O-linked ß-N-acetylglucosamine modification of proteins is essential for foot process maturation and survival in podocytes.

BACKGROUND: O-linked ß- N -acetylglucosamine modification O-GlcNAcylation) is a post-translational modification of intracellular proteins, serving as a nutrient sensor. Growing evidence has demonstrated its physiological and pathological importance in various mammalian tissues. This study examined the physiological role of O-GlcNAcylation in podocyte function and development. METHODS: O-GlcNAc transferase (Ogt) is a critical enzyme for O-GlcNAcylation and resides on the X chromosome. To abrogate O-GlcNAcylation in podocytes, we generated congenital and tamoxifen (TM)-inducible podocyte-specific Ogt knockout mice (Podo-Ogt y/- and TM-Podo-Ogt y/- , respectively) and analyzed their renal phenotypes. RESULTS: Podo-Ogt y/- mice showed normal podocyte morphology at birth. However, they developed albuminuria at 8 weeks of age, increasing progressively until age 32 weeks. Glomerular sclerosis, proteinuria-related tubulointerstitial lesions and markedly altered podocyte foot processes, with decreased podocin expression, were observed histologically in 32-week-old Podo-Ogt y/- mice. Next, we induced adult-onset deletion of the Ogt gene in podocytes by TM injection in 8-week-old TM-Podo-Ogt y/- mice. In contrast to Podo-Ogt y/- mice, the induced TM-Podo-Ogt y/- mice did not develop albuminuria or podocyte damage, suggesting a need for O-GlcNAcylation to form mature foot processes after birth. To test this possibility, 3-week-old Podo-Ogt y/- mice were treated with Bis-T-23, which stimulates actin-dependent dynamin oligomerization, actin polymerization and subsequent foot process elongation in podocytes. Albuminuria and podocyte damage in 16-week-old Podo-Ogt y/- mice were prevented by Bis-T-23 treatment. CONCLUSIONS: O-GlcNAcylation is necessary for maturation of podocyte foot processes, particularly after birth. Our study provided new insights into podocyte biology and O-GlcNAcylation.

Performance evaluation of the sulfur-redox-reaction-activated up-flow anaerobic sludge blanket and down-flow hanging sponge anaerobic/anoxic sequencing batch reactor system for municipal sewage treatment.

A sulfur-redox-reaction-activated up-flow anaerobic sludge blanket (UASB) and down-flow hanging sponge (DHS) system, combined with an anaerobic/anoxic sequencing batch reactor (A2SBR), has been used for municipal sewage treatment for over 2 years. The present system achieved a removal rate of 95±14% for BOD, 74±22% for total nitrogen, and 78±25% for total phosphorus, including low water temperature conditions. Sludge conversion rates during the operational period were 0.016 and 0.218 g-VSS g-COD-removed(-1) for the UASB, and DHS, respectively, which are similar to a conventional UASB-DHS system, which is not used of sulfur-redox-reaction, for sewage treatment. Using the sulfur-redox reaction made advanced treatment of municipal wastewater with minimal sludge generation possible, even in winter. Furthermore, the occurrence of a unique phenomenon, known as the anaerobic sulfur oxidation reaction, was confirmed in the UASB reactor under the winter season.

Focal Segmental Glomerular Sclerosis Ameliorated by Long-term Hemodialysis Therapy with Low-density Lipoprotein Apheresis.

We report a case involving a 43-year-old Japanese woman with steroid-resistant focal segmental glomerular sclerosis (FSGS) and severe renal dysfunction, which was ameliorated by low-density lipoprotein apheresis (LDL-A). She had been treated with steroid therapy, but had experienced anuria for over 10 weeks and required hemodialysis. She was then treated with LDL-A, which resulted in improved urinary protein excretion and renal function. Her renal function recovered after 97 days of hemodialysis therapy. This case suggests that LDL-A may represent an effective rescue treatment in patients with FSGS and long-term anuria.

Molecular characterization of anaerobic sulfur-oxidizing microbial communities in up-flow anaerobic sludge blanket reactor treating municipal sewage.

A novel wastewater treatment system consisting of an up-flow anaerobic sludge blanket (UASB) reactor and a down-flow hanging sponge (DHS) reactor with sulfur-redox reaction was developed for treatment of municipal sewage under low-temperature conditions. In the UASB reactor, a novel phenomenon of anaerobic sulfur oxidation occurred in the absence of oxygen, nitrite and nitrate as electron acceptors. The microorganisms involved in anaerobic sulfur oxidation have not been elucidated. Therefore, in this study, we studied the microbial communities existing in the UASB reactor that probably enhanced anaerobic sulfur oxidation. Sludge samples collected from the UASB reactor before and after sulfur oxidation were used for cloning and terminal restriction fragment length polymorphism (T-RFLP) analysis of the 16S rRNA genes of the bacterial and archaeal domains. The microbial community structures of bacteria and archaea indicated that the genus Smithella and uncultured bacteria within the phylum Caldiserica were the dominant bacteria groups. Methanosaeta spp. was the dominant group of the domain archaea. The T-RFLP analysis, which was consistent with the cloning results, also yielded characteristic fingerprints for bacterial communities, whereas the archaeal community structure yielded stable microbial community. From these results, it can be presumed that these major bacteria groups, genus Smithella and uncultured bacteria within the phylum Caldiserica, probably play an important role in sulfur oxidation in UASB reactors.

Facial vibrotactile stimulation activates the parasympathetic nervous system: study of salivary secretion, heart rate, pupillary reflex, and functional near-infrared spectroscopy activity.

We previously found that the greatest salivation response in healthy human subjects is produced by facial vibrotactile stimulation of 89 Hz frequency with 1.9 µ m amplitude (89 Hz-S), as reported by Hiraba et al. (2012, 20011, and 2008). We assessed relationships between the blood flow to brain via functional near-infrared spectroscopy (fNIRS) in the frontal cortex and autonomic parameters. We used the heart rate (HRV: heart rate variability analysis in RR intervals), pupil reflex, and salivation as parameters, but the interrelation between each parameter and fNIRS measures remains unknown. We were to investigate the relationship in response to established paradigms using simultaneously each parameter-fNIRS recording in healthy human subjects. Analysis of fNIRS was examined by a comparison of various values between before and after various stimuli (89 Hz-S, 114 Hz-S, listen to classic music, and "Ahh" vocalization). We confirmed that vibrotactile stimulation (89 Hz) of the parotid glands led to the greatest salivation, greatest increase in heart rate variability, and the most constricted pupils. Furthermore, there were almost no detectable differences between fNIRS during 89 Hz-S and fNIRS during listening to classical music of fans. Thus, vibrotactile stimulation of 89 Hz seems to evoke parasympathetic activity.

Imaging of a large collection of human embryo using a super-parallel MR microscope.

Using 4 and 8-channel super-parallel magnetic resonance (MR) microscopes with a horizontal bore 2.34T superconducting magnet developed for 3-dimensional MR microscopy of the large Kyoto Collection of Human Embryos, we acquired T(1)-weighted 3D images of 1204 embryos at a spatial resolution of (40 microm)(3) to (150 microm)(3) in about 2 years. Similarity of image contrast between the T(1)-weighted images and stained anatomical sections indicated that T(1)-weighted 3D images could be used for an anatomical 3D image database for human embryology.