Loss of IκBζ Drives Dentin Formation via Altered H3K4me3 Status.

Enforced enrichment of the active promoter marks trimethylation of histone H3 lysine 4 (H3K4me3) and acetylation of histone H3 lysine 27 (H3K27ac) by inhibiting histone demethylases and deacetylases is positively associated with hard tissue formation through the induction of osteo/odontogenic differentiation. However, the key endogenous epigenetic modulator of odontoblasts to regulate the expression of genes coding dentin extracellular matrix (ECM) proteins has not been identified. We focused on nuclear factor (NF)-κB inhibitor ζ (IκBζ), which was originally identified as the transcriptional regulator of NF-κB and recently regarded as the NF-κB-independent epigenetic modulator, and found that IκBζ null mice exhibit a thicker dentin width and narrower pulp chamber, with aged mice having more marked phenotypes. At 6 mo of age, dentin fluorescent labeling revealed significantly accelerated dentin synthesis in the incisors of IκBζ null mice. In the molars of IκBζ null mice, marked tertiary dentin formation adjacent to the pulp horn was observed. Mechanistically, the expression of COL1A2 and COL1A1 collagen genes increased more in the odontoblast-rich fraction of IκBζ null mice than in wild type in vivo, similar to human odontoblast-like cells transfected with small interfering RNA for IκBζ compared with cells transfected with control siRNA in vitro. Furthermore, the direct binding of IκBζ to the COL1A2 promoter suppressed COL1A2 expression and the local active chromatin status marked by H3K4me3. Based on whole-genome identification of H3K4me3 enrichment, ECM and ECM organization-related gene loci were selectively activated by the knockdown of IκBζ, which consistently resulted in the upregulation of these genes. Collectively, this study suggested that IκBζ is the key negative regulator of dentin formation in odontoblasts by inhibiting dentin ECM- and ECM organization-related gene expression through an altered local chromatin status marked by H3K4me3. Therefore, IκBζ is a potential target for epigenetically improving the clinical outcomes of dentin regeneration therapies such as pulp capping.

Three patients with advanced cutaneous angiosarcoma treated with eribulin: investigation of serum soluble CD163 and chemokine (C-X-C motif) ligand 10 as possible biomarkers predicting the biological behaviour of angiosarcoma.

Cutaneous angiosarcoma (CAS) is a highly aggressive vascular tumour that recurs locally and metastasizes early. Although chemoradiotherapy with taxanes shows a high response rate with prolonged survival, second-line therapy for advanced CAS remains contentious. This report describes three patients with advanced CAS treated with eribulin. In addition, we investigated serum soluble (s)CD163, chemokine (C-X-C motif) ligand 10 (CXCL10) and chemokine (C-C motif) ligand 2 levels at several time points of tumour progression in these patients, revealing serum levels of sCD163 and CXCL10 as potential biomarkers for progression of CAS.

Evaluation of wheat gluten in milk replacers and calf starters.

Two trials were conducted to evaluate wheat gluten as an ingredient in calf feeds. In one trial, Holstein bull calves (n = 120) were assigned for 6 wk to one of five milk replacers, which contained different percentages of CP and different percentages of protein furnished from soluble wheat gluten. Within a given protein percentage, BW gains of calves were not affected by the percentage of protein that was supplied as wheat gluten. Calves fed milk replacer containing 18% CP with 33% wheat gluten gained as much as calves fed replacers containing 20% CP. In another trial, newborn Holstein calves (n = 62) were used. Protein supplements of the calf starters used until 7 wk of age were either soybean meal or spray-dried wheat gluten and soybean meal. No significant differences were observed between the two treatments. Also, no significant carry-over effect occurred when all calves received a common diet from 7 to 10 wk of age.

Circadian variation of urinary enzymes in the dog.

Circadian variations of N-acetyl-beta-D-glucosamidase (NAG, EC 3.2.1.30) and gamma-glutamyl transpeptidase (gamma-GTP, EC 2.3.2.2) were examined in dogs. Urine and blood were collected at 4-hr intervals from adult mongrel dogs (11 males, 11 females) weighing between 7 and 13 kg. The collected urine and blood were used to measure creatinine, NAG and gamma-GTP. The amount of urine was significantly higher (p < 0.05) during the period from 12:00 to 16:00. Creatinine clearance did not show any characteristic variations and creatinine excretion was significantly higher (p < 0.05) during the period from 8:00 to 16:00. No characteristic variations were observed in the amounts excreted, activity, or NAG and gamma-GTP creatinine index. There were high correlations between creatinine excretion and creatinine clearance (r = 0.693), gamma-GTP excretion and gamma-GTP creatinine index (r = 0.724), NAG excretion and NAG creatinine index (r = 0.878), and between the NAG and gamma-GTP creatinine index of each 4-hr specimen and the NAG and gamma-GTP excretion of the 24-hr specimens. These results suggest the diagnostic usefulness measuring enzyme activity in non-periodically collected urine.

Evaluation of urinary enzymes in dogs with early renal disorder.

We investigated urinary N-acetyl-beta-D-glucosaminidase NAG (EC 3.2.1.30), gamma-glutamyl transpeptidase gamma-GTP (EC 2.3.2.2) and glycyl-prolyl dipeptidyl aminopeptidase GP-DAP (EC 3.4.14.5) in dogs with heartworm disease and renal failure. In the renal failure dogs, the NAG, gamma-GTP and GP-DAP index were significantly higher than those in the healthy dogs. In the heartworm disease dogs with normal chest X-rays (HW I), none of the enzyme values was significantly different from those of the healthy controls. In the dogs with heartworm disease showing abnormal heart shadows on their chest X-rays (HW II), enzyme values were significantly higher than those in the healthy dogs (P < 0.01) and the HW I dogs (P < 0.01). Thus, these urinary enzymes tests are available for the early detection of renal disorders.

Optical waveguide 2 x 2 matrix switch using dielectric chip motion.

Input and output light angles in a total internal reflection optical waveguide switch, in which a guided light beam is switched by dielectric chip contact with a low-index channel built in a waveguide film, are studied to construct a matrix switch. Output angle depends on channel width, chip contact width, chip position, and input angle. In a single switch experiment, the output angle is larger than the total reflection critical angle for the channel due to narrow chip contact width. By utilizing this property, a nonblocking 2 x 2 matrix switch, driven by PZT bimorphs, is fabricated. Insertion losses of 2.9-6.0 dB, cross talk values of 10.8-28.1 dB, and switching time of 6 msec are obtained for the TE(0) mode at 0.633-microm wavelength.

Total reflection optical waveguide switching through dielectric chip motion.

An optical waveguide switch has been realized utilizing the total reflection critical angle controlled by the motion of a dielectric chip set on a waveguide surface. By the contact-noncontact of a GGG chip with the SiO(2)-Ta(2)O(5) waveguide film having a built-in low refractive-index channel, a switching angle of 22.5x and extincion ratio of 12-16 dB were obtained for the TE(0) mode at 0.633-microm wavelength. A 1 x 3 switch that includes two switching positions driven by 6-V electromagnets is demonstrated.

Optical-mode filters using coupling between two nonidentical waveguides.

Novel optical-waveguide mode filters, based on mode-selective coupling between nonidentical waveguides and attenuation in a lossy waveguide, are proposed and demonstrated. Both TE(0) and TM(0) mode filters were fabricated from glass compositions by rf-sputtering. For both the TE(0) and TM(0) mode filters, insertion losses were 2.1 dB and 1.1 dB, respectively, and attentuations for undesirable modes were 16.8 dB and 21.6 dB, respectively.

Optical demultiplexer using coupling between nonidentical waveguides.

A demultiplexer using wavelength dependent coupling between nonidentical waveguides is proposed and demonstrated for single-mode fiber transmission systems. The demultiplexer, consisting of rf-sputtered glass thin film layers, demultiplexes 4880-A, 5145-A, and 6328-A light waves with larger than 14-dB crosstalk attenuations and with less than 5.2-dB insertion losses.