Pituitary adenylate cyclase-activating polypeptide type 1 receptor signaling evokes long-lasting nociceptive behaviors through the activation of spinal astrocytes in mice

AbstractIntrathecal (i.t.) administration of pituitary adenylate cyclase-activating polypeptide (PACAP) induces long-lasting nociceptive behaviors for more than 60 min in mice, while the involvement of PACAP type1 receptor (PAC1-R) has not been clarified yet. The present study investigated signaling mechanisms of the PACAP-induced prolonged nociceptive behaviors. Single i.t. injection of a selective PAC1-R agonist, maxadilan (Max), mimicked nociceptive behaviors in a dose-dependent manner similar to PACAP. Pre- or post-treatment of a selective PAC1-R antagonist, max.d.4, significantly inhibited the nociceptive behaviors by PACAP or Max. Coadministration of a protein kinase A inhibitor, Rp-8-Br-cAMPS, a mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase inhibitor, PD98059 or a c-Jun N-terminal kinase (JNK) inhibitor, SP600125, significantly inhibited the nociceptive behaviors by Max. Immunohistochemistry and immunoblotting analysis revealed that spinal administration of Max-induced ERK phosphorylation and JNK phosphorylation, and also augmented an astrocyte marker, glial fibrillary acidic protein in mouse spinal cord. Furthermore, an astroglial toxin, l-α-aminoadipate, significantly attenuated the development of the nociceptive behaviors and ERK phosphorylation by Max. These results suggest that the activation of spinal PAC1-R induces long-lasting nociception through the interaction of neurons and astrocytes

Power-law behavior in the power spectrum induced by Brownian motion of a domain wall

We show that Brownian motion of a one-dimensional domain wall in a large but finite system yields a $\omega^{-3/2}$ power spectrum. This is successfully applied to the totally asymmetric simple exclusion process (TASEP) with open boundaries. An excellent agreement between our theory and numerical results is obtained in a frequency range where the domain wall motion dominates and discreteness of the system is not effective.Comment: 4 pages, 4 figure

Giant Anomalous Hall Conductivity at the Pt/Cr₂O₃ Interface

The interface between a magnetic material and a heavy metal that has a large spin-orbit interaction is at the root of various spin-related phenomena. In this paper, we address the peculiar spin-dependent transport at a Pt/Cr₂O₃ interface by exploring the origin of the nonlinear anomalous Hall effect (AHE) in Pt/Cr₂O₃ bilayers. X-ray magnetic circular dichroism (XMCD) measurements show no appreciable magnetic moment at the interface originating from Cr 3d and Pt 5d orbitals, which could be associated with the AHE response. A possible interfacial magnetic moment M at the Pt/Cr₂O₃ interface, assumed from the detection limit of the XMCD measurements, yields an anomalous Hall conductivity (σAHE) per unit net magnetic moment (M),-σAHE/M, of 0.57 V-1, which is extraordinary large compared with that for general magnetic materials. Together with first-principles calculations, the results suggest the possibility of an intrinsic AHE in the Pt/Cr₂O₃ interface that does not rely on the net magnetic moment.T.Moriyama, Y.Shiratsuchi, T.Iino, et al. Giant Anomalous Hall Conductivity at the Pt/Cr₂O₃ Interface. Physical Review Applied 13, 034052 (2020); https://doi.org/10.1103/PhysRevApplied.13.034052

Template properties of mutagenic cytosine analogues in reverse transcription

We have studied the mutagenic properties of ribonucleotide analogues by reverse transcription to understand their potential as antiretroviral agents by mutagenesis of the viral genome. The templating properties of nucleotide analogues including 6-(β-D-ribofuranosyl)-3,4-dihydro-8H-pyrimido[4,5-c](1,2)oxazin-7-one, N(4)-hydroxycytidine, N(4)-methoxycytidine, N(4)-methylcytidine and 4-semicarbazidocytidine, which have been reported to exhibit ambiguous base pairing properties, were examined. We have synthesized RNA templates using T3 RNA polymerase, and investigated the specificity of the incorporation of deoxyribonucleoside triphosphates opposite these cytidine analogues in RNA by HIV and AMV reverse transcriptases. Except for N(4)-methylcytidine, both enzymes incorporated both dAMP and dGMP opposite these analogues in RNA. This indicates that they would be highly mutagenic if present in viral RNA. To study the basis of the differences among the analogues in the incorporation ratios of dAMP to dGMP, we have carried out kinetic analysis of incorporation opposite the analogues at a defined position in RNA templates. In addition, we examined whether the triphosphates of these analogues were incorporated competitively into RNA by human RNA polymerase II. Our present data supports the view that these cytidine analogues are mutagenic when incorporated into RNA, and that they may therefore be considered as candidates for antiviral agents by causing mutations to the retroviral genome

Factors in glucocorticoid regimens associated with treatment response and relapses of IgG4-related disease: a multicentre study

Glucocorticoids (GC) are effective for treating IgG4-related disease (IgG4-RD); however, relapse is often observed. We conducted a retrospective multicentre study to investigate risk factors in GC regimens associated with relapses of IgG4-RD. Data on 166 patients with definitive IgG4-RD diagnosis were collected from 12 institutions. Comprehensive surveillance of clinical backgrounds and GC regimens as well as multivariate analysis of factors associated with treatment responses and relapses was performed. To determine the initial maximal GC dose, the patients were stratified into three groups depending on the initial prednisolone (PSL) dosage: 0.7 mg/kg/day. The multivariate analysis extracted the disease duration and reduction speed of initial GC dose. Patients treated with initial GC 0.7 mg/kg/day of PSL showed higher relapse rates than those treated with 0.4–0.69 mg/kg/day. The relapse rates were significantly higher in patients with fast reduction of the initial dose (>0.4 mg/day) than in patients with slow reduction (<0.4 mg/day). To avoid relapse, 0.4–0.69 mg/kg/day of initial PSL with slow reduction speed (<0.4 mg/day) is needed in the early treatment of IgG4-RD

Effects of the development changes in dentition on the retention of mouthguards

Summary The use of mouthguards is one of the main strategies that are considered effective in preventing sports–related trauma.Although mouthguards are recommended for use in children during sports activities,little is known as to how growth and developmental changes in the oral cavity, jaw, and dentition affect the retention of mouthguards. In the present study, we designed mouthguards for primary,mixed(4 types),and permanent detention stages and performed tensile testing to determine the effects of dental growth and development on their retention.We also designed mouthguards for the left maxillary second milk molar,left maxillary second premolar, and left maxillary first molar to determine how the shape of the teeth affects their retention.Data was analyzed statistically,and the following results were obtained:1.Mouthguards for permanent detention stage had a significantly higher level of retention than those for primary and mixed detention stages.2.Mouthguards for primary detention stage had a significantly lower level of retention than those for mixed and permanent detention stages. 3.The retention of mixed detention stage mouthguards became poorer with the number of teeth requiring relief.4.Differences in the shape of the teeth(left maxillary second milk molar, left maxillary second premolar, left maxillary first molar)had no significant effect on the retention of mouthguards.These findings indicate that the level of mouthguard retention is lower in children at primary and mixed detention stages than in adults and children with complete eruption of central incisor to second molar.This difference may be attributed to the differences in the coverage areas of mouthguard