Diurnal rhythms of body temperature, heart rate, and behaviour in the stanchioned adult Shiba goats

Using a data logger system, body temperature (dorsal subcutaneous temperature), heart rate, ingestive or ruminating behaviour and posture in adult Shiba goats tied to a stanchion were recorded automatically during 24 hours, to obtain basic information on the biological rhythms. A 600 g of usual ration mixed with hay cube, hay, beet pulp and wheat bran was fed twice a day (morning; 9:00-9:30, evening; 16:00-16:30). Animals kept under an artificial photoperiod (12L-12D, light period; 5:30-17:30) and about 10 degrees C room temperature. 1) Diurnal patterns of the above-mentioned items were recorded, mutual relationships relationships between these items were revealed. 2) The heart rate was higher after morning feeding, or during a light period and decreased gradually from midnight to early morning. Twice feeding greatly increased the heart rate. 3) The body temperature was lower in the early morning and increased gradually after morning feeding and showed the highest level during 1 to 1.5 hours after evening feeding. After that it decreased gradually till the early morning. 4) The numbers of jaw movement (bites/min) were a 70-90 bites in the ingestive behaviour and a 80-90 bites in the ruminating behaviour at dark period. 5) The total heart rate was a 110000 to 120000 beats/day, the total biting time was a 9.5 hours/day, and the mean standing time was a 9.3 to 11.7 hours/day. The standing time during light period (12 hours) was a 7.3 to 9.9 hours and that during dark period (12 hours) was a 1.8 to 2 hours.     

Ring 18 mosaicism in identical twins

Summary Male identical twins with r(18)/normal mosaicism are reported. Twin 1 has the characteristic manifestations of the r(18) syndrome, but twin 2 shows a normal phenotype. Cytogenetic study of cultured lymphocytes revealed that the proportions of r(18) are 19.7% and 19.2%, respectively. However in the fibroblast cultures, the ring is observed in 51% of cells in twin 1 and in 0% in twin 2. The mechanism of the occurrence of the discrepant phenotypes in the twins is discussed.     

AMPK regulates cell shape of cardiomyocytes by modulating turnover of microtubules through CLIP‐170

AMP‐activated protein kinase (AMPK) is a multifunctional kinase that regulates microtubule (MT) dynamic instability through CLIP‐170 phosphorylation; however, its physiological relevance in vivo remains to be elucidated. In this study, we identified an active form of AMPK localized at the intercalated disks in the heart, a specific cell–cell junction present between cardiomyocytes. A contractile inhibitor, MYK‐461, prevented the localization of AMPK at the intercalated disks, and the effect was reversed by the removal of MYK‐461, suggesting that the localization of AMPK is regulated by mechanical stress. Time‐lapse imaging analysis revealed that the inhibition of CLIP‐170 Ser‐311 phosphorylation by AMPK leads to the accumulation of MTs at the intercalated disks. Interestingly, MYK‐461 increased the individual cell area of cardiomyocytes in CLIP‐170 phosphorylation‐dependent manner. Moreover, heart‐specific CLIP‐170 S311A transgenic mice demonstrated elongation of cardiomyocytes along with accumulated MTs, leading to progressive decline in cardiac contraction. In conclusion, these findings suggest that AMPK regulates the cell shape and aspect ratio of cardiomyocytes by modulating the turnover of MTs through homeostatic phosphorylation of CLIP‐170 at the intercalated disks.     

The Effects of Magnesium Deficiency on Molybdenum Metabolism in Rats

Our previous report indicated that magnesium (Mg) deficiency increased molybdenum (Mo) concentration in the rat liver, suggesting the possibility that Mg deficiency affects Mo metabolism. Growing male rats were given a control diet or a Mg-deficient diet for 4 weeks. Urine and feces were collected during the second and fourth weeks of the feeding trial. The liver, kidney, spleen, skeletal muscle, and blood were collected at the end of the feeding trial. Mg deficiency did not affect the apparent absorption of Mo, but it reduced urinary excretion of Mo. The retention of Mo tended to be higher in the Mg-deficient group than in the control group. Hepatic Mo concentration was higher in the Mg-deficient group than in the control group, but Mg deficiency did not affect Mo concentration in other tissues and plasma. Mg deficiency downregulated the mRNA expression of Mo transporter 2 (MOT2) in the liver, but not in the kidney. These results suggest that Mg deficiency decreases urinary Mo excretion, which is too slight to affect plasma Mo concentration, and that Mg deficiency selectively disturbs the homeostatic mechanism of Mo in the liver, which is not related to the mRNA expression of MOT2 in the liver.     

Studies on Phenolic Lactones

The synergistic action of phenolic lactones on allethrin and pyrethrin were investigated from the mortality of synergized pyrethroids against rice-weevil by petri-dish method.

In the series of α-benzylidene-γ-butyrolactones, (±) hibalactone and α-piperonylidenebutyrolactone were appreciably sy~ergistic on allethrin although less effective than piperonyl butoxide. (±) Hinokinin, 2-piperonylidene-3-piperonyl-l,4-butanediol also showed week activation, but α-benzylidene-, α-anisylidene-, α-veratrylidene-butyrolactone, α-piperonylidenea-α’-piperonyl-tetrahydrofuran, α-trirnethoxybenzylidene-β-trimethoxybenzyl-butyrolactone were not synergistic on the insecticidal action.

In the series of synergized pyrethrin, (±) hibalactone and α-piperonylidene-butyrolactone showed week synergism but the other test compounds showed no appreciable synergism.     

Diterpenoid Total Synthesis

A total synthesis of racemic 4-epipimaric and 4-episandaracopimaric acids is described.     

Tetrahydrobiopterin Biosynthesis Enhanced by Lipopolysaccharide Stimulation in Murine Neuroblastoma Cell Line N1E-115

Abstract: We investigated for the first time the effect of lipopolysaccharide and the signal transduction pathway on the biosynthesis of tetrahydrobiopterin [(6 R - l - erythro -1',2'-dihydroxypropyl)-2-amino-4-hydroxy-5,6,7,8-tetrahydropteridine], the cofactor for the enzymatic hydroxylation of the aromatic amino acids, in the murine neuroblastoma cell line N1E-115, which synthesizes tetrahydrobiopterin constitutively. Activation of N1E-115 cells with 1 µg/ml lipopolysaccharide resulted in statistically significant increases in both intracellular tetrahydrobiopterin contents and the activity ( V _max) of GTP cyclohydrolase I, a rate-limiting enzyme in tetrahydrobiopterin de novo biosynthesis. Following simultaneous addition of the inhibitors of protein tyrosine kinases and GTP-binding proteins into serum-free culture media with lipopolysaccharide, we analyzed the transduction pathway of lipopolysaccharide signal toward the tetrahydrobiopterin biosynthetic system in N1E-115 cells. Our data indicate the following conclusions: (a) Protein tyrosine kinase systems are involved in mediating lipopolysaccharide signal to tetrahydrobiopterin production, and (b) there may be a cross-talk between GTP-binding protein and the protein tyrosine kinase system in mediating lipopolysaccharide signal. These observations suggest that a neuronal cell such as N1E-115, which barely expresses CD14 on its cell surface, responds to lipopolysaccharide like macrophages and monocytes in the absence of soluble CD14.     

Self-renewal of acute lymphocytic leukemia cells is limited by the Hedgehog pathway inhibitors cyclopamine and IPI-926

Conserved embryonic signaling pathways such as Hedgehog (Hh), Wingless and Notch have been implicated in the pathogenesis of several malignancies. Recent data suggests that Hh signaling plays a role in normal B-cell development, and we hypothesized that Hh signaling may be important in precursor B-cell acute lymphocytic leukemia (B-ALL). We found that the expression of Hh pathway components was common in human B-ALL cell lines and clinical samples. Moreover, pathway activity could be modulated by Hh ligand or several pathway inhibitors including cyclopamine and the novel SMOOTHENED (SMO) inhibitor IPI-926. The inhibition of pathway activity primarily impacted highly clonogenic B-ALL cells expressing aldehyde dehydrogenase (ALDH) by limiting their self-renewal potential both in vitro and in vivo. These data demonstrate that Hh pathway activation is common in B-ALL and represents a novel therapeutic target regulating self-renewal and persistence of the malignant clone.