Tyrosine phosphorylation of the CrkII adaptor protein modulates cell migration

CrkII belongs to a family of adaptor proteins that become tyrosine phosphorylated after various stimuli. We examined the role of CrkII tyrosine phosphorylation in fibronectin-induced cell migration. Overexpression of CrkII inhibited dephosphorylation of focal adhesion components such as p130 Crk-associated substrate (p130cas) and paxillin by protein tyrosine phosphatase 1B (PTP1B). Tyrosine-phosphorylated CrkII was dephosphorylated by PTP1B both in vitro and in vivo, showing for the first time that PTP1B directly dephosphorylates CrkII. A CrkII mutant in which tyrosine residue 221 was substituted by phenylalanine (CrkII-Y221F) could not be tyrosine phosphorylated, and it showed significantly increased binding to p130cas and paxillin. Enhanced binding of CrkII to p130cas has been reported to promote cell migration. Nonphosphorylated CrkII-Y221F promoted HT1080 cell migration on fibronectin, whereas wild-type CrkII did not at moderate expression levels. Moreover, co-expression of CrkII and PTP1B promoted HT1080 cell migration on fibronectin and retained tyrosine phosphorylation and binding of p130cas to CrkII, whereas paxillin tyrosine phosphorylation was reduced. These findings support the concepts that CrkII binding activity is regulated by tyrosine kinases and phosphatases, and that tyrosine phosphorylation of CrkII can downmodulate cell migration mediated by the focal adhesion kinase/p130cas pathway

Ophthalmic Surgery in Prion Diseases

Eleven (1.8%) of 597 patients underwent ophthalmic surgery within 1 month before the onset of prion disease or after the onset. All ophthalmologists reused surgical instruments that had been incompletely sterilized to eliminate infectious prion protein. Ophthalmologists should be aware of prion diseases as a possible cause of visual symptoms and use disposable instruments whenever possible

AIR-COOLED MAGNETIC ALLOY CAVITY FOR J-PARC DOUBLED REP.-RATE SCENARIO

Abstract The upgrade project of the J-PARC MR (Main Ring) based on doubled repetition-rate scenario is in progress to deliver the beam power of 750 kW. The present RF section will be occupied by 9 sets of new magnetic alloy, FT3L, cavities using the direct water cooling scheme. The direct water cooling is the efficient scheme to cool the magnetic alloy core although it requires dedicated high-quality cooling water which does not contain copper oxide and copper ions because copper ions may cause the severe corrosion damage on the magnetic alloy cores. These cavities will be used for the fundamental RF for acceleration which requires high duty operation. The second harmonic RF is necessary to increase the bunch length. This allows to enlarge the beam current because it relaxes the space charge effects during the injection. Thanks to the high impedance FT3L and low duty operation of the second harmonic RF, the power loss in the second harmonic RF system becomes moderate. The air cooled cavity is designed to fit in any locations in the MR where the dedicated high-quality water is not available. This paper reports the design of the second RF system, technical issues to produce the magnetic alloy cores to fit the air cooling, and construction of the system

PERFORMANCE OF MULTI-HARMONIC RF FEEDFORWARD SYSTEM FOR BEAM LOADING COMPENSATION IN THE J-PARC RCS

Abstract The beam loading compensation is a key part for acceleration of high intensity proton beams in the J-PARC RCS. In the wide-band MA-loaded RF cavity, the wake voltage consists of not only the accelerating harmonic component but also the higher harmonics. The higher harmonic components cause the RF bucket distortion. We employ the RF feedforward method to compensate the multi-harmonic beam loading. The full-digital feedforward system is developed, which compensates the first three harmonic components of the beam loading. We present the results of the beam test with a high intensity proton beam (2.5 × 10 13 ppp). The impedance seen by the beam is greatly reduced, the impedance of the fundamental accelerating harmonic is reduced to less than 25 Ω in a full accelerating cycle, while the shunt resistance of the cavity is in the order of 800 Ω. The performance of the feedforward system is promising for achievement of the design beam power, 1 MW, in the future

Characterization of Squamate Olfactory Receptor Genes and Their Transcripts by the High-Throughput Sequencing Approach

The olfactory receptor (OR) genes represent the largest multigene family in the genome of terrestrial vertebrates. Here, the high-throughput next-generation sequencing (NGS) approach was applied to characterization of OR gene repertoires in the green anole lizard Anolis carolinensis and the Japanese four-lined ratsnake Elaphe quadrivirgata. Tagged polymerase chain reaction (PCR) products amplified from either genomic DNA or cDNA of the two species were used for parallel pyrosequencing, assembling, and screening for errors in PCR and pyrosequencing. Starting from the lizard genomic DNA, we accurately identified 56 of 136 OR genes that were identified from its draft genome sequence. These recovered genes were broadly distributed in the phylogenetic tree of vertebrate OR genes without severe biases toward particular OR families. Ninety-six OR genes were identified from the ratsnake genomic DNA, implying that the snake has more OR gene loci than the anole lizard in response to an increased need for the acuity of olfaction. This view is supported by the estimated number of OR genes in the Burmese python's draft genome (∼280), although squamates may generally have fewer OR genes than terrestrial mammals and amphibians. The OR gene repertoire of the python seems unique in that many class I OR genes are retained. The NGS approach also allowed us to identify candidates of highly expressed and silent OR gene copies in the lizard's olfactory epithelium. The approach will facilitate efficient and parallel characterization of considerable unbiased proportions of multigene family members and their transcripts from nonmodel organisms