ATF6ß Deficiency Elicits Anxiety-like Behavior and Hyperactivity Under Stress Conditions.

Activating transcription factor 6 (ATF6) is an endoplasmic reticulum (ER) stress-regulated transcription factor that induces expression of major molecular chaperones in the ER. We recently reported that ATF6ß, a subtype of ATF6, promoted survival of hippocampal neurons exposed to ER stress and excitotoxicity, at least in part by inducing expression of calreticulin, an ER molecular chaperone with high Ca2+-binding capacity. In the present study, we demonstrate that ATF6ß deficiency in mice also decreases calreticulin expression and increases expression of glucose-regulated protein 78, another ER molecular chaperone, in emotional brain regions such as the prefrontal cortex (PFC), hypothalamus, hippocampus, and amygdala. Comprehensive behavioral analyses revealed that Atf6b-/- mice exhibit anxiety-like behavior in the light/dark transition test and hyperactivity in the forced swim test. Consistent with these results, PFC and hypothalamic corticotropin-releasing hormone (CRH) expression was increased in Atf6b-/- mice, as was circulating corticosterone. Moreover, CRH receptor 1 antagonism alleviated anxiety-like behavior in Atf6b-/- mice. These findings suggest that ATF6ß deficiency produces anxiety-like behavior and hyperactivity via a CRH receptor 1-dependent mechanism. ATF6ß could play a role in psychiatric conditions in the emotional centers of the brain.

Cognitive Improvement by Photic Stimulation in a Mouse Model of Alzheimer's Disease.

We previously reported that activity of the large conductance calcium-activated potassium (big-K, BK) channel is suppressed by intracellular Aß in cortical pyramidal cells, and that this suppression was reversed by expression of the scaffold protein Homer1a in 3xTg Alzheimer's disease model mice. Homer1a is known to be expressed by physiological photic stimulation (PS) as well. The possibility thus arises that PS also reverses Aß-induced suppression of BK channels, and thereby improves cognition in 3xTg mice. This possibility was tested here. Chronic application of 6-hour-long PS (frequency, 2 Hz; duty cycle, about 1/10; luminance, 300 lx) daily for 4 weeks improved contextual and tone-dependent fear memory in 3xTg mice and, to a lesser extent, Morris water maze performance as well. Hippocampal long-term potentiation was also enhanced after PS. BK channel activity in cingulate cortex pyramidal cells and lateral amygdalar principal cells, suppressed in 3xTg mice, were facilitated. In parallel, neuronal excitability, elevated in 3xTg mice, was recovered to the control level. Gene expression of BK channel, as well as that of the scaffold protein Homer1a, was found decreased in 3xTg mice and reversed by PS. It is known that Homer1a is an activity-dependently inducible immediate early gene product. Consistently, our previous findings showed that Homer1a induced by electrical stimulation facilitated BK channels. By using Homer1a knockouts, we showed that the present PS-induced BK channel facilitation is mediated by Homer1a expression. We thus propose that PS might be potentially useful as a non-invasive therapeutic measure against Alzheimer's disease.

Antibacterial and antifungal activities of new acylated derivatives of epigallocatechin gallate.

(-)-Epigallocatechin-3-O-gallate (EGCG) has useful antiviral, antimicrobial, antitoxin, and antitumor properties. Previously, Mori et al. (2008) found that addition of long acyl chains (C16-18) to EGCG enhanced its anti-influenza virus activity up to 44-fold. The chemical stability of EGCG against oxidative degradation was also enhanced by acylation. We further evaluated the in vitro activity spectrum of the EGCG derivatives against a wide range of bacteria and fungi. A series of EGCG O-acyl derivatives were synthesized by lipase-catalyzed transesterification. These derivatives exhibited several-fold higher activities than EGCG, particularly against Gram-positive organisms. Antifungal MICs of the derivatives were also two to fourfold lower than those of EGCG. The activities of the EGCG derivatives against Gram-negative bacteria were not distinguishable from those of EGCG. Among the derivatives evaluated, MICs of dioctanoate and palmitate (C16) for 17 Staphylococcus aureus strains were 4-32 µg/ml, although MIC of EGCG for these 17 strains was ≥128 µg/ml. C16 demonstrated rapid bactericidal activity against methicillin-resistant S. aureus (MRSA) ATCC43300 at ≥16 µg/ml. The enhanced activity of C16 against S. aureus was supported by its increased membrane-permeabilizing activity determined by increased SYTOX Green uptake. The EGCG derivatives were exported in Escherichia coli using the efflux pump AcrAB-TolC. The tolC deletion mutant exhibited higher sensitivity to EGCG and the derivatives than wild-type. Addition of long alkyl chains to EGCG significantly enhanced its activities against several bacteria and fungi, particularly against S. aureus including MRSA. C16 might potentially become under specified circumstances an alternative or supplement to antibiotics and disinfectants in the future.

Influences of audio-visual environments on feelings of deliciousness during having sweet foods: an electroencephalogram frequency analysis study.

Feelings of deliciousness during having foods are mainly produced by perceptions of sensory information extracted from foods themselves, such as taste and olfaction. However, environmental factors might modify the feeling of deliciousness. In the present study, we investigated how the condition of audio-visual environments affects the feeling of deliciousness during having sweet foods. Electroencephalograms (EEGs) were recorded from the frontal region of the scalp of healthy participants under virtual scenes of tearoom and construction work, respectively. The participants were asked to rate deliciousness after the recordings. Frequency analyses were performed from the EEGs. During having the foods, occupancy rates of beta frequency band between tearoom scenes and construction work scenes were markedly different, but not in other frequency bands. During having no food, in contrast, there was no difference of occupancy rates in respective frequency bands between the two different scenes. With regard to deliciousness during having sweet foods, all participants rated high scores under the scenes of tearoom than those under the scenes of construction work. Interestingly, there is a positive correlation between occupancy rates of beta frequency band and scores of deliciousness. These findings suggest that comfortable audio-visual environments play an important role in increasing the feeling of deliciousness during having sweet foods, in which beta frequency rhythms may be concerned with producing comprehensive feelings of deliciousness.

Identification and functional analysis of brassicicene C biosynthetic gene cluster in Alternaria brassicicola.

The biosynthetic gene cluster of brassicicene C was identified in Alternaria brassicicola strain ATCC 96836 from genome database search. In vivo and in vitro study clearly revealed the function of Orf8 and Orf6 as a fusicoccadiene synthase and methyltransferase, respectively. The understanding toward the biosynthetic pathway promises construction of this type of diterpene compounds with genetic engineering.

Wax ester production by bacteria.

The enzymological and genetic aspects of microbial metabolism of hydrocarbons have been extensively revealed. Such molecular information is useful for understanding the bioremediation of oil spill environments and production of hydrocarbon-specific fine chemicals.

Pyrogenicity of human adenoviruses.

High doses (>1.56x10(7) p.f.u.) of purified preparations of human adenovirus types 3, 5 and 8 exhibited definite pyrogenic activity when injected intravenously into rabbits. Complete pyrogenic tolerance was obtained not only with homologous types but also with heterologous types of adenovirus. No pyrogenic cross-tolerance was observed between each of these three adenovirus types and paramyxovirus pyrogen or bacterial lipopolysaccharide. Adenovirus pyrogenicity was retained after UV-inactivation, whereas it was inactivated by heating at 56 degrees C for 30 min. Adenovirus pyrogenicity was not neutralized by mixing with homologous type-specific antiserum but non-pyrogenic doses (10(7) p.f.u.) of adenovirus types 3, 5 and 8 became highly pyrogenic in the presence of type-specific antibodies at the optimal virus:antibody ratio. This enhanced pyrogenicity depended upon the virus-antibody complex. From these results, it is probable that the pyrogenic activity of the virus-antibody complex, rather than the pyrogenic activity of the virions, is the main contributor to fever in adenovirus infection under actual physiological conditions.