Human T-cell leukemia virus type 2 Tax protein induces interleukin 2-independent growth in a T-cell line

BACKGROUND: While human T-cell leukemia virus type 1 (HTLV-1) is a causative agent of adult T-cell leukemia, HTLV type 2 (HTLV-2) is not associated with this malignancy. Accumulating evidence suggests that Tax, a transforming protein of HTLV-1 or HTLV-2, plays a crucial role in the distinctive pathogenesis of these two infections. We herein examined whether Tax2 by itself has a growth promoting activity in a mouse T-cell line CTLL-2, and compared the activity with that of Tax1. RESULTS: We found that Tax2 converts the cell growth of CTLL-2 from an interleukin(IL)-2-dependent growth into an independent one. Cyclosporine A, an inhibitor of transcription factor NFAT, inhibited the growth of two out of four Tax2-transformed CTLL-2 cells, but it had little effect on two Tax1-transformed cells. While the HTLV-2-transformed human T-cell lines produce a significant amount of IL-2, Tax2-transformed CTLL-2 cells only produced a minimal amount of IL-2. These results thus suggest that NFAT-inducible gene(s) other than IL-2 play a role in the cell growth of Tax2-transformed CTLL-2 cells. CONCLUSION: These results show that HTLV-2 Tax2 by itself has a growth promoting activity toward a T-cell line CTLL-2, and the CTLL-2 assay used in this study may therefore be a useful tool for comparing the activity of Tax2 with that of Tax1 in T-cells, thereby elucidating the mechanism of HTLV-1 specific leukemogenesis

C. elegans PlexinA PLX-1 mediates a cell contact-dependent stop signal in vulval precursor cells

AbstractPLX-1 is a PlexinA transmembrane protein in Caenorhabditis elegans, and the transmembrane-type semaphorin, SMP-1, is a ligand for PLX-1. The SMP-1/PLX-1 system has been shown to be necessary for proper epidermal morphogenesis in the male tail and seam cells. Here, we show that the SMP-1/PLX-1 system also regulates vulval morphogenesis. In plx-1 and smp-1 mutants, hermaphrodites sometimes exhibit a protruding vulva or multiple vulva-like protrusions. Throughout the vulval development of plx-1 and smp-1 mutants, the arrangement of vulval cells is often disrupted. In the initial step of vulval morphogenesis, vulval precursor cells (VPCs) are generated normally but are subsequently arranged abnormally in mutants. Continuous observation revealed that plx-1 VPC fails to terminate longitudinal extension after making contact with neighbor VPCs. The arrangement defects of VPCs in plx-1 and smp-1 mutants are rescued by expressing the respective cDNA in VPCs. plx-1::egfp and smp-1::egfp transgenes are both expressed in all vulval cells, including VPCs, throughout vulval development. We propose that the SMP-1/PLX-1 system is responsible for a cell contact-mediated stop signal for VPC extension. Analyses using cell fate-specific markers showed that the arrangement defects of VPCs also affect cell fate specification and cell lineages, but in a relatively small fraction of plx-1 mutants

Identification of a novel motif responsible for the distinctive transforming activity of human T-cell leukemia virus (HTLV) type 1 Tax1 protein from HTLV-2 Tax2

<p>Abstract</p> <p>Background</p> <p>Human T-cell leukemia virus type 1 (HTLV-1) is a causative agent of adult T-cell leukemia (ATL), whereas its relative HTLV-2 is not associated with any malignancies including ATL. HTLV-1 Tax1 transformed a T-cell line from interleukin (IL)-2-dependent growth to IL-2-independent growth, with an activity that was much more potent in comparison to HTLV-2 Tax2. This distinction was mediated by at least two Tax1 specific functions, an interaction with host cellular factors through the PDZ domain binding motif (PBM) and the activation of NF-kappaB2 (NF-κB2)/p100.</p> <p>Results</p> <p>Using a series of Tax1 chimeric proteins with Tax2, we found that amino acids 225-232 of Tax1, the Tax1(225-232) region, was essential for the activation of NF-κB2 as well as for the high transforming activity. The strict amino acid conservation of Tax1(225-232) among HTLV-1 and simian T-cell leukemia virus type 1 (STLV-1), but not HTLV-2 and STLV-2, indicates that function(s) through the Tax1(225-232) region are biologically significant. Interestingly, another HTLV-1 relative, HTLV-3, has a PBM, but does not conserve the Tax1(225-232) motif in Tax3, thus indicating that these two motifs classify the three HTLVs into the separate groups.</p> <p>Conclusion</p> <p>These results suggest that the combinatory functions through Tax1(225-232) and PBM play crucial roles in the distinct biological properties of the three HTLVs, perhaps also including their pathogenesis.</p

Relationship between Orthodontic Expertise and Perception of Need for Orthodontic Treatment for Mandibular Protrusion in Japan

The aims of this study were to investigate how the Peer Assessment Rating (PAR index) predicts the perceived need for orthodontic treatment of mandibular protrusion in Japanese subjects, and to elucidate whether the perceived need for treatment was affected by the ratersʼ orthodontic expertise. The subjects were 110 dental students and 32 orthodontists. We showed them casts of 10 untreated mandibular protrusion cases and gave them a questionnaire in which they had to describe their perceptions of the orthodontic treatment needs using a 10-point visual analog scale (VAS). The PAR index was used for cast evaluation. The PAR index scores showed significant correlations with the VAS scores. In casts with a low PAR score, there were no differences in the VAS scores between orthodontists and students. In casts with a PAR score greater than 23, the orthodontists perceived a significantly greater treatment need than did the students;for scores of 22, 28, and 29, students who had received orthodontic treatment themselves were more likely to perceive the treatment need. The PAR index is a good clinical predictor for assessing the perceived treatment needs for mandibular protrusion. Perception of the need for orthodontic treatment for mandibular protrusion depended on the degree of orthodontic expertise in Japanese subjects

Dense Molecular Clumps associated with the LMC Supergiant Shells LMC 4 \& LMC 5

We investigate the effects of Supergiant Shells (SGSs) and their interaction on dense molecular clumps by observing the Large Magellanic Cloud (LMC) star forming regions N48 and N49, which are located between two SGSs, LMC 4 and LMC 5. $^{12}$CO ($J$=3-2, 1-0) and $^{13}$CO ($J$=1-0) observations with the ASTE and Mopra telescopes have been carried out towards these regions. A clumpy distribution of dense molecular clumps is revealed with 7 pc spatial resolution. Large velocity gradient analysis shows that the molecular hydrogen densities ($n({\rm H}_2)$) of the clumps are distributed from low to high density ($10^3$-$10^5$ cm$^{-3}$) and their kinetic temperatures ($T_{\rm kin}$) are typically high (greater than $50$ K). These clumps seem to be in the early stages of star formation, as also indicated from the distribution of H$\alpha$, young stellar object candidates, and IR emission. We found that the N48 region is located in the high column density HI envelope at the interface of the two SGSs and the star formation is relatively evolved, whereas the N49 region is associated with LMC 5 alone and the star formation is quiet. The clumps in the N48 region typically show high $n({\rm H}_2)$ and $T_{\rm kin}$, which are as dense and warm as the clumps in LMC massive cluster-forming areas (30 Dor, N159). These results suggest that the large-scale structure of the SGSs, especially the interaction of two SGSs, works efficiently on the formation of dense molecular clumps and stars.Comment: 26 pages, 7 tables, 16 figure