Intranuclear topological distribution of HIV-1 trans-activators

AbstractSubcellular localization of human immunodeficiency virus type 1 (HIV-1) Tat and Rev was examined using a confocal laser scanning microscope (CLSM). In transfected COS-7 cells, Tat resided exclusively in the perinocleolar region, while Rev infiltrated fully into the nucleoli. The chimeric Tat in which the nucleolar targeting signal was replaced by that of Rev, which retains trans-acting activity of Tat, remained still in the perinucleolar region as wild-type Tat. Perinucleolar distribution of Tat protein suggests the existence of a novel nucleolar architecture that affects transcription

Carbenoxolone-sensitive and cesium-permeable potassium channel in the rod cells of frog taste discs

The rod cells in frog taste discs display the outward current and maintain the negative resting potential in the condition where internal K+ is replaced with Cs+. We analyzed the properties of the Cs+-permeable conductance in the rod cells. The current-voltage (I/V) relationships obtained by a voltage ramp were bell-shaped under Cs+ internal solution. The steady state I/V relationships elicited by voltage steps also displayed the bell-shaped outward current. The activation of the current accelerated with the depolarization and the inactivation appeared at positive voltage. The gating for the current was maintained even at symmetric condition (Cs+ external and internal solutions). The wing cells did not show the properties. The permeability for K+ was a little larger than that for Cs+. Internal Na+ and NMDG+ could not induce the bell-shaped outward current. Carbenoxolone inhibited the bell-shaped outward Cs+ current dose dependently (IC50: 27μM). Internal arachidonic acid (20μM) did not induce the linear current-voltage (I-V) relationship which is observed in two-pore domain K+ channel (K2P). The results suggest that the resting membrane potentials in the rod cells are maintained by the voltage-gated K+ channels

ミズ ヲ リヨウシタ ウチュウセン チュウセイシ カンソク ソウチ

当初,南極観測用に製作された宇宙線中性子観測装置は,IGY用として設計されたもので,全体の重量が6トンを超えるため,ヘリコプター輸送に適さない.そこで重量軽減化の方法として,(1)ニュートロン減速剤として,パラフィンの代りに現地の海水を利用する.(2)真空管方式の増幅,計数装流をすべてトランジスター化する.の2点から,新しい観測装置を製作した.この装置は重量約500kgで,第4次観測隊により無事基地へ空輪された.観測は1960年3月3日より開始された.観測結果の一部として,日平均値の変化及び5月4日の宇宙線異常増加の結果を示した

CRMP5 (Collapsin Response Mediator Protein 5) Regulates Dendritic Development and Synaptic Plasticity in the Cerebellar Purkinje Cells

Collapsin response mediator protein 5 (CRMP5) is one of the CRMP members that expresses abundantly in the developing brain. To examine the in vivo function of CRMP5, we generated crmp5-deficient (crmp5(-/-)) mice. Anti-calbindin immunofluorescence studies of crmp5(-/-) mice revealed aberrant dendrite morphology; specifically, a decrease in the size of soma and diameter of primary dendrite of the cerebellar Purkinje cells at postnatal day 21 (P21) and P28, but not at P14. Coincidentally, CRMP5 is detected in Purkinje cells at P21 and P28 from crmp5(+/-) mice. In cerebellar slices of crmp5(-/-) mice, the induction of long-term depression of excitatory synaptic transmission between parallel fibers and Purkinje cells was deficient. Given that brain-derived neurotrophic factor (BDNF) plays major roles in dendritic development, we tried to elucidate the possible roles of CRMP5 in BDNF signaling. The effect of BDNF to induce dendritic branching was markedly attenuated in cultured crmp5(-/-) neurons. Furthermore, CRMP5 was tyrosine phosphorylated when coexpressed with neurotrophic tyrosine kinase receptor type 2 (TrkB), a receptor for BDNF, in HEK293T cells. These findings suggest that CRMP5 is involved in the development, maintenance and synaptic plasticity of Purkinje cells

Dental Calculus Stimulates Interleukin-1beta Secretion by Activating NLRP3 Inflammasome in Human and Mouse Phagocytes

Dental calculus is a mineralized deposit associated with periodontitis. The bacterial components contained in dental calculus can be recognized by host immune sensors, such as Toll-like receptors (TLRs), and induce transcription of proinflammatory cytokines, such as IL-1beta. Studies have shown that cellular uptake of crystalline particles may trigger NLRP3 inflammasome activation, leading to the cleavage of the IL-1beta precursor to its mature form. Phagocytosis of dental calculus in the periodontal pocket may therefore lead to the secretion of IL-1beta, promoting inflammatory responses in periodontal tissues. However, the capacity of dental calculus to induce IL-1beta secretion in human phagocytes has not been explored. To study this, we stimulated human polymorphonuclear leukocytes (PMNs) and peripheral blood mononuclear cells (PBMCs) with dental calculus collected from periodontitis patients, and measured IL-1beta secretion by ELISA. We found that calculus induced IL-1beta secretion in both human PMNs and PBMCs. Calculus also induced IL-1beta in macrophages from wild-type mice, but not in macrophages from NLRP3- and ASC-deficient mice, indicating the involvement of NLRP3 and ASC. IL-1beta induction was inhibited by polymyxin B, suggesting that LPS is one of the components of calculus that induces pro-IL-1beta transcription. To analyze the effect of the inorganic structure, we baked calculus at 250 degrees C for 1 h. This baked calculus failed to induce pro-IL-1beta transcription. However, it did induce IL-1beta secretion in lipid A-primed cells, indicating that the crystalline structure of calculus induces inflammasome activation. Furthermore, hydroxyapatite crystals, a component of dental calculus, induced IL-1beta in mouse macrophages, and baked calculus induced IL-1beta in lipid A-primed human PMNs and PBMCs. These results indicate that dental calculus stimulates IL-1beta secretion via NLRP3 inflammasome in human and mouse phagocytes, and that the crystalline structure has a partial role in the activation of NLRP3 inflammasome

Involvement of influx and efflux transport systems in gastrointestinal absorption of celiprolol

金沢大学医薬保健研究域薬学系Gastrointestinal absorption of several β-blockers is inhibited by citrus juices, although molecular mechanism(s) lying on their small intestinal absorption has not yet been identified. Here, we attempted to demonstrate involvement of both influx and efflux transporters in vivo in gastrointestinal absorption of celiprolol in mice. Plasma concentration of celiprolol (3 mg/kg) after oral administration was mostly under the limit of quantification in wild mice, whereas that in mdr1a/b knockout (mdr1a/b(-/-)) mice was much more obvious, indicating P-glycoprotein-mediated efflux. Then, the oral absorption of celiprolol in mdr1a/b(-/-) mice was further examined to investigate influx transport mechanism with avoiding effect of P-glycoprotein. Coadministration of bromosulfophthalein (BSP), an inhibitor of various influx transporters including organic anion transporting polypeptide (OATP) reduced plasma celiprolol concentration. Inhibition by BSP of celiprolol uptake from apical membranes was confirmed in Ussing-type chamber of small intestinal tissues. Uptake of celiprolol by human small intestinal transporter OATP-A/1A2 was also confirmed in Xenopus Laevis oocytes. Interestingly, OATP-A/1A2 accepts various b-blockers including acebutolol, atenolol and sotalol, oral absorption of which is inhibited by coadministration of citrus juice or telithromycin in human. Taken together, these findings have suggested fundamental role of influx transport system(s) in oral absorption of celiprolol. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association

Factors Affecting the Variation of Maximum Speech Intelligibility in Patients With Sensorineural Hearing Loss Other Than Apparent Retrocochlear Lesions

ObjectivesTo examine the relationship between speech intelligibilities among the similar level of hearing loss and threshold elevation of the auditory brainstem response (ABR).MethodsThe relationship between maximum speech intelligibilities among similar levels of hearing loss and relative threshold elevation of the click-evoked ABR (ABR threshold - pure tone average at 2,000 and 4,000 Hz) was retrospectively reviewed in patients with sensorineural hearing loss (SNHL) other than apparent retrocochlear lesions as auditory neuropathy, vestibular schwannoma and the other brain lesions.ResultsComparison of the speech intelligibilities in subjects with similar levels of hearing loss found that the variation in maximum speech intelligibility was significantly correlated with the threshold elevation of the ABR.ConclusionThe present results appear to support the idea that variation in maximum speech intelligibility in patients with similar levels of SNHL may be related to the different degree of dysfunctions of the inner hair cells and/or cochlear nerves in addition to those of outer hair cells