more sensitive, had less variation, was not radioactive, was easier to perform, and required fewer cryopreserved cells. These features make the LUC-based HCR assay suitable for molecular epidemiological studies.     

The Endogenous and Cell Cycle-dependent Phosphorylation of tau Protein in Living Cells: Implications for Alzheimer’s Disease

In Alzheimer’s disease the neuronal microtubule-associated protein tau becomes highly phosphorylated, loses its binding properties, and aggregates into paired helical filaments. There is increasing evidence that the events leading to this hyperphosphorylation are related to mitotic mechanisms. Hence, we have analyzed the physiological phosphorylation of endogenous tau protein in metabolically labeled human neuroblastoma cells and in Chinese hamster ovary cells stably transfected with tau. In nonsynchronized cultures the phosphorylation pattern was remarkably similar in both cell lines, suggesting a similar balance of kinases and phosphatases with respect to tau. Using phosphopeptide mapping and sequencing we identified 17 phosphorylation sites comprising 80–90% of the total phosphate incorporated. Most of these are in SP or TP motifs, except S214 and S262. Since phosphorylation of microtubule-associated proteins increases during mitosis, concomitant with increased microtubule dynamics, we analyzed cells mitotically arrested with nocodazole. This revealed that S214 is a prominent phosphorylation site in metaphase, but not in interphase. Phosphorylation of this residue strongly decreases the tau–microtubule interaction in vitro, suppresses microtubule assembly, and may be a key factor in the observed detachment of tau from microtubules during mitosis. Since S214 is also phosphorylated in Alzheimer’s disease tau, our results support the view that reactivation of the cell cycle machinery is involved in tau hyperphosphorylation.