Inhibition of cell movement and proliferation by cell–cell contact-induced interaction of Necl-5 with nectin-3

Immunoglobulin-like Necl-5/Tage4/poliovirus receptor (PVR)/CD155, originally identified as the PVR, has been shown to be up-regulated in cancer cells and to enhance growth factor–induced cell movement and proliferation. In addition, Necl-5 heterophilically trans-interacts with nectin-3, a cell–cell adhesion molecule known to form adherens junctions in cooperation with cadherin. We show here that Necl-5 was down-regulated from cell surface upon cell–cell contacts in NIH3T3 cells. This down-regulation of Necl-5 was initiated by its interaction with nectin-3 and was mainly mediated by clathrin-dependent endocytosis. Then, the down-regulation of Necl-5 induced in this way reduced movement and proliferation of NIH3T3 cells. These results indicate that the down-regulation of Necl-5 induced by its interaction with nectin-3 upon cell–cell contacts may be at least one mechanism underlying contact inhibition of cell movement and proliferation

Update on the Keio collection of Escherichia coli single-gene deletion mutants

The Keio collection (Baba et al, 2006) has been established as a set of single‐gene deletion mutants of Escherichia coli K‐12. These mutants have a precisely designed deletion from the second codon from the seventh to the last codon of each predicted ORF. Further information is available at http://sal.cs.purdue.edu:8097/GB7/index.jsp or http://ecoli.naist.jp/. The distribution is now being handled by the National Institute of Genetics of Japan (http://www.shigen.nig.ac.jp/ecoli/pec/index.jsp). To date more than 4 million samples have been distributed worldwide. As we described earlier (Baba et al, 2006), gene amplification during construction is likely to have led to a small number of mutants with genetic duplications

Refractive Status in Eyes Implanted with Toric and Nontoric Intraocular Lenses during Combined Cataract Surgery and Microhook Ab Interno Trabeculotomy

Purpose. To compare the refractive status between eyes implanted with toric and nontoric intraocular lenses (IOLs) during combined cataract surgery and microhook ab interno trabeculotomy (μLOT), a minimally invasive glaucoma surgery (MIGS). Methods. Twenty eyes of 20 patients who had open-angle glaucoma, cataract, and preexisting regular corneal astigmatism exceeding 1.5 diopters (D) and underwent combined μLOT and phacoemulsification were recruited retrospectively. Ten eyes were implanted with a toric IOL and 10 eyes with a nontoric IOL. The primary outcomes were the uncorrected visual acuity (UCVA) and refractive cylinder at 3 months postoperatively. Results. The mean UCVA of the toric IOL group (logarithm of the minimum angle of resolution (logMAR), 0.23 ± 0.25) was significantly better than that of the nontoric IOL group (logMAR, 0.45 ± 0.26) at 3 months postoperatively (p<0.05). The mean absolute residual refractive cylinder of the nontoric IOL group (2.25 ± 0.62 D) was significantly greater than that of the toric IOL group (1.30 ± 0.68 D) (p<0.05). Postoperatively, 60% of eyes in the toric IOL group and 10% in the nontoric IOL group had an absolute refractive astigmatism level of 1.5 D or less. Surgically induced astigmatism (0.77 ± 0.43 D for toric group and 0.60 ± 0.32 D for nontoric group) and IOP reduction (33.9 ± 15.6% for toric group and 29.4 ± 11.7% for nontoric group) were not different between groups. Conclusions. Use of toric IOL during combined cataract surgery and μLOT is possible and better than not, but physician should prevent their patient of persisting residual astigmatism. The study was registered at https://www.umin.ac.jp/, and the clinical trial accession number is https://clinicaltrials.gov/ct2/show/UMIN000043141

Variation of Urate Transport in the Nephrons in Subtypes of Hyperuricemia

Background: Hyperuricemia cases (HU) can be classified into four subgroups by combining the two main causes of hyperuricemia, i.e. urate underexcretion and overproduction. These subgroups are as follows: underexcretion-type cases (UE); overproduction-type cases (OP); combined-type cases, and normal-type cases. Since urinary urate excretion (Uua) and urate clearance differ significantly between UE and OP, urate transport in the nephrons and the intratubular urate contents might also differ. Such differences might help clarify the pathophysiology of urate underexcretion in subgroups of hyperuricemia, and thus reveal its underlying mechanisms. Methods: Urate transport coefficients in each subtype of HU were determined employing the previously reported benzbromarone-loading urate clearance tests. The subtype cases of HU were plotted on a graph of urate transport coefficients versus Uua as coordinates. The characteristic features in the distribution of subtype cases on graphs were analyzed in relation to Uua. Results: The mean (±standard error) tubular secretion rate (TSR) in the UE (48.7 ± 1.7 ml/min) was significantly lower and the postsecretory urate reabsorption rate (R2) in the UE (0.904 ± 0.004) was significantly higher than those in the normal controls (78.0 ± 2.1 ml/min and 0.877 ± 0.003) or the OP (61.1 ± 3.2 ml/min and 0.861 ± 0.009). Decrements of TSR and increments of R2 in the UE were largest in the subtypes of the HU, in terms of case numbers and the deviation rate of the group. Conversely, decrements of TSR and increments of R2 were smallest in the OP. A significant correlation was identified between TSR and Uua (r = 0.345, p 2 and Uua (r = -0.393, p Conclusion: In the UE, hyperuricemia is induced mainly by urate underexcretion, which results from the combination of two main causes in urate transporters of the nephron: significantly lower TSR and significantly higher R2. Neither of these was observed in OP. Differences in urate transporters in subtypes of the HU might be important not only for understanding the pathophysiology and mechanisms of urate underexcretion and hyperuricemia, but also for providing a strategic therapy for hyperuricemia