Existence of phosphoinositide-specific phospholipase C in rat liver nuclei and its change during liver regeneration.

We found phosphoinositide-specific phospholipase C (PtdIns-PLC) activity in nuclei isolated from rat liver. The enzyme hydrolyzed phosphatidylinositol, phosphatidylinositol 4-monophosphate (PIP) and phosphatidylinositol 4,5-bisphosphate in a Ca(2+)-dependent manner, and produced inositol mono-, bis-, and triphosphate, respectively. Neither phosphatidylcholine, phosphatidylethanolamine, nor phosphatidylserine was utilized as a substrate. After partial hepatectomy, the PtdIns-PLC activity in isolated nuclei increased transiently in the S phase (20-22 h post-hepatectomy), to 2.5-fold higher than in the control, when measured with PIP. This result suggests a close relationship between the nuclear PtdIns-PLC, especially its PIP-hydrolyzing activity, and cell proliferation.     

Lung dosimetry of inhaled radon progeny in mice

Biological response of exposure to radon progeny has long been investigated, but there are only few studies in which absorbed doses in lungs of laboratory animals were estimated. The present study is the first attempt to calculate the doses of inhaled radon progeny for mice. For reference, the doses for rats and humans were also computed with the corresponding models. Lung deposition of particles, their clearance, and energy deposition of alpha particles to sensitive tissues were systematically simulated. Absorbed doses to trachea and bronchi, bronchioles and terminal bronchioles, alveolar-interstitial regions, and whole lung were first provided as a function of monodisperse radon progeny particles with an equilibrium equivalent radon concentration of 1?Bq?m^?3 (equilibrium factor, 0.4 and unattached fraction, 0.01). Based on the results, absorbed doses were then calculated for (1) a reference mine condition and (2) a condition previously used for animal experiments. It was found that the whole lung doses for mice, rats, and humans were 34.8, 20.7, and 10.7?nGy (Bq?m^?3)^?1?h^?1 for the mine condition, respectively, while they were 16.9, 9.9, and 6.5?nGy (Bq?m^?3)^?1?h^?1 for the animal experimental condition. In both cases, the values for mice are about 2 times higher than those for rats, and about 3 times higher than those for humans. Comparison of our data on rats and humans with those published in the literature shows an acceptable agreement, suggesting the validity of the present modeling for mice. In the future, a more sophisticated dosimetric study of inhaled radon progeny in mice would be desirable to demonstrate how anatomical, physiological, and environmental parameters can influence absorbed doses.     

Temporal Dynamics of Visual Attention Measured with Event-Related Potentials

How attentional modulation on brain activities determines behavioral performance has been one of the most important issues in cognitive neuroscience. This issue has been addressed by comparing the temporal relationship between attentional modulations on neural activities and behavior. Our previous study measured the time course of attention with amplitude and phase coherence of steady-state visual evoked potential (SSVEP) and found that the modulation latency of phase coherence rather than that of amplitude was consistent with the latency of behavioral performance. In this study, as a complementary report, we compared the time course of visual attention shift measured by event-related potentials (ERPs) with that by target detection task. We developed a novel technique to compare ERPs with behavioral results and analyzed the EEG data in our previous study. Two sets of flickering stimulus at different frequencies were presented in the left and right visual hemifields, and a target or distracter pattern was presented randomly at various moments after an attention-cue presentation. The observers were asked to detect targets on the attended stimulus after the cue. We found that two ERP components, P300 and N2pc, were elicited by the target presented at the attended location. Time-course analyses revealed that attentional modulation of the P300 and N2pc amplitudes increased gradually until reaching a maximum and lasted at least 1.5 s after the cue onset, which is similar to the temporal dynamics of behavioral performance. However, attentional modulation of these ERP components started later than that of behavioral performance. Rather, the time course of attentional modulation of behavioral performance was more closely associated with that of the concurrently recorded SSVEPs analyzed. These results suggest that neural activities reflected not by either the P300 or N2pc, but by the SSVEPs, are the source of attentional modulation of behavioral performance.     

A horse's eye view: size and shape discrimination compared with other mammals

Mammals have adapted to a variety of natural environments from underwater to aerial and these different adaptations have affected their specific perceptive and cognitive abilities. This study used a computer-controlled touchscreen system to examine the visual discrimination abilities of horses, particularly regarding size and shape, and compared the results with those from chimpanzee, human and dolphin studies. Horses were able to discriminate a difference of 14% in circle size but showed worse discrimination thresholds than chimpanzees and humans; these differences cannot be explained by visual acuity. Furthermore, the present findings indicate that all species use length cues rather than area cues to discriminate size. In terms of shape discrimination, horses exhibited perceptual similarities among shapes with curvatures, vertical/horizontal lines and diagonal lines, and the relative contributions of each feature to perceptual similarity in horses differed from those for chimpanzees, humans and dolphins. Horses pay more attention to local components than to global shapes.     

Site-specific Inhibitory Mechanism for Amyloid β42 Aggregation by Catechol-type Flavonoids Targeting the Lys Residues

The aggregation of the 42-residue amyloid β-protein (Aβ42) is involved in the pathogenesis of Alzheimer disease (AD). Numerous flavonoids exhibit inhibitory activity against Aβ42 aggregation, but their mechanism remains unclear in the molecular level. Here we propose the site-specific inhibitory mechanism of (+)-taxifolin, a catechol-type flavonoid, whose 3′,4′-dihydroxyl groups of the B-ring plays a critical role. Addition of sodium periodate, an oxidant, strengthened suppression of Aβ42 aggregation by (+)-taxifolin, whereas no inhibition was observed under anaerobic conditions, suggesting the inhibition to be associated with the oxidation to form o-quinone. Because formation of the Aβ42-taxifolin adduct was suggested by mass spectrometry, Aβ42 mutants substituted at Arg⁵, Lys¹⁶, and/or Lys²⁸ with norleucine (Nle) were prepared to identify the residues involved in the conjugate formation. (+)-Taxifolin did not suppress the aggregation of Aβ42 mutants at Lys¹⁶ and/or Lys²⁸ except for the mutant at Arg⁵. In addition, the aggregation of Aβ42 was inhibited by other catechol-type flavonoids, whereas that of K16Nle-Aβ42 was not. In contrast, some non-catechol-type flavonoids suppressed the aggregation of K16Nle-Aβ42 as well as Aβ42. Furthermore, interaction of (+)-taxifolin with the β-sheet region in Aβ42 was not observed using solid-state NMR unlike curcumin of the non-catechol-type. These results demonstrate that catechol-type flavonoids could specifically suppress Aβ42 aggregation by targeting Lys residues. Although the anti-AD activity of flavonoids has been ascribed to their antioxidative activity, the mechanism that the o-quinone reacts with Lys residues of Aβ42 might be more intrinsic. The Lys residues could be targets for Alzheimer disease therapy.     

Effect of addition of organic waste on reduction of Escherichia coli during cattle feces composting under high-moisture condition

To ensure Escherichia coli reduction during cattle feces composting, co-composting with a variety of organic wastes was examined. A mixture of dairy cattle feces and shredded rice straw (control) was blended with organic wastes (tofu residue, rice bran, rapeseed meal, dried chicken feces, raw chicken feces, or garbage), and composted using a bench-scale composter under the high-moisture condition (78%). The addition of organic waste except chicken feces brought about maximum temperatures of more than 55 degrees C and significantly reduced the number of E. coli from 10(6) to below 10(2)CFU/g-wet after seven days composting, while in the control treatment, E. coli survived at the same level as that of raw feces. Enhancements of the thermophilic phase and E. coli reduction were related to the initial amount of easily digestible carbon in mass determined as BOD. BOD value more than 166.2 mg O2/DMg brought about significant E. coli reduction.     

A novel branching enzyme of the GH-57 family in the hyperthermophilic archaeon Thermococcus kodakaraensis KOD1

Branching enzyme (BE) catalyzes formation of the branch points in glycogen and amylopectin by cleavage of the alpha-1,4 linkage and its subsequent transfer to the alpha-1,6 position. We have identified a novel BE encoded by an uncharacterized open reading frame (TK1436) of the hyperthermophilic archaeon Thermococcus kodakaraensis KOD1. TK1436 encodes a conserved protein showing similarity to members of glycoside hydrolase family 57 (GH-57 family). At the C terminus of the TK1436 protein, two copies of a helix-hairpin-helix (HhH) motif were found. TK1436 orthologs are distributed in archaea of the order Thermococcales, cyanobacteria, some actinobacteria, and a few other bacterial species. When recombinant TK1436 protein was incubated with amylose used as the substrate, a product peak was detected by high-performance anion-exchange chromatography, eluting more slowly than the substrate. Isoamylase treatment of the reaction mixture significantly increased the level of short-chain alpha-glucans, indicating that the reaction product contained many alpha-1,6 branching points. The TK1436 protein showed an optimal pH of 7.0, an optimal temperature of 70 degrees C, and thermostability up to 90 degrees C, as determined by the iodine-staining assay. These properties were the same when a protein devoid of HhH motifs (the TK1436DeltaH protein) was used. The average molecular weight of branched glucan after reaction with the TK1436DeltaH protein was over 100 times larger than that of the starting substrate. These results clearly indicate that TK1436 encodes a structurally novel BE belonging to the GH-57 family. Identification of an overlooked BE species provides new insights into glycogen biosynthesis in microorganisms.     

Basic study on biochemical mechanism of thoron and thermal therapy

Exposure to water in hot springs containing thoron is thought to exercise beneficial effects on hypertension and diabetes mellitus. To put to a test this hypothesis we examined the time dependent changes in the levels of lipid peroxide, vasoactive- and diabetes associated substances in human blood in order to throw further light on the possible beneficial influence of thoron and thermal therapy on the mechanism of hypertension and diabetes mellitus. Every 2 days, nasal inhalation of vapor containing thoron was performed for 40 min. Blood samples were collected after each treatment at 1, 2, and 3 weeks after the first treatment. Results show that the treatment decreased the lipid peroxide levels. The finding suggests that the treatment contributes to the prevention of peroxidation reaction related to hypertension and diabetes mellitus. Moreover, the changes in vasoactive-associated substances indicate an increase in tissue perfusion, suggesting that the treatment plays a role in alleviating hypertension. The treatment decreased the total ketone body levels and the finding suggests that the treatment contributes to the prevention of diabetes mellitus related to the insulin deficiency.     

Histological changes in spleens of radio-sensitive and radio-resistant mice exposed to low-dose X-ray irradiation

We have previously determined by using immune-assay or bio-assay methods that low-dose irradiation enhances immune and anti-oxidation functions. In this study, we examined histological changes of lymphatic follicles at 4, 24, or 48 hrs after sham, 0.25, 0.5, or 15 Gy irradiation in the spleens of BALB/c mice, which are sensitive to radiation compared with other strains, and C57BL/6J mice, which are resistant to radiation, using hematoxylin-eosin staining for lymphatic follicles or methylgreen pyronin staining for plasma cells. Results show that the lymphatic follicles in the spleens of the two mouse strains decreased at 24 or 48 hrs after 15 Gy irradiation. The number of plasma cells in the spleens of sham irradiated BALB/c mice was greater than that of sham irradiated C57BL/6J mice. At 4 hrs after 0.25 Gy irradiation, plasma cells increased in the spleens of the two mouse strains. These findings suggest, by histology, that low-dose irradiation activates the plasma cells and enhances the immune function. Although those two mouse strains have different sensitivities to radiation, the above changes were similar in both time course and degree of response. Therefore, the phenomena observed may be common in mice.