Abnormalities in aggression and anxiety in transgenic mice overexpressing activin E

To study the function of activin E, a TGF-β superfamily member, in the regulation of affective behavior, we investigated the behavior of transgenic mice overexpressing activin E (TgActβE mice). Male TgActβE mice showed aggressive behavior in resident-intruder tests. In elevated plus-maze tests, the percentage of open arm entries was significantly increased in female TgActβE mice compared with that in wild-type mice. Furthermore, female TgActβE mice stayed in the central area for a significantly longer time than wild-type mice in open field tests. These results indicated that TgActβE mice had less anxiety-like behavior. The number of restraint-stress-evoked c-Fos-positive cells in the hypothalamic paraventricular nucleus in TgActβE mice was significantly decreased compared with that in wild-type mice. This suggests that synthesis of corticotrophin-releasing hormone induced by stress was decreased in TgActβE mice. Taking these results together, activin E may act as a regulator of the hypothalamic-pituitary-adrenal axis.     

Polo-like kinase 1 is required for localization of Posterior End Mark protein to the centrosome-attracting body and unequal cleavages in ascidian embryos

In ascidian embryos, the posterior-localized maternal factor Posterior End Mark (PEM) is responsible for patterning embryos along the anterior-posterior axis with regard to both cleavage pattern involving unequal cell divisions and gene expression. Although PEM plays important roles in embryogenesis, its mechanism of action is still unclear because PEM has no known functional domain. In the present study, we explored the candidate of PEM partner proteins in Halocynthia roretzi using yeast two-hybrid screening. We isolated a homologue of Polo-like kinase 1 (Plk1), a key regulator of cell division and highly conserved in eukaryotes, as the first potential binding partner of PEM. We biochemically confirmed that interaction occurred between the Plk1 and PEM proteins. Immunostaining showed that Plk1 protein concentrates in the centrosome-attracting body (CAB) at the posterior pole, where PEM protein is also localized. The CAB is a subcellular structure that plays an important role in generating the posterior cleavage pattern. Plk1 localization to the CAB was dependent on the cell cycle phases during unequal cleavage. Inhibition of Plk1 with specific drugs resulted in failure of the nucleus to migrate towards the posterior pole and formation of a microtubule bundle between the CAB and a centrosome, similarly to inhibition of PEM function, suggesting that both proteins are involved in the same process of unequal cleavages. This interrupted nuclear migration was rescued by overexpression of PEM. In Plk1-inhibited embryos, the localization of PEM protein to the CAB was impaired, indicating that Plk1 is required for appropriate localization of PEM.     

Selective evaluation of high density lipoprotein from mouse small intestine by an in situ perfusion technique

The small intestine (SI) is the second-greatest source of HDL in mice. However, the selective evaluation of SI-derived HDL (SI-HDL) has been difficult because even the origin of HDL obtained in vivo from the intestinal lymph duct of anesthetized rodents is doubtful. To shed light on this question, we have developed a novel in situ perfusion technique using surgically isolated mouse SI, with which the possible filtration of plasma HDL into the SI lymph duct can be prevented. With the developed method, we studied the characteristics of and mechanism for the production and regulation of SI-HDL. Nascent HDL particles were detected in SI lymph perfusates in WT mice, but not in ABCA1 KO mice. SI-HDL had a high protein content and was smaller than plasma HDL. SI-HDL was rich in TG and apo AIV compared with HDL in liver perfusates. SI-HDL was increased by high-fat diets and reduced in apo E KO mice. In conclusion, with our in situ perfusion model that enables the selective evaluation of SI-HDL, we demonstrated that ABCA1 plays an important role in intestinal HDL production, and SI-HDL is small, dense, rich in apo AIV, and regulated by nutritional and genetic factors.     

Olfactory Evoked Potential Produced by Electrical Stimulation of the Human Olfactory Mucosa

Most physiological studies of the human olfactory system haveconcentrated on the cortical level; the olfactory bulbar levelhas been studied rarely. We attempted to stimulate the humanolfactory mucosa by electrical pulse to detect the bulbar potentials.Electrical stimulation (2 mA, 0.5 ms) of the human olfactorymucosa evoked a change in potential recorded from the frontalsector of the head. A negative peak of the evoked potentialthat occurred at 19.4 ms (grand means, n = 5) after stimulationwas the clearest. The highest amplitude of the potential wasrecorded from the frontal sector of the head on the stimulatedside. Our findings were similar to the experimental resultsobtained from the olfactory bulbs of animals. This evoked potentialwas considered to be the human olfactory bulbar potential. Whenthe subjects were stimulated by applying electricity to theolfactory mucosa, no sensation of smell occurred even thoughevoked potentials were recorded. Evoked potentials were recordedonly when the stimulating electrode was located in the olfactorycleft. When the stimulating electrode was outside the olfactorycleft, the stimulation caused pain. The trigeminal nerve seemedto be stimulated by electricity. Olfactory evoked potentialsproduced by the electrical stimulation of the human olfactorymucosa should aid the research on human olfactory physiology,and may be applicable to clinical tests of olfactory dysfunction.Chem. Senses 22: 77–81, 1997.     

Impact of long-term continuous positive airway pressure on liver fat in male obstructive sleep apnea patients with fatty liver

Sleep and Biological Rhythms - Obstructive sleep apnea (OSA) is an established factor in the pathogenesis and exacerbation of fatty liver disease. However, randomized controlled trials have failed...     

Alterations in membrane fluidity during keratinocyte differentiation measured by fluorescence polarization

Summary The epidermis shows a distinctive pattern of differentiation wherein keratinocytes proliferate in the basal cell layer and mature into spinous and granular cells. Using a discontinuous density-gradient centrifugation method, guinea-pig keratinocytes were separated into high (HDF), intermediate (IDF), and low (LDF) density fractions. Morphological and flow cytometrical observations demonstrated that HDF, IDF, and LDF were basal, spinous, and granular cell-rich fractions, respectively. Membrane fluidity of the fractionated keratinocytes was measured by diphenylhexatriene fluorescence polarization. Polarization (p)-value of keratinocytes was negatively correlated with temperature. At each temperature, HDF cells showed a lower p-value than IDF or HDF cells except at 40° C. Since a low p-value indicates a high degree of Brownian motion, membrane fluidity is higher in basal cells and lower in spinous and granular cells. Our results indicate that membrane fluidity of guinea-pig keratinocytes decreases during their maturation.