The role of p21-activated kinases in hepatocellular carcinoma metastasis

The p21-activated kinases (PAKs) are downstream effectors of the Rho family small GTPases as well as a wide variety of mitogenic factors and have been implicated in cancer formation, development and metastasis. PAKs phosphorylate a wide spectrum of substrates to mediate extracellular signals and regulate cytoskeletal remodeling, cell motility and survival. In this review, we aim to summarize the findings regarding the oncogenic role and the underlying mechanisms of PAKs signaling in various cancers, and in particular highlight the prime importance of PAKs in hepatocellular carcinoma (HCC) progression and metastasis. Recent studies exploring the potential therapeutic application of PAK inhibitors will also be discussed.     

紫羊茅重金属抗性和敏感品种中类金属硫蛋白基因的鉴定及表达初探

重金属对生命机体的作用具有双重性。一方面,作为多数辅酶的辅助因子对细胞的正常代谢必不可少;另一方面,当重金属超过一定的浓度时对细胞有较大的毒性。在长期的进化过程中,生物可能形成一种调节细胞内重金属浓度的机制。这种机制在动物和真菌中被认为同金属硫蛋白(metallothionein,MT)的作用密切相关。植物中也存在类似的与重金属结合的低分子量蛋白(heavy metal binding pep-tide)。最近对拟南芥菜和水稻中类金属硫蛋白(MT-like)基因的研究证实其作用与动物MT相似。紫羊茅品种“Merlin”是一种从锌铅矿区的重金属污染地采集的单子叶草种,对镉和铜的抗性都较高,分别达到50mg/L和30mg/L,而5mg/L Cd~(2 )或2mg/L Cu~(2 )便可抑制敏感品种“S59”的正常生长。目前     

Modulation of the K(v)4.3 channel by syntaxin 1A

The SNARE protein syntaxin 1A (Syn1A) is known to inhibit delayed rectifier K(+) channels of the K(v)1 and K(v)2 families with heterogeneous effects on their gating properties. In this study, we explored whether Syn1A could directly modulate K(v)4.3, a rapidly inactivating K(v) channel with important roles in neuroendocrine cells and cardiac myocytes. Immunoprecipitation studies in HEK293 cells coexpressing Syn1A and K(v)4.3 revealed a direct interaction with increased trafficking to the plasma membrane without a change in channel synthesis. Paradoxically, Syn1A inhibited K(v)4.3 current density. In particular, Syn1A produced a left-shift in steady-state inactivation of K(v)4.3 without affecting either voltage dependence of activation or gating kinetics, a pattern distinct from other K(v) channels. Combined with our previous reports, our results further verify the notion that the mechanisms involved in Syn1A-K(v) interactions vary significantly between K(v) channels, thus providing a wide scope for Syn1A modulation of exocytosis and membrane excitability.     

Scx-Transduced Tendon-Derived Stem Cells (TDSCs) Promoted Better Tendon Repair Compared to Mock-Transduced Cells in a Rat Patellar Tendon Window Injury Model

We hypothesized that the transplantation of Scx-transduced tendon-derived stem cells (TDSCs) promoted better tendon repair compared to the transplantation of mock-transduced cells. This study thus aimed to investigate the effect of Scx transduction on the expression of lineage markers in TDSCs and the effect of the resulting cell line in the promotion of tendon repair. Rat non-GFP or GFP-TDSCs were transduced with Scx or empty lentiviral vector (Mock) and selected by blasticidin. The mRNA expressions of Scx and different lineage markers were examined by qRT-PCR. The effect of the transplantation of GFP-TDSC-Scx on tendon repair was then tested in a rat unilateral patellar tendon window injury model. The transplantation of GFP-TDSC-Mock and scaffold-only served as controls. At week 2, 4 and 8 post-transplantation, the repaired patellar tendon was harvested for ex vivo fluorescent imaging, vivaCT imaging, histology, immunohistochemistry and biomechanical test. GFP-TDSC-Scx consistently showed higher expressions of most of tendon- and cartilage- related markers compared to the GFP-TDSC-Mock. However, the effect of Scx transduction on the expressions of bone-related markers was inconclusive. The transplanted GFP-TDSCs could be detected in the window wound at week 2 but not at week 4. Ectopic mineralization was detected in some samples at week 8 but there was no difference among different groups. The GFP-TDSC-Scx group only statistically significantly improved tendon repair histologically and biomechanically compared to the Scaffold-only group and the GFP-TDSC-Mock group at the early stage of tendon repair. There was significant higher expression of collagen type I in the window wound in the GFP-TDSC-Scx group compared to the other two groups at week 2. The transplantation of GFP-TDSC-Scx promoted healing at the early stage of tendon repair in a rat patellar tendon window injury model.     

Coding and potential regulatory sequences of a cluster of chorion genes in Drosophila melanogaster

We have characterized at the nucleotide level a 4.8-kilobase pair segment of the third chromosome of Droophila melanogaster, which contains a cluster of three chorion genes, s 18-1, s 15-1 and s 19-1. These genes are tandemly oriented and share the same basic organization: a small and a large exon separated by a short intron in the signal peptide region. In the coding region, limited similarities at the DNA and protein level suggest a common but distant evolutionary origin. The flanking sequences were searched for elements that might be involved in controlling the tissue-specific and temporally regulated expression and the selective amplification of the chorion genes. A good candidate for a cis-regulatory element is the hexamer, TCACGT, which is found in all three genes in a highly significant position, 23 to 27 nucleotides upstream of the TATA-box, accompanied by additional, less exact similarities. Palindromes and short inverted repeats that are found in the vicinity of their complement are non-uniformly distributed: they are most concentrated in the 3 flanking part of all three genes, in and near regions of unusually high A and T content. The highest number of dyad symmetries, remiiscent of sequences that function as viral replication origins, is found associated with the T- and A-rich regions between genes s18-1 and s15-1.     

The small-subunit ribosomal RNA gene sequences from the hypotrichous ciliates Oxytricha nova and Stylonychia pustulata

We have determined the complete nucleotide sequence of the small- subunit ribosomal RNA genes for the ciliate protozoans Stylonychia pustulata and Oxytricha nova. The sequences are homologous and sufficiently similar that these organisms must be closely related. In a phylogeny inferred from comparisons of several eukaryotic small-subunit ribosomal RNAs, the divergence of the ciliates from the eukaryotic line of descent is seen to coincide with the radiation of the plants, the animals, and the fungi. This radiation is preceded by the divergence of the slime mold, Dictyostelium discoideum.      

Nickel Allergy Is a Risk Factor for Endometriosis: An 11-Year Population-Based Nested Case-Control Study

BackgroundA cross-sectional study has reported that nickel allergy is associated with endometriosis. However, causal studies of this association are limited.ObjectiveThe objective of this study was to compare the prevalence of nickel allergy in women with and without endometriosis.MethodsWe used a National Health Insurance Service (NHIS) sample cohort dataset that included approximately 1 million individuals from South Korea; the data were obtained between January 01, 2002, and December 31, 2013. We selected the endometriosis group according to diagnosis code (N80.X), surgery codes, and drug codes during the years 2009~2013. The controls were randomly matched to the endometriosis patients at a ratio of 4:1 by age and socioeconomic status. Patients with nickel allergy were defined in the cohort dataset as those with a simultaneous diagnosis code (L23.0) and patch test code during 2002~2008.ResultsIn total, 4,985 women were selected from the NHIS cohort database and divided into an endometriosis group (997 women) and a control group (3,988 women). The number of patients with nickel allergy in the endometriosis group was eight (0.8%), and that in the control group was thirteen (0.3%). After adjustment for age and socioeconomic status, the rate of nickel allergy in was higher in the endometriosis group than in the control group [odds ratio: 2.474; 95% confidence interval: 1.023~5.988; p = 0.044].ConclusionsWe found that nickel allergy is a risk factor for endometriosis.