Role of satellite cell-derived l-serine in the dorsal root ganglion in paclitaxel-induced painful peripheral neuropathy

Paclitaxel is one of the most commonly used antineoplastic drugs for the treatment of solid tumors. Unfortunately, its use is often associated with dose-limiting painful peripheral neuropathy and subsequent neuropathic pain that is resistant to standard analgesics. However, there are few clinically available drugs or drug classes for the treatment of paclitaxel-induced neuropathy due to a lack of information regarding the mechanisms responsible for it. In this study, we examined the involvement of L-serine in paclitaxel-induced hyperalgesia/allodynia and decrease in sensory nerve conduction velocity (SNCV). We used a preclinical rat model of paclitaxel-induced painful peripheral neuropathy. Response to von Frey filaments, SNCV, 3-phosphoglycerate dehydrogenase (3PGDH) expression, and L-serine concentration were examined. Effects of L-serine administration were also investigated. Paclitaxel treatment induced mechanical allodynia/hyperalgesia and reduction of SNCV. Paclitaxel also decreased the L-serine concentration in the dorsal root ganglion (DRG) but not in the sciatic nerve or spinal cord. In addition, paclitaxel decreased expression of 3PGDH, a biosynthetic enzyme of L-serine, in the DRG. Immunohistochemistry showed that 3PGDH was localized in satellite cells but not in neurons in the DRG. Intraperitoneal administration of L-serine improved both paclitaxel-induced mechanical allodynia/hyperalgesia and the reduction of SNCV. These results suggest that satellite cell-derived L-serine in the DRG plays an important role in paclitaxel-induced painful peripheral neuropathy. These findings may lead to novel strategies for the treatment of paclitaxel-induced painful peripheral neuropathy.ArticleNEUROSCIENCE. 174(0):190-199 (2011)journal articl

Bulk electronic state of superconducting topological insulator

We study electronic properties of a superconducting topological insulator whose parent material is a topological insulator. We calculate the temperature dependence of the specific heat and spin susceptibility for four promising superconducting pairings proposed by L. Fu and E. Berg (Phys. Rev. Lett. 105, 097001). Since the line shapes of temperature dependence of specific heat are almost identical among three of the four pairings, it is difficult to identify them simply from the specific heat. On the other hand, we obtain wide varieties of the temperature dependence of spin susceptibility for each pairing reflecting the spin structure of Cooper pair. We propose that the pairing symmetry of superconducting topological insulator can be determined from measurement of Knight shift by changing the direction of applied magnetic field.Comment: 12 pages, 15 figures. Accepted for publication in J. Phys. Soc. Jp

Suppression of bone marrow-derived microglia in the amygdala improves anxiety-like behavior induced by chronic partial sciatic nerve ligation in mice

大脳辺縁系の一部である扁桃体は，不快情動の形成において重要な役割を担っている．我々は，神経障害性疼痛の慢性期に扁桃体中心核に集積する骨時由来ミクログリアが IL-1βを分泌して神経細胞に作用することで，慢性疼痛における不快情動の形成に関与することを明らかにした

Significance of Off-Center Rattling for Emerging Low-lying THz Modes in type-I Clathrates

We show that the distinct differences of low-lying THz-frequency dynamics between type-I clathrates with on-center and off-center guest ions naturally follow from a theoretical model taking into account essential features of the dynamics of rattling guest ions. Our model analysis demonstrates the drastic change from the conventional dynamics shown by on-center systems to the peculiar dynamics of off-center systems in a unified manner. We claim that glass-like plateau thermal conductivities observed for off-center systems stem from the flattening of acoustic phonon dispersion in the regime |k|<|G|/4. The mechanism is applicable to other systems such as glasses or relaxers

Flat edge modes of graphene and of Z2 topological insulator

A graphene nano-ribbon in the zigzag edge geometry exhibits a specific type of gapless edge modes with a partly flat band dispersion. We argue that the appearance of such edge modes are naturally understood by regarding graphene as the gapless limit of a Z2 topological insulator. To illustrate this idea, we consider both Kane-Mele (graphene-based) and Bernevig-Hughes-Zhang models: the latter is proposed for HgTe/CdTe 2D quantum well. Much focus is on the role of valley degrees of freedom, especially, on how they are projected onto and determine the 1D edge spectrum in different edge geometries

Spin-orbit effects in a graphene bipolar pn junction

A graphene $pn$ junction is studied theoretically in the presence of both intrinsic and Rashba spin-orbit couplings. We show that a crossover from perfect reflection to perfect transmission is achieved at normal incidence by tuning the perpendicular electric field. By further studying angular dependent transmission, we demonstrate that perfect reflection at normal incidence can be clearly distinguished from trivial band gap effects. We also investigate how spin-orbit effects modify the conductance and the Fano factor associated with a potential step in both $nn$ and $np$ cases.Comment: 6 pages, 5 figures, conductance and Fano factor plots adde

Edge Current due to Majorana Fermions in Superfluid 3^3He A- and B-Phases

We propose a method utilizing edge current to observe Majorana fermions in the surface Andreev bound state for the superfluid $^3$He A- and B-phases. The proposal is based on self-consistent analytic solutions of quasi-classical Green's function with an edge. The local density of states and edge mass current in the A-phase or edge spin current in the B-phase can be obtained from these solutions. The edge current carried by the Majorana fermions is partially cancelled by quasiparticles (QPs) in the continuum state outside the superfluid gap. QPs contributing to the edge current in the continuum state are distributed in energy even away from the superfluid gap. The effect of Majorana fermions emerges in the depletion of the edge current by temperature within a low-temperature range. The observations that the reduction in the mass current is changed by $T^2$-power in the A-phase and the reduction in the spin current is changed by $T^3$-power in the B-phase establish the existence of Majorana fermions. We also point out another possibility for observing Majorana fermions by controlling surface roughness.Comment: 13 pages, 4 figures, published versio

An international validation study of the IL-2 Luc assay for evaluating the potential immunotoxic effects of chemicals on T cells and a proposal for reference data for immunotoxic chemicals

To evaluate the immunotoxic effects of xenobiotics, we have established the Multi-ImmunoTox assay, in which three stable reporter cell lines are used to evaluate the effects of chemicals on the IL-2, IFN-\u3b3, IL-1\u3b2 and IL-8 promoters. Here, we report the official validation study of the IL-2 luciferase assay (IL-2 Luc assay). In the Phase I study that evaluated five coded chemicals in three sets of experiments, the average within-laboratory reproducibility was 86.7%. In the Phase II study, 20 coded chemicals were evaluated at multiple laboratories. In the combined results of the Phase I and II studies, the between-laboratory reproducibility was 80.0%. These results suggested that the IL-2 Luc assay was reproducible both between and within laboratories. To determine the predictivity, we collected immunotoxicological information and constructed the reference data by classifying the chemical into immunotoxic compounds targeting T cells or others according to previously reported criteria. When compared with the reference data, the average predictivity of the Phase I and II studies was 75.0%, while that of additional 60 chemicals examined by the lead laboratory was 82.5%. Although the IL-2 Luc assay alone is not sufficient to predict immunotoxicity, it will be a useful tool when combined with other immune tests

Dual role of cerebral blood flow in regional brain temperature control in the healthy newborn infant.

Small shifts in brain temperature after hypoxia-ischaemia affect cell viability. The main determinants of brain temperature are cerebral metabolism, which contributes to local heat production, and brain perfusion, which removes heat. However, few studies have addressed the effect of cerebral metabolism and perfusion on regional brain temperature in human neonates because of the lack of non-invasive cot-side monitors. This study aimed (i) to determine non-invasive monitoring tools of cerebral metabolism and perfusion by combining near-infrared spectroscopy and echocardiography, and (ii) to investigate the dependence of brain temperature on cerebral metabolism and perfusion in unsedated newborn infants. Thirty-two healthy newborn infants were recruited. They were studied with cerebral near-infrared spectroscopy, echocardiography, and a zero-heat flux tissue thermometer. A surrogate of cerebral blood flow (CBF) was measured using superior vena cava flow adjusted for cerebral volume (rSVC flow). The tissue oxygenation index, fractional oxygen extraction (FOE), and the cerebral metabolic rate of oxygen relative to rSVC flow (CMRO2 index) were also estimated. A greater rSVC flow was positively associated with higher brain temperatures, particularly for superficial structures. The CMRO2 index and rSVC flow were positively coupled. However, brain temperature was independent of FOE and the CMRO2 index. A cooler ambient temperature was associated with a greater temperature gradient between the scalp surface and the body core. Cerebral oxygen metabolism and perfusion were monitored in newborn infants without using tracers. In these healthy newborn infants, cerebral perfusion and ambient temperature were significant independent variables of brain temperature. CBF has primarily been associated with heat removal from the brain. However, our results suggest that CBF is likely to deliver heat specifically to the superficial brain. Further studies are required to assess the effect of cerebral metabolism and perfusion on regional brain temperature in low-cardiac output conditions, fever, and with therapeutic hypothermia