The ganglioside GM3 synthase (SAT-I), encoded by a single-copy gene, is a primary glycosyltransferase for the synthesis of complex gangliosides. In SAT-I null mice, hearing ability, assessed by brainstem auditory-evoked potentials (BAEP), was impaired at the onset of hearing and had been completely lost by 17 days after birth (P17), showing a deformity in hair cells in the organ of Corti. By 2 months of age, the organ of Corti had selectively and completely disappeared without effect on balance or motor function or in the histology of vestibule. Interestingly, spatiotemporal changes in localization of individual gangliosides, including GM3 and GT1b, were observed during the postnatal development and maturation of the normal inner ear. GM3 expressed in almost all regions of cochlea at P3, but at the onset of hearing it distinctly localized in stria vascularis, spiral ganglion, and the organ of Corti. In addition, SAT-I null mice maintain the function of stria vascularis, because normal potassium concentration and endocochlear potential of endolymph were observed even when they lost the BAEP completely. Thus, the defect of hearing ability of SAT-I null mice could be attributed to the functional disorganization of the organ of Corti, and the expression of gangliosides, especially GM3, during the early part of the functional maturation of the cochlea could be essential for the acquisition and maintenance of hearing function.auditory system ͉ cochlea ͉ deafness ͉ knockout mice ͉ sialyltransferase G angliosides [i.e., glycosphingolipids (GSLs)] containing sialic acid are abundant in central nervous tissues and are considered to have important roles in controlling development, proliferation, differentiation, and maintenance of neural tissues and cells (1). Gangliosides usually reside in the outer leaflet of the cell membrane and are concentrated in microdomains specialized for cell adhesion and cell signaling (2, 3). The first product in the biosynthetic pathway of the ganglio-series gangliosides is GM3, which serves as a common precursor for the a-series and b-series gangliosides (Fig. 1). The sialyltransferase responsible for GM3 synthesis is the GM3 synthase (EC 2.4.99.9), also known by the names SAT-I (used here), ST3GalV, and Siat 9. The gene encoding this enzyme has been identified by several research laboratories, including ours (4-6).In the study presented here, we generated mice deficient in GM3 synthase (SAT-I Ϫ/Ϫ mice) (7) and examined their general behavior, including their motor function, learning and memory, and sensory function. Interestingly, SAT-I Ϫ/Ϫ mice exhibited no startle reflex in response to various acoustic stimulations, yet they did demonstrate normal startle responses to air puffing, suggesting a hearing impairment. Electrophysiological and histological analyses of the auditory system of the SAT-I Ϫ/Ϫ mice further revealed that the organ of Corti in the inner ear is selectively degenerated in these animals. ResultsAbsence of Acoustic Startle Response in SAT-I Null Mice. GM3 synthase null (SAT...

Previous short-term experiments showed that trail following behavior of the Argentine ant, Linepithema humile (Mayr) (Hymenoptera: Formicidae), can be disrupted by a high concentration of synthetic trail pheromone component (Z)-9-hexadecenal. In this study, a long-term field trial was conducted in 100-m2 plots of house gardens in an urban area of Japan to see whether the control effect on Argentine ants can be obtained by permeating synthetic trail pheromone from dispensers. The dispensers were placed in the experimental plots during the ant's active season (April-November) for 2 yr with monthly renewal. To estimate Argentine ant population density, foraging activity of Argentine ants in the study plots was monitored by monthly bait surveys. Throughout the study period, Argentine ant foraging activity was suppressed in the presence of the dispensers, presumably via trail forming inhibition. In contrast, the level of foraging activity was not different between treatment and no-treatment plots when the dispensers were temporarily removed, suggesting that treatment with pheromone dispensers did not suppress Argentine ant density in the treatment plots. Population decline may be expected with larger-scale treatment that covers a significant portion of the ant colony or with improvement in the potency of the disruptant.

Many invasive ants, including the Argentine ant Linepithema humile, form expansive supercolonies, within which intraspecific aggression is absent. The behavioral relationships among introduced Argentine ant populations at within-country or within-continent scales have been studied previously, but the behavioral relationships

Neutron diffraction measurements have been carried out on aqueous 10, 25, and 33 mol% LiBr solutions. The 6Li/7Li isotopic substitution technique was applied to determine the local structure around Li+ in these solutions. The least-squares fitting analysis was successfully adopted both for the observed Li+ difference interference function, ΔLi(Q), and for the Li+ distribution function GLi(r). The nearest neighbor Li+···O distance in the solutions was obtained to be 1.96 ± 0.02 Å, which agrees well with that reported in previous neutron diffraction studies. The average hydration number of Li+ decreases from ca. 6 for the 10 mol% LiBr solution to ca. 4 for the 25 mol% LiBr solution. The tetrahedral hydration structure around Li+ appeared to stay even in the 33 mol% LiBr solution. The Li+···Br− correlation was found at 3.4 Å in the 33 mol% LiBr solution. This value rather suggests the formation of the solvent-shared ion pair, Li+···D2O···Br−.

Combination treatment may be a more effective and environmentally friendly method for controlling invasive ants than conventional methods. Extermination of ants by insecticidal bait and inhibition of re-infestation by pheromone may be the mechanism of the combination effect. This is the first study to show a significant effect of synthetic trail pheromone on ant population.

Background: Pulmonary endarterectomy (PEA) is the standard treatment for chronic thromboembolic pulmonary hypertension (CTEPH), although some patients may experience residual pulmonary hypertension (PH). It is unclear whether balloon pulmonary angioplasty (BPA) is effective for residual PH after PEA. This study aimed to compare the BPA outcomes between patients with residual PH after PEA and those with inoperable CTEPH. Methods: This retrospective study compared BPA for residual PH after PEA (25 patients, 101 BPA sessions) and BPA alone for inoperable CTEPH (21 patients, 89 BPA sessions). All patients underwent right heart catheterisation and functional and laboratory tests before PEA or before and after BPA. Results: There was no difference in the number of BPA sessions per patient (4.0 ± 1.9 vs. 4.2 ± 1.9, p = 0.671). No significant differences were observed with respect to the mean pulmonary artery pressure (23.6 ± 9.1 vs. 21.9 ± 5.7 mmHg, p = 0.44), pulmonary vascular resistance (3.7 ± 0.5 vs. 2.8 ± 1.2 Wood units, p = 0.14), 6-min walking distance (392.1 ± 117.7 vs. 452.4 ± 90.1 m, p = 0.096), and World Health Organization functional class (I/II/ III/IV: 14/11/0/0 vs. 9/12/0/0, p = 0.375). Severe haemoptysis requiring embolisation was more common in the PH after PEA group (16.0% vs. 5.4%, p = 0.018). However, no patients required mechanical ventilation or extracorporeal membrane oxygenation, and there were no procedural deaths. Conclusion: Although BPA might be effective for residual PH after PEA, it was associated with a high rate of haemoptysis.

Development of designer natural product variants, 6-aza-artemisinins, enabled us to achieve structural modification of the hitherto unexplored cyclohexane moiety of artemisinin and concise de novo synthesis of the tetracyclic scaffold in just four steps from the modular assembly of three simple building blocks. This expeditious catalytic asymmetric synthetic approach generated lead candidates exhibiting superior in vivo antimalarial activities to artemisinin.

No abstract