Serological Study of Bartonella henselae in Cat Scratch Disease in Japan

It has become clear that Bartonella henselae is a common cause of cat scratch disease (CSD). The indirect fluorescence antibody (IFA) test for detection of IgG and IgM antibodies to B. henselae concerning CSD showed that 5 (50%) of 10 patients with CSD had a serum IgG antibody titer of 1:128 or more and that 2 (20%) patients had a serum IgM antibody titer of 1:20 or more. One of 7 asymptomatic members of patients' families (14%) had IgG antibody to B. henselae at a titer of 1:256. IgM antibody to B. henselae was not detected in sera from the patients' families. Both IgG and IgM antibodies to B. henselae were not detected in sera from the healthy control group. These data suggest that B. henselae may be a cause of CSD in Japan.     

The combination of dimethoxycurcumin with DNA methylation inhibitor enhances gene re-expression of promoter-methylated genes and antagonizes their cytotoxic effect

Curcumin and its analogs exhibited antileukemic activity either as single agent or in combination therapy. Dimethoxycurcumin (DMC) is a more metabolically stable curcumin analog that was shown to induce the expression of promoter-methylated genes without reversing DNA methylation. Accordingly, co-treatment with DMC and DNA methyltransferase (DNMT) inhibitors could hypothetically enhance the re-expression of promoter-methylated tumor suppressor genes. In this study, we investigated the cytotoxic effects and epigenetic changes associated with the combination of DMC and the DNMT inhibitor decitabine (DAC) in primary leukemia samples and cell lines. The combination demonstrated antagonistic cytotoxic effects and was minimally cytotoxic to primary leukemia cells. The combination did not affect the metabolic stability of DMC. Although the combination enhanced the downregulation of nuclear DNMT proteins, the hypomethylating activity of the combination was not increased significantly compared to DAC alone. On the other hand, the combination significantly increased H3K27 acetylation (H3K27Ac) compared to the single agents near the promoter region of promoter-methylated genes. Furthermore, sequential chromatin immunoprecipitation (ChIP) and DNA pyrosequencing of the chromatin-enriched H3K27Ac did not show any significant decrease in DNA methylation compared to other regions. Consequently, the enhanced induction of promoter-methylated genes by the combination compared to DAC alone is mediated by a mechanism that involves increased histone acetylation and not through potentiation of the DNA hypomethylating activity of DAC. Collectively, our results provide the mechanistic basis for further characterization of this combination in leukemia animal models and early phase clinical trials.     

The Association of Childhood Fitness to Proactive and Reactive Action Monitoring

Several studies have claimed that the positive association between childhood fitness and cognitive control is attributable to differences in the child’s cognitive control strategy, which can involve either proactive or reactive control. The present study tested this hypothesis by manipulating the probability of trial types during a modified flanker task. Preadolescent children performed mostly congruent and mostly incongruent conditions of the flanker task, with post-error task performance and error negativity/error-related negativity (Ne/ERN) being assessed. Results indicated that greater aerobic fitness was related to greater post-error accuracy and larger Ne/ERN amplitudes in the mostly congruent condition. These findings suggest that higher-fit children might be able to transiently upregulate cognitive control by recruiting reactive control in the mostly congruent condition. Further, greater fitness was related to greater modulation of Ne/ERN amplitude between conditions, suggesting that higher-fit children engaged in more proactive control in the mostly incongruent condition. This study supports the hypothesis that greater childhood fitness is associated with a more flexible shift between reactive and proactive modes of cognitive control to adapt to varying task demands.     

Thyroxine binding to human serum albumin immobilized on sepharose and effects of nonprotein albumin-binding plasma constituents

¹²⁵I-thyroxine (¹²⁵I-T₄) binding to human serum albumin (HSA) covalently attached onto CNBr-activated Sepharose (HSA-Sepharose) was studied.¹²⁵I-T₄ binding to HSA-Sepharose was rapid and saturable. Nonlinear curve-fitting analysis of binding isotherms revealed two classes of binding sites. The values of dissociation constants of high and low affinity sites were 2.19±0.53×10^–6 M and 2.69±0.78×10^–5 M, respectively. The number of binding sites of the high and the low affinity sites were 1.28±0.46 mol/mol and 23.5±9.7 mol/mol of HSA, respectively. Fatty acids and bilirubin competitively inhibited the high-affinity binding of¹²⁵I-T₄ to HSA-Sepharose without affecting the low-affinity binding. 8-anilino-1-naphthalene sulfonic acid (ANS) inhibited the high affinity T₄ binding via reduction of the binding capacity. Unlabeled T₄ showed little inhibition of ANS binding to HSA, as measured by fluorescence intensity. These results suggest that ANS allosterically inhibits the high-affinity T₄ binding to HSA-Sepharose.     

Non-visual effects of the color temperature of fluorescent lamps on physiological aspects in humans

The non-visual effects of the color temperature of fluorescent lamps were reviewed based mainly on our recent studies with special reference to physiological aspects in humans such as arousal level, autonomic nerve system including heart rate variability, blood pressure and body temperature regulation, and sleep architecture. It was concluded that there obviously existed the non-visual effects of the spectral composition of fluorescent lamps on physiological aspects, as predicted based on the functions of the nuclei located on the photic non-visual pathway.     

Molecular characterization of the protease from Clostridium botulinum serotype C responsible for nicking in botulinum neurotoxin complex

A protease was purified from the culture medium of Clostridium botulinum serotype C strain Stockholm (C-St). The purified protease belonged to the cysteine protease family based on assays for enzyme inhibitors, activators and kinetic parameters. The protease formed a binary complex consisting of 41- and 17-kDa proteins held together non-covalently. The DNA sequence encoding the protease gene was shown to be a single open reading frame of 1593 nucleotides, predicting 530 amino acid residues including a signal peptide. The N-terminal region of the native enzyme underwent further proteolytic modification after processing by a signal peptidase. The protease introduced intermolecular cleavage into an intact single chain botulinum neurotoxin (BoNT) at a specific site. Homology modeling and docking simulation of C-St BoNT and C-St protease demonstrated that the specific nicking-site of the BoNT appears to fit into the deep pocket in the active site of the protease.     

Fluid flow and convective transport of solutes within the intervertebral disc

Previous experimental and analytical studies of solute transport in the intervertebral disc have demonstrated that for small molecules diffusive transport alone fulfils the nutritional needs of disc cells. It has been often suggested that fluid flow into and within the disc may enhance the transport of larger molecules. The goal of the study was to predict the influence of load-induced interstitial fluid flow on mass transport in the intervertebral disc.An iterative procedure was used to predict the convective transport of physiologically relevant molecules within the disc. An axisymmetric, poroelastic finite-element structural model of the disc was developed. The diurnal loading was divided into discrete time steps. At each time step, the fluid flow within the disc due to compression or swelling was calculated. A sequentially coupled diffusion/convection model was then employed to calculate solute transport, with a constant concentration of solute being provided at the vascularised endplates and outer annulus. Loading was simulated for a complete diurnal cycle, and the relative convective and diffusive transport was compared for solutes with molecular weights ranging from 400 Da to 40 kDa.Consistent with previous studies, fluid flow did not enhance the transport of low-weight solutes. During swelling, interstitial fluid flow increased the unidirectional penetration of large solutes by approximately 100%. Due to the bi-directional temporal nature of disc loading, however, the net effect of convective transport over a full diurnal cycle was more limited (30% increase). Further study is required to determine the significance of large solutes and the timing of their delivery for disc physiology.     

Deer herbivory affects the functional diversity of forest floor plants via changes in competition-mediated assembly rules

Distorted plant diversity patterns due to ungulate herbivory could be explained by changes in community assembly processes, but the effects of ungulate herbivory on plant community assembly remain unclear. Here, we examined the role of deer herbivory in the regulation of the assembly processes of a forest floor plant community by assessing species and functional diversity in over- and no-grazing plots (control and exclosure plots, respectively) in Shiretoko National Park in Japan. Compared with the exclosure plot, vegetation coverage was considerably lower, and species richness and diversity were higher in the control plot. Functional traits associated with competitive ability (leaf area and chlorophyll content) were significantly higher in the exclosure plot. The pattern of functional diversity changed from overdispersion to clustering with an increase in local crowdedness. This trait clustering indicates that the local communities that were free from ungulate disturbance gradually became dominated by some competitively superior plant species, which led to low species diversity and biotic homogenization. In contrast, the reduction in vegetation due to overgrazing by deer resulted in an increase in the relative importance of stochastic assembly processes, which enabled the coexistence of various species, including less competitive ones. Our results emphasize that although deer overabundance is of concern, their complete exclusion has a negative consequence from an ecological perspective. Because deer herbivory is an inherent process that affects the biodiversity of plants on the forest floor, the establishment of fences requires careful consideration to ensure the conservation of ecological processes and their associated biodiversity.