Hyphal tip growth and nuclear migration

Recent molecular and cytological studies have greatly advanced our understanding of hyphal tip growth and nuclear migration in filamentous fungi. Mutants involved in various aspects of hyphal tip growth have been isolated. Genes involved in nuclear migration continue to be identified, including putative regulators. The role of microtubules and microtubule motor proteins in hyphal tip growth has also been studied.     

Solution structure of BmKalphaIT01, an alpha-insect toxin from the venom of the Chinese scorpion Buthus martensii Karsch

The solution structure of an alpha-insect toxin from Buthus martensii Karsch, BmKalphaIT01, has been determined by two-dimensional NMR spectroscopy and molecular modeling techniques. Combining the sequence homology comparison and toxicity bioassays, BmKalphaIT01 has been suggested to be a natural mutant of alpha-insect toxins and so can serve as a tool to study the relationship of structure-function among this group of toxins. The overall structure of BmKalphaIT01 shares a common core structure consisting of an alpha-helix packed against a three-stranded antiparallel beta-sheet, which exhibits distinctive local conformations within the loops connecting these secondary structure elements. The solution structure of BmKalphaIT01 features a non-proline cis peptide bond between Asn9 and Tyr10, which is proposed to mediate the spatial closing of the five-residue turn (Gln8-Cys12) and the C-terminal segment (Arg58-His64) to form the NC domain and confer the toxin insect-specific bioactivity. Conformational heterogeneity is observed in the solution of BmKalphaIT01 and could be attributed to the cis-trans isomerization of the peptide bond between residues 9 and 10. The minor conformation of BmKalphaIT01 with a trans peptide bond between Asn9 and Tyr10 may be responsible for its moderate bioactivity against mammals. The cis-trans isomerization of the peptide bond between residues 9 and 10 may be the structural basis of dual pharmacological activities of alpha-insect and alpha-like scorpion toxins, which is supported by the fact that conformational heterogeneity occurs in the solution structures of LqhalphaIT, LqqIII, and LqhIII and by comparison of the solution structure of BmKalphaIT01 with those of some relevant alpha-type toxins.     

rtcisE2F promotes the self-renewal and metastasis of liver tumor-initiating cells via N6-methyladenosine-dependent E2F3/E2F6 mRNA stability

Liver cancer is highly heterogeneous,and the tumor tissue harbors a variety of cell types.Liver tumor initiating cells(TICs) well contribute to tumor heterogeneity and account for tumor initiation and metastasis,but the molecular mechanisms of liver TIC self-renewal are elusive.Here,we identified a functional read-through rt-circRNA,termed rtcisE2 F,that is highly expressed in liver cancer and liver TICs.rtcisE2 F plays essential roles in the self-renewal and activities of liver TICs.rtcisE2 F t...     

A population-based LD map of the human chromosome 6p

The recent publication of the complete sequence of human chromosome 6 provides a platform from which to investigate genomic sequence variation. We report here a detailed linkage disequilibrium (LD) pattern map across the entire human chromosome 6p by using a set of 1152 single nucleotide polymorphisms (SNPs) in a population of 198 Singaporean Chinese, with 326 SNPs focused in the major histocompatibility complex (MHC) region. Our analysis shows some unexpectedly high segments of strong LD in a 10-Mb region that includes the extremely polymorphic and gene-rich MHC loci and many non-MHC genes. These include the telomeric peri-MHC region that harbors olfactory receptors, histones and zinc finger clusters, and the centromeric peri-MHC region that contains several unknown open reading frames. The data also help refine a human–mouse synteny break in the region between 28.6 and 29.4 Mb. The population-based LD map presented here will provide an essential resource for understanding the genomic sequence variation of chromosome 6p and LD mapping of disease genes of complex genetic traits. Electronic supplementary material Electronic supplementary material is available for this article at and accessible for authorised users. H. Yu and J.-M. Chia should be regarded as joint first authors.     

Alkaloids from Portulaca oleracea L

Five alkaloids (oleraceins A, B, C, D and E) were isolated from Portulaca oleracea L., and their structures determined by spectroscopic methods as 5-hydroxy-1-p-coumaric acyl-2,3-dihydro-1H-indole-2-carboxylic acid-6-O-beta-D-glucopyranoside, 5-hydroxy-1-ferulic acyl-2,3-dihydro-1H-indole-2-carboxylic acid-6-O-beta-D-glucopyranoside, 5-hydroxy-1-(p-coumaric acyl-7'-O-beta-D-glucopyranose)-2,3-dihydro-1H-indole-2-carboxylic acid-6-O-beta-D-glucopyranoside, 5-hydroxy-1-(ferulic acyl-7'-O-beta-D-glucopyranose)-2,3-dihydro-1H-indole-2-carboxylic acid-6-O-beta-D-glucopyranoside and 8,9-dihydroxy-1,5,6,10b-tetrahydro-2H-pyrrolo[2,1-a]isoquinolin-3-one, respectively.     

T helper cell related interleukins and the angiographic morphology in unstable angina

Angiographically visible complex lesions, associated with disrupted plaques and intraluminal thrombus, are more common in unstable angina (UA). The aim of our study was to evaluate the relationship between the complex lesions and the T helper cells related Interleukins (IL). We analyzed the concentrations of IL-10, IL-12, IL-18 using ELISA and that of hsCRP using Latex particle enhanced Immunoturbidimetry in 50 patients of UA. Thirty-one of these patients had complex lesions and 19 had simple lesions as visible during coronary angiography. We further compared them with 30 control subjects having no evidence of coronary artery diseases. The levels of IL-12 in patients having complex lesions tended to be higher than in those having simple lesions and levels of IL-10 tended to be lower in the former than the latter, but the differences were not statistically significant. The patients with complex lesions showed significantly higher concentrations of IL-18 as compared to those having simple lesions. Furthermore, IL-18 was found to be independent predictor for the complex lesion morphology in UA patients. These findings suggest that disrupted plaques and intraluminal thrombus, angiographically visible as complex lesions are associated with increased concentrations of T helper 1 cell related interleukins, mainly IL-18, and IL-18 being a possible bio-marker for risk stratification in UA.     

Mitotic requirement for aurora A kinase is bypassed in the absence of aurora B kinase

We investigated why treatment of cells with dual aurora A and B kinase inhibitors produces phenotypes identical to inactivation of aurora B. We found that dual aurora kinase inhibitors in fact potently inhibit cellular activities of both kinases, indicating that inactivation of aurora B bypasses aurora A in mitosis. RNAi experiments further established that inactivation of aurora B indeed bypasses the requirement for aurora A and leads to polyploidy. Inactivation of aurora A activates checkpoint kinase BubR1 in an aurora B-dependent manner. Our results thus show that aurora B is responsible for mitotic arrest in the absence of aurora A.     

hNRAGE, a human neurotrophin receptor interacting MAGE homologue, regulates p53 transcriptional activity and inhibits cell proliferation

hNRAGE, a neurotrophin receptor p75 interacting MAGE homologue, is cloned from a human placenta cDNA library. hNRAGE can inhibit the colony formation of and arrest cell proliferation at the G1/S and G2/M stages in hNRAGE overexpressing cells. Interestingly, hNRAGE also increases the p53 protein level as well as its phosphorylation (Ser392). Further studies demonstrated that hNRAGE does not affect the proliferation of mouse p53-/- embryonic fibroblasts, suggesting that p53 function is required for hNRAGE induced cell cycle arrest. Moreover, the cell cycle inhibiting protein p21(WAF) is induced by hNRAGE in a p53 dependent manner. The data provide original evidence that hNRAGE arrests cell growth through a p53 dependent pathway.     

The salt bridge of calcineurin is important for transferring the effect of CNB binding to CNA

Calcineurin (CN) is a heterodimer consisting of a catalytic subunit (CNA) and a regulatory subunit (CNB). The crystal structure shows that three residues or regions of CNA are mainly responsible for the interaction with CNB: the CNB binding helix (BBH), the N-terminus, and Glu53 that forms a salt bridge with Lys134 of CNB. In this report, we try to find the role that the salt bridge plays in the interaction between CNA and CNB. We found that mutation of Glu53 greatly reduced its responsiveness to CNB in the phosphatase assay and also that mutation of Lys134 of CNB affected its ability to activate the phosphatase activity of CNA. Structural analysis showed that disruption of the salt bridge affected the compact association of CNA and CNB. Thus, the salt bridge appears to help to stabilize CN and transfer the effects of CNB binding to CNA to activate its phosphatase activity.