Ministry of Education, Culture, Sports, Science and Technology

Neural progenitor cells, including neural stem cells, are a potential expandable source of graft material for transplantation aimed at repairing the damaged CNS. Here we present the first evidence that in vitro-expanded fetus-derived neurosphere cells were able to generate neurons in vivo and improve motor function upon transplantation into an adult rat spinal-cord-contusion injury model. As the source of graft material, we used a neural stem cell-enriched population that was derived from rat embryonic spinal cord (E14.5) and expanded in vitro by neurosphere formation. Nine days after contusion injury, these neurosphere cells were transplanted into adult rat spinal cord at the injury site. Histological analysis 5 weeks after the transplantation showed that mitotic neurogenesis occurred from the transplanted donor progenitor cells within the adult rat spinal cord, a nonneurogenic region; that these donor-derived neurons extended their processes into the host tissues; and that the neurites formed synaptic structures. Furthermore, analysis of motor behavior using a skilled reaching task indicated that the treated rats showed functional recovery. These results indicate that in vitro-expanded neurosphere cells derived from the fetal spinal cord are a potential source for transplantable material for treatment of spinal cord injury.

This treatise is an update to a preceding highlight (CH/π hydrogen bonds in crystals) published in this journal 5 years ago (M. Nishio, CrystEngComm, 2004, 6, 130–156). After the introductory part (sections 1 and 2), we survey recent results (mostly since 2004) relevant to the CH/π hydrogen bond: crystal conformation, packing and host/guest chemistry (section 3). Section 4 summarizes the results obtained by crystallographic database (CSD and PDB) analyses. In section 5, several topics in related fields (selectivity in organic reactions, surface chemistry, structural biology, drug design and high-level ab initio calculations of protein/substrate complexes and natural organic compounds) are introduced, and in the final part we comment on the prospects of this emerging field of chemistry.

A nuclidic mass formula composed of a gross term, an even-odd term and a shell term is presented as a revised version of the mass formula constructed by the present authors and published in 2000. The gross term has almost the same functional form as in the previous formula, but the parameter values in it are somewhat different. The even-odd term is treated more carefully, and a considerable improvement is realized. The shell term is exactly the same as the previous one; it was obtained using spherical single-particle potentials and by treating the deformed nucleus as a superposition of spherical nuclei. The new mass formula is applicable to nuclei with Z 2 and N 2. The root-mean-square deviation from experimental masses is 666.7 keV, which is less than that of the previous mass formula, 689.8 keV.

We developed a new endoscopic thyroid surgery by the axillo-bilateral-breast approach (ABBA) method, which is different from the previously described breast approach (BA) in that the port sites are modified to obtain a better view and to prevent the interference of surgical instruments. This modification also improves cosmetic results by eliminating the parasternal incision, which results in hypertrophic scar in a significant number of cases treated with BA. Twelve patients with benign thyroid tumors successfully underwent endoscopic thyroid surgery by ABBA, and their clinical outcomes were compared with those of four patients treated with BA. The mean operation time was significantly shorter in the ABBA group than in the BA group (188 minutes vs. 270 minutes; P < 0.01). Furthermore, the mean blood loss in the ABBA group (53 mL) was half of that in the BA group (108 mL). Neither conversion to open surgery nor significant intraoperative complications were experienced. The operative scars by ABBA became inconspicuous in a few weeks. These results seem to indicate that ABBA is a better method than BA and can be a feasible option, particularly for young patients who opt for the better cosmetic outcome.

BACKGROUND AND PURPOSE: The necessity for structural MRI is greater than ever to both diagnose AD in its early stage and objectively evaluate its progression. We propose a new VBM-based software program for automatic detection of early specific atrophy in AD. MATERIALS AND METHODS: A target VOI was determined by group comparison of 30 patients with very mild AD and 40 age-matched healthy controls by using SPM. Then this target VOI was incorporated into a newly developed automated software program independently running on a Windows PC for VBM by using SPM8 plus DARTEL. ROC analysis was performed for discrimination of 116 other patients with AD with very mild stage (n = 45), mild stage (n = 30) and moderate-to-advanced stages (n = 41) from 40 other age-matched healthy controls by using a z score map in the target VOI. RESULTS: Medial temporal structures involving the entire region of the entorhinal cortex, hippocampus, and amygdala showed significant atrophy in the patients with very mild AD and were determined as a target VOI. When we used the severity score of atrophy in this target VOI, 91.6%, 95.8%, and 98.2% accuracies were obtained in the very mild AD, mild AD, and moderate-to-severe AD groups, respectively. In the very mild AD group, a high specificity of 97.5% with a sensitivity of 86.4% was obtained, and age at onset of AD did not influence this accuracy. CONCLUSIONS: This software program with application of SPM8 plus DARTEL to VBM provides a high performance for AD diagnosis by using MRI.

Since the first report of serum IgG4 elevation in sclerosing pancreatitis in 2001, various systemic disorders have been reported to elevate IgG4, and many names have been proposed from the perspective of the systemic condition. Despite similarities in the organs damaged in IgG4-related Mikulicz's disease and Sjögren's syndrome, there are marked clinical and pathological differences between the 2 entities. The majority of cases diagnosed with autoimmune pancreatitis in Japan are IgG4-related sclerosing pancreatitis, and it should be recognized that this is distinct from the Western type. Diagnosis of IgG4-related disease is defined by both elevated serum IgG4 (> 1.35 g/l) and histopathological features, including lymphocyte and IgG4+ plasma cell infiltration (IgG4+ plasma cells/IgG+ plasma cells > 50% on a highly magnified slide checked at 5 points). Differential diagnosis from other distinct disorders is necessary: these include sarcoidosis, Castleman's disease, Wegener's granulomatosis, lymphoma, cancer, and other existing conditions. The Japanese IgG4 research group has begun multicenter prospective studies to improve diagnostic criteria and treatment strategies.

Abstract Noise‐based crustal seismic velocity changes are known to be affected by environmental perturbations, such as rainfall, atmospheric pressure loading, and temperature changes. Similar to geodetic observations, these external perturbations can mask the effects of tectonic and volcanic processes. In this study, we benefit from the dense Hi‐net short‐period seismic network that covers the entire Japan to measure continuous changes in seismic velocities over a few years, using noise‐based seismic monitoring. Some strong seasonal seismic velocity changes are observed in both southern Japan (Kyushu Island) and northern Japan (Hokkaido Island). Decreasing of seismic velocities in summer in southern Japan can be clearly explained by a model of increased crustal fluid pore pressure associated with high rainfall. In northern Japan, it is necessary to adopt a more complex model to explain the observed seismic velocity variations, which takes into account precipitation, snow depth, and sea level changes. Moreover, western and eastern Hokkaido Island show very different responses to these different external perturbations. The models developed are used to remove the seasonal components of the seismic velocity changes. The minimum remaining detectable seismic velocity change reduces to 10 −5 , which allows detection of crustal responses to small earthquakes that are previously hidden in the strong seasonal perturbations.

Abstract Addressing many of the world’s contemporary challenges requires a multifaceted and integrated approach, and interdisciplinary research (IDR) has become increasingly central to both academic interest and government science policies. Although higher interdisciplinarity is then often assumed to be associated with higher research impact, there has been little solid scientific evidence supporting this assumption. Here, we provide verifiable evidence that interdisciplinarity is statistically significantly and positively associated with research impact by focusing on highly cited paper clusters known as the research fronts (RFs). Interdisciplinarity is uniquely operationalised as the effective number of distinct disciplines involved in the RF, computed from the relative abundance of disciplines and the affinity between disciplines, where all natural sciences are classified into eight disciplines. The result of a multiple regression analysis ( n = 2,560) showed that an increase by one in the effective number of disciplines was associated with an approximately 20% increase in the research impact, which was defined as a field-normalised citation-based measure. A new visualisation technique was then applied to identify the research areas in which high-impact IDR is underway and to investigate its evolution over time and across disciplines. Collectively, this work establishes a new framework for understanding the nature and dynamism of IDR in relation to existing disciplines and its relevance to science policymaking.

Mesencephalic precursor cells may one day provide dopaminergic neurons for the treatment of Parkinson's disease. However, the generation of dopaminergic neurons from mesencephalic precursors has been difficult to follow, partly because an appropriate means for recognizing mesencephalic ventricular zone precursors has not been available. To visualize and isolate mesencephalic precursor cells from a mixed population, we used transgenic mice and rats carrying green fluorescent protein ( GFP ) cDNA under the control of the nestin enhancer. nestin -driven GFP was detected in the mesencephalic ventricular zone, and it colocalized with specific markers for neural precursor cells. In addition, data from flow-cytometry indicated that Prominin/CD133, a cell-surface marker for ventricular zone cells, was expressed specifically in these GFP-positive (GFP + ) cells. After sorting by fluorescence-activated cell sorting, the GFP + cells proliferated in vitro and expressed precursor cell markers but not neuronal markers. Using clonogenic sphere formation assays, we showed that this sorted population was enriched in multipotent precursor cells that could differentiate into both neurons and glia. Importantly, many neurons generated from nestin-GFP -sorted mesencephalic precursors developed a dopaminergic phenotype in vitro . Finally, nestin-GFP + cells were transplanted into the striatum of a rat model of Parkinson's disease. Bromodeoxyuridine–tyrosine hydroxylase double-labeling revealed that the transplanted cells generated new dopaminergic neurons within the host striatum. The implanted cells were able to restore dopaminergic function in the host striatum, as assessed by a behavioral measure: recovery from amphetamine-induced rotation. Together, these findings indicate that precursor cells harvested from the embryonic ventral mesencephalon can generate dopaminergic neurons able to restore function to the chemically denervated adult striatum.

Nop56p is a component of the box C/D small nucleolar ribonucleoprotein complexes that direct 2'-O-methylation of pre-rRNA during its maturation. Genetic analyses in yeast have shown that Nop56p plays important roles in the early steps of pre-rRNA processing. However, its precise function remains elusive, especially in higher eukaryotes. Here we describe the proteomic characterization of human Nop56p (hNop56p)-associated pre-ribosomal ribonucleoprotein complexes. Mass spectrometric analysis of purified pre-ribosomal ribonucleoprotein complexes identified 61 ribosomal proteins, 16 trans-acting factors probably involved in ribosome biogenesis, and 29 proteins whose function in ribosome biogenesis is unknown. Identification of pre-rRNA species within hNop56p-associated pre-ribosomal ribonucleoprotein complexes, coupled with the known functions of yeast orthologs of the probable trans-acting factors identified in human, demonstrated that hNop56p functions in the early to middle stages of 60 S subunit synthesis in human cells. Interestingly, the nucleolar phosphoprotein treacle, which is responsible for the craniofacial disorder associated with Treacher Collins syndrome, was found to be a constituent of hNop56p-associated pre-rRNP complexes. The association of hNop56p and treacle within the complexes was independent of rRNA integrity, indicating a direct interaction. In addition, the protein compositions of the treacle-associated and hNop56p-associated pre-ribosomal ribonucleoprotein complexes were very similar, suggesting functional similarities between these two complexes with respect to ribosome biogenesis in human cells.

We present a determination of the gluon polarization Delta G/G in the nucleon, based on the helicity asymmetry of quasi-real photoproduction events, Q^2<1(GeV/c)^2, with a pair of large transverse-momentum hadrons in the final state. The data were obtained by the COMPASS experiment at CERN using a 160 GeV polarized muon beam scattered on a polarized 6-LiD target. The helicity asymmetry for the selected events is <A_||/D> = 0.002 +- 0.019(stat.) +- 0.003(syst.). From this value, we obtain in a leading-order QCD analysis Delta G/G=0.024 +- 0.089(stat.) +- 0.057(syst.) at x_g = 0.095 and mu^2 =~ 3 (GeV}/c)^2.

Research Article| January 23, 2018 The Propagation of Local Undamped Motion (PLUM) Method: A Simple and Robust Seismic Wavefield Estimation Approach for Earthquake Early Warning Yuki Kodera; Yuki Kodera aMeteorological Research Institute, Japan Meteorological Agency, 1‐1 Nagamine, Tsukuba, Ibaraki 305‐0052, Japan, y_kodera@mri-jma.go.jp, ktamarib@mri-jma.go.jp, mhoshiba@mri-jma.go.jp Search for other works by this author on: GSW Google Scholar Yasuyuki Yamada; Yasuyuki Yamada bSeismology and Volcanology Department, Japan Meteorological Agency, 1‐3‐4 Otemachi, Chiyoda‐ku, Tokyo 100‐8122, Japan, yamada1228@met.kishou.go.jp, sh_adachi@met.kishou.go.jp, hayashimoto@met.kishou.go.jp, morimoto.masahiko@met.kishou.go.jp Search for other works by this author on: GSW Google Scholar Kazuyuki Hirano; Kazuyuki Hirano cOsaka Regional Headquarter, Japan Meteorological Agency, 4‐1‐76 Otemae, Chuo‐ku, Osaka 540‐0008, Japan, k-hirano@met.kishou.go.jp Search for other works by this author on: GSW Google Scholar Koji Tamaribuchi; Koji Tamaribuchi aMeteorological Research Institute, Japan Meteorological Agency, 1‐1 Nagamine, Tsukuba, Ibaraki 305‐0052, Japan, y_kodera@mri-jma.go.jp, ktamarib@mri-jma.go.jp, mhoshiba@mri-jma.go.jp Search for other works by this author on: GSW Google Scholar Shimpei Adachi; Shimpei Adachi bSeismology and Volcanology Department, Japan Meteorological Agency, 1‐3‐4 Otemachi, Chiyoda‐ku, Tokyo 100‐8122, Japan, yamada1228@met.kishou.go.jp, sh_adachi@met.kishou.go.jp, hayashimoto@met.kishou.go.jp, morimoto.masahiko@met.kishou.go.jp Search for other works by this author on: GSW Google Scholar Naoki Hayashimoto; Naoki Hayashimoto bSeismology and Volcanology Department, Japan Meteorological Agency, 1‐3‐4 Otemachi, Chiyoda‐ku, Tokyo 100‐8122, Japan, yamada1228@met.kishou.go.jp, sh_adachi@met.kishou.go.jp, hayashimoto@met.kishou.go.jp, morimoto.masahiko@met.kishou.go.jp Search for other works by this author on: GSW Google Scholar Masahiko Morimoto; Masahiko Morimoto bSeismology and Volcanology Department, Japan Meteorological Agency, 1‐3‐4 Otemachi, Chiyoda‐ku, Tokyo 100‐8122, Japan, yamada1228@met.kishou.go.jp, sh_adachi@met.kishou.go.jp, hayashimoto@met.kishou.go.jp, morimoto.masahiko@met.kishou.go.jp Search for other works by this author on: GSW Google Scholar Masaki Nakamura; Masaki Nakamura dResearch and Development Bureau, Ministry of Education, Culture, Sports, Science and Technology, 3‐2‐2 Kasumigaseki, Chiyoda‐ku, Tokyo 100‐8959, Japan, mnakamur@mext.go.jp Search for other works by this author on: GSW Google Scholar Mitsuyuki Hoshiba Mitsuyuki Hoshiba aMeteorological Research Institute, Japan Meteorological Agency, 1‐1 Nagamine, Tsukuba, Ibaraki 305‐0052, Japan, y_kodera@mri-jma.go.jp, ktamarib@mri-jma.go.jp, mhoshiba@mri-jma.go.jp Search for other works by this author on: GSW Google Scholar Bulletin of the Seismological Society of America (2018) 108 (2): 983–1003. https://doi.org/10.1785/0120170085 Article history first online: 23 Jan 2018 Cite View This Citation Add to Citation Manager Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Search Site Citation Yuki Kodera, Yasuyuki Yamada, Kazuyuki Hirano, Koji Tamaribuchi, Shimpei Adachi, Naoki Hayashimoto, Masahiko Morimoto, Masaki Nakamura, Mitsuyuki Hoshiba; The Propagation of Local Undamped Motion (PLUM) Method: A Simple and Robust Seismic Wavefield Estimation Approach for Earthquake Early Warning. Bulletin of the Seismological Society of America 2018;; 108 (2): 983–1003. doi: https://doi.org/10.1785/0120170085 Download citation file: Ris (Zotero) Refmanager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentBy SocietyBulletin of the Seismological Society of America Search Advanced Search Abstract A basic methodology for earthquake early warning is the use of point‐source models fed with observational data from triggered stations. The 2011 Off the Pacific Coast of Tohoku earthquake in Japan (⁠Mw 9.0) (the Tohoku‐Oki earthquake) and its aftershock and induced earthquake activity, however, highlighted the following technical challenges of point‐source models: (1) underprediction of the strong motion of large earthquakes with finite faults, (2) missing earthquakes during intense seismic activities, and (3) overprediction of the strong motion of multiple simultaneous earthquakes. We propose the propagation of local undamped motion (PLUM) method to address these technical challenges. The PLUM method is a simple wavefield‐estimation approach that predicts seismic intensities directly from observed real‐time seismic intensities near target sites. The PLUM method can outperform point‐source‐model approaches in terms of (a) accurate ground‐motion prediction for large earthquakes with finite faults and (b) robust event declaration for complex earthquake sequences. On the other hand, available warning times provided by the PLUM method are not expected to be very long. We also introduce a hybrid method that uses both the PLUM method and a point‐source‐model approach to maximize the total available warning times and avoid missing strong motion. When applied to the Tohoku‐Oki earthquake (⁠Mw 9.0), the PLUM and hybrid methods predicted accurate strong motion without underestimation and provided sufficient warning times in most areas. For the subsequent earthquake sequence after the Mw 9.0 earthquake, the PLUM method robustly detected and processed large earthquakes despite considerable intense seismicity. A statistical analysis using large aftershocks and induced earthquakes demonstrated that the PLUM and hybrid methods predicted strong motion more accurately than the point‐source‐model approach of the Japan Meteorological Agency. These findings indicate that the PLUM and hybrid methods can be effective countermeasures to address the technical challenges faced by point‐source models. You do not have access to this content, please speak to your institutional administrator if you feel you should have access.

We consider permanence of an SIR epidemic model with distributed time delays. Based on some known techniques on limit sets of differential dynamical systems, we show that, for any time delay, the SIR epidemic model is permanent if and only if an endemic equilibrium exits.

Staphylococcal enterotoxins (SEs) are a common causative agent of food poisoning. Recently, many new SE-like (SEl) toxins have been reported, although the role of SEls in food poisoning remains unclear. In this study, the emetic potentials of SElK, SElL, SElM, SElN, SElO, SElP, and SElQ were assessed using a monkey-feeding assay. All the SEls that were tested induced emetic reactions in monkeys at a dose of 100 μg/kg, although the numbers of affected monkeys were significantly smaller than the numbers that were affected after consuming SEA or SEB. This result suggests that these new SEs may play some role in staphylococcal food poisoning.

The safety and lack of undue operative stress on the donor are documented from an analysis of 100 parental donors, whose children (3 months to 17 years old), received LRLTx at our institution between June 1992 and May 1994. Survival rate of recipients was 86%. No primary nonfunctioning liver was observed. The donors were 56 mothers and 44 fathers. Their ages ranged from 19 to 51 years and their weight ranged from 44 to 80 kg. They received partial liver resections to harvest the grafts. With regard to the liver graft, the left lobe was used in 24 cases (group L) and the left lateral segment was used in 75 cases (group S). The right lobe was used in one case. In the two groups, blood losses were 242 +/- 5 (S) and 312 +/- 14 ml (L); operation times were 6.22 +/- 0.11 (S) and 7.15 +/- 0.21 hr (L), respectively; in both groups, the postoperative hospital stay was 11 days (S, L). No significant differences between the two groups were observed in peripheral RBC and WBC count or serum AST. An increase in total bilirubin was not observed. In the exceptional case using the right lobe, blood loss of 2300 ml necessitated a blood transfusion of 1000 ml, and the total bilirubin increased up to 4.0 mg/dl on the third postoperative day, which prolonged the postoperative hospital stay to 17 days. These results conclusively suggest that safety is guaranteed when the left lobe or the left lateral segment is used as the liver graft for LRLTx.

To evaluate the clinical and technical factors affecting the ability of fluorescence cholangiography (FC) using indocyanine green (ICG) to delineate the bile duct anatomy during laparoscopic cholecystectomy (LC).Application of FC during LC began after laparoscopic fluorescence imaging systems became commercially available.In 108 patients undergoing LC, FC was performed by preoperative intravenous injection of ICG (2.5 mg) during dissection of Calot's triangle, and clinical factors affecting the ability of FC to delineate the extrahepatic bile ducts were evaluated. Equipment-related factors associated with bile duct detectability were also assessed among 5 laparoscopic systems and 1 open fluorescence imaging system in ex vivo studies.FC delineated the confluence between the cystic duct and common hepatic duct (CyD-CHD) before and after dissection of Calot's triangle in 80 patients (74%) and 99 patients (92%), respectively. The interval between ICG injection and FC before dissection of Calot's triangle was significantly longer in the 80 patients in whom the CyD-CHD confluence was detected by fluorescence imaging before dissection (median, 90 min; range, 15-165 min) than in the remaining 28 patients in whom the confluence was undetectable (median, 47 min; range, 21-205 min; P < 0.01). The signal contrast on the fluorescence images of the bile duct samples was significantly different among the laparoscopic imaging systems and tended to decrease more steeply than those of the open imaging system as the target-laparoscope distance increased and porcine tissues covering the samples became thicker.FC is a simple navigation tool for obtaining a biliary roadmap to reach the "critical view of safety" during LC. Key factors for better bile duct identification by FC are administration of ICG as far in advance as possible before surgery, sufficient extension of connective tissues around the bile ducts, and placement of the tip of laparoscope close and vertically to Calot's triangle.

STUDY DESIGN: This in vitro study clarifies the role of nitric oxide (NO) in human lumbar intervertebral disc metabolism. OBJECTIVE: To investigate the effects of NO on proteoglycan synthesis in human lumbar discs and to test the hypothesis that NO is a mediator of the changes in proteoglycan synthesis in response to hydrostatic pressure. SUMMARY OF BACKGROUND DATA: The authors have clarified that hydrostatic pressure has an apparent effect on proteoglycan synthesis as well as matrix metalloproteinase production in the intervertebral disc. The cellular mechanisms underlying the response of disc cells to hydrostatic pressure remain to be clarified. Herniated lumbar discs produce NO in response to interleukin (IL)-1 beta. In articular cartilage, NO mediates the change of proteoglycan synthesis by IL-1 or shear stress. METHODS: Fifty-eight lumbar intervertebral disc specimens were obtained from patients who had undergone posterior discectomy. The specimens were chopped into 1-2-mm cubes and were incubated in a plastic syringe with 1 mL Dulbecco's modified Eagle's medium (DMEM). The syringes were placed in a water-filled pressure vessel kept at 37 C. Hydrostatic pressures of 1 (control), 3, and 30 atmospheres (atm) were applied. Proteoglycan synthesis was determined from (35)S-sulfate incorporation rates. Nitrite (the stable oxidation product of NO) concentration in DMEM was determined by a spectrophotometric method based on the Griess reaction. As a competitive inhibitor of NO synthases, N(G)-methyl-l-arginine (l-NMA, 10-1000 micromol) and as an organic donor of NO, S-nitroso-N-acetylpenicillamine (SNAP, 1-200 micromol) were used. RESULTS: Addition of l-NMA suppressed NO production and increased proteoglycan synthesis rates in the intervertebral disc specimens in a dose-dependent fashion. Addition of SNAP increased exogenous NO content in the medium significantly and suppressed proteoglycan synthesis rates in a dose-dependent fashion. Three-atmosphere hydrostatic pressure stimulated the proteoglycan synthesis rates. Rates were approximately 1.3-fold greater than at 1 atm, whereas 30-atm pressure inhibited proteoglycan synthesis rates. However, the hydrostaticpressure had inverse effect on NO production. At 3 atm, NO production decreased slightly relative to 1 atm, whereas at a pressure of 30 atm, NO production was increased and was approximately 1.32-fold greater than at 1 atm. L-NMA enhanced the 3-atm pressure-induced increase in proteoglycan synthesis and also relieved the suppression of proteoglycan synthesis at a pressure of 30 atm. CONCLUSION: The current study confirmed the previous finding that human herniated lumbar disc cultures spontaneously produce NO. Endogenously generated and exogenously supplied NO inhibited proteoglycan synthesis in the intervertebral disc. Hydrostatic pressure influenced NO production by disc cells, and NO is one of the mediators that changes proteoglycan synthesis in response to hydrostatic pressure. These results may show that autocrine and paracrine mechanisms of NO play an important role in the regulation of disc cell metabolism under mechanical stress and in the pathophysiology of intervertebral disc degeneration.

Neuropathic pain is the most difficult type of pain to control, and patients lose their motivation for the purposive pursuit with a decrease in their quality of life. Using a functional magnetic resonance imaging analysis, we demonstrated that blood oxygenation level-dependent signal intensity was increased in the ipsilateral nucleus accumbens (N.Acc.) following peripheral nerve injury. microRNAs are small, noncoding RNA molecules that direct the post-transcriptional suppression of gene expression, and play an important role in regulating synaptic plasticity. In this study, we found that sciatic nerve ligation induced a drastic decrease in the expression of miR200b and miR429 in N.Acc. neurons. The expression of DNA methyltransferase 3a (DNMT3a), which is the one of the predicted targets of miR200b/429, was significantly increased in the limbic forebrain including N.Acc. at 7 d after sciatic nerve ligation. Double-immunolabeling with antibodies specific to DNMT3a and NR1 showed that DNMT3a-immunoreactivity in the N.Acc. was located in NR1-labeled neurons, indicating that increased DNMT3a proteins were dominantly expressed in postsynaptic neurons in the N.Acc. area under a neuropathic pain-like state. The results of these analyses provide new insight into an epigenetic modification that is accompanied by a dramatic decrease in miR200b and miR429 along with the dysfunction of "mesolimbic motivation/valuation circuitry" under a neuropathic pain-like state. These phenomena may result in an increase in DNMT3a in neurons of the N.Acc. under neuropathic pain, which leads to the long-term transcription-silencing of several genes.

Miyata, Akinori MD; Ishizawa, Takeaki MD, PhD, FACS; Tani, Keigo MD; Shimizu, Atsushi MD, PhD; Kaneko, Junichi MD, PhD; Aoki, Taku MD, PhD; Sakamoto, Yoshihiro MD, PhD; Sugawara, Yasuhiko MD, PhD; Hasegawa, Kiyoshi MD, PhD, FACS; Kokudo, Norihiro MD, PhD, FACS Author Information

We have investigated the possible involvement of the ubiquitin-proteasome system (UPS) in ribosome biogenesis. We find by immunofluorescence that ubiquitin is present within nucleoli and also demonstrate by immunoprecipitation that complexes associated with pre-rRNA processing factors are ubiquitinated. Using short proteasome inhibition treatments, we show by fluorescence microscopy that nucleolar morphology is disrupted for some but not all factors involved in ribosome biogenesis. Interference with proteasome degradation also induces the accumulation of 90S preribosomes, alters the dynamic properties of a number of processing factors, slows the release of mature rRNA from the nucleolus, and leads to the depletion of 18S and 28S rRNAs. Together, these results suggest that the UPS is probably involved at many steps during ribosome biogenesis, including the maturation of the 90S preribosome.