Kinase Activity of PAR1b,Which Mediates Nuclear Translocation of the BRCA1 Tumor Suppressor,Is Potentiated by Nucleic Acid-Mediated PAR1b Multimerization

PAR1b is a cytoplasmic serine/threonine kinase that controls cell polarity and cell–cell interaction by regulating microtubule stability while mediating cytoplasmic-to-nuclear translocation of BRCA1. PAR1b is also a cellular target of the CagA protein of Helicobacter pylori, which leads to chronic infection causatively associated with the development of gastric cancer. The CagA-PAR1b interaction inactivates the kinase activity of PAR1b and thereby dampens PAR1b-mediated BRCA1 phosphorylation, which reduces the level of nuclear BRCA1 and thereby leads to BRCAness and BRCAness-associated genome instability underlying gastric carcinogenesis. While PAR1b can multimerize within the cells, little is known about the mechanism and functional role of PAR1b multimerization. We found in the present study that PAR1b was multimerized in vitro by binding with nucleic acids (both single- and double-stranded DNA/RNA) via the spacer region in a manner independent of nucleic-acid sequences, which markedly potentiated the kinase activity of PAR1b. Consistent with these in vitro observations, cytoplasmic introduction of double-stranded DNA or expression of single-stranded RNA increased the PAR1b kinase activity in the cells. These findings indicate that the cytoplasmic DNA/RNA contribute to nuclear accumulation of BRCA1 by constitutively activating/potentiating cytoplasmic PAR1b kinase activity, which is subverted in gastric epithelial cells upon delivery of H. pylori CagA oncoprotein.     

Muscle Fiber Composition Changes after Selective Nerve Innervation

Facial nerve paralysis interferes with mimetic muscle function. To reconstruct natural facial movement, free muscle flaps are transplanted as new muscles. However, it is difficult to maintain resting tonus. A dual innervation technique in which other nerves such as the hypoglossal nerve or contralateral facial nerve are added is often applied. Using 10-week-old rats (n = 10), the masseteric and hypoglossal nerves were cut, and the distal stump of the masseteric nerve and the proximal stump of the hypoglossal nerve were then sutured (suture group). In the other group, the masseteric nerve was cut and cauterized (cut group). Immunohistochemistry and microarray were performed on the extracted masseter muscle. The immunohistochemistry results suggested that the muscles in the suture group obtained oxidative characteristics. The microarray showed the genes involved in mitochondrial function, including Perm1. In summary, our data support the validity of the dualinnervation technique for facial paralysis treatment.     

Microscopically-viewed relationship between the chain conformation and ultimate Young's modulus of a series of arylate polyesters with long methylene segments

Relationship between the chain conformation in the crystal lattice and the ultimate Young's modulus has been discussed on the basis of the crystal structural information revealed by the X-ray diffraction analysis for a series of arylate polyesters with long methylene segments (–[–COC₆H₄CO–O(CH₂)_mO–]_n–). The X-ray structural analysis revealed that the molecular chains take the all-trans-zigzag conformations for all of the even-numbered polyesters and their model compounds as well as the odd-numbered polyesters with the methylene segmental length longer than (CH₂)₁₄. These chain conformations have been correlated well to the ultimate Young's modulus along the chain axis or the crystallite modulus E_c, which has been estimated experimentally by the X-ray diffraction method under a constant stress and also predicted theoretically using the X-ray-analyzed crystal structures on the basis of the molecular mechanics method. The E_c was found to show the minimum at around m = 4–6 and increased gradually with an increment of m and approached the crystallite modulus of polyethylene, 235 GPa (X-ray value) ∼ 316 GPa (calculate) at an infinite m value. This behavior of E_c as a function of the number of methylene segmental units m was reasonably interpreted by developing the theoretical equation of E_c for a simplified zigzag chain model composed of a repetition of two linear rods representing the benzene–ester and methylene segmental parts respectively. These findings may promise that the mechanical property of arylate polyester can be controlled by adjusting the methylene segmental length m.     

Comparison between Lamarckian and Darwinian Evolution on a Model Using Neural Networks and Genetic Algorithms

In this paper, we study the relationship between learning and evolution in a simple abstract model, where neural networks capable of learning are evolved using genetic algorithms (GAs). Each individual tries to acquire a proper behavior under a given environment through its lifetime learning, and the best individuals are selected to reproduce offspring, which then conduct lifetime learning in the succeeding generation. The connective weights of individuals' neural networks undergo modification, i.e., certain characters will be acquired, through their lifetime learning. By setting various rates for the heritability of acquired characters, which control the strength of ‘Lamarckian’ strategy, we observe adaptational processes of populations over successive generations. By taking the degree of environmental changes into consideration, we show the following results. Under static environments, populations with higher rates of heritability adapt themselves more quickly toward the environments, and thus perform well. On the other hand, under nonstationary environments, populations with lower rates of heritability not only show more stable behavior against environmental changes, but also maintain greater adaptability with respect to such changing environments. Consequently, the population with zero heritability, i.e., the Darwinian population, attains the highest level of adaptation towards dynamic environments. Received February 1999 / Revised September 1999 / Accepted in revised form September 1999     

Evidence for trail-pheromone precursor in termiteReticulitermes speratus (Kolbe) (Rhinotermitidae: Isoptera)

Whole body extracts of the termite,Reticulitermes speratus, were subjected to various chemical operations and bioassays to examine the presence of trail-pheromone precursor. Fractions that mainly contained fatty acid esters were obtained from hexane extracts by means of silica gel column chromatography. Trail-following activity of the fractions was activated by alkaline hydrolysis, while the original fractions did not show any conspicuous activity. Bioassay showed that the activity of hydrolyzed product was approximately 20 times as high as the original hexane extract. This suggests that the precursor candidate could be stored in termite bodies as an esterified form. Chemical analyses revealed that the complete structure of the hydrolyzed product was coincident with that of the native pheromone ((Z,Z,E)-3,6,8-dodecatrien-1-ol).     

Pharmaceutical Characteristic Difference of Several Kinds of Nitroglycerin Tablets

In recent years, Nitroglycerin(NG) has been reevaluated as to its usefulness against angina pectoris. A number of new dosage forms of NG have been developed by pharmaceutical companies. However, there is still a great demand for NG sublingual tablets as a specific medicine to deal with angina pectoris attacks. NG has a high volatility, so patients need to pay attention to the handling and carrying of NG tablets. Recently, new NG tablets have been manufactured by several companies. These NG tablets are designed to either prevent or retard NG volatility from the NG tablet.

Newly designed tablets, Nitrostat(NS), Nitropan(NP) and conventional nitroglycerin tablets (Yamakawa(YK)) were examined to elucidate their pharmaceutical characteristics. The characteristics examined were as follows: measurement of remaining quantity of NG after various storage conditions, hardness test, friability test, content uniformity test and disintegration test. As a result, NP was superior for its ability to prevent NG volatility as compared to NS and YK under all experimental conditions tested. NP also gave excellent results for all analyses.     

Concerns About Professional Schools.

Comments on the article by Peterson (see record 2003-08988-002) and asserts that the professional work of clinical psychologists has many different facets, most of which are not easy to evaluate. Furthermore, it is difficult to generalize about professional schools because, as Peterson pointed out and as research affirms, they differ greatly in student quality and in the quality of their graduates. But it is exactly those differences that require closer scrutiny than they may have received so far. Peterson maintains that the effects of training must ultimately be gauged by the performance of graduates in professional work. We endorse that view and echo the urgency expressed by Peterson in his call to get on with the job. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Measurement of AC dissipation current in oil-film composite insulating system

The electric field dependence of tanδ in oil-film composite insulating system sometimes has a peak and then decreases. This is known as the Garton effect. It is caused by the fact that at high voltages, the contribution of carriers in oil to the conduction loss does not last through an entire alternating field cycle. Since the separation of the loss current from the extremely large capacitive current is usually very difficult, the nonlinear ac dissipation current waveform caused by the Garton effect has not been measured. The authors developed a new method for the measurement of high-field ac dissipation current in polymeric insulating materials. This technique was applied to the detection of nonlinear dissipation current and its waveform in oil-film composite insulating system associated with the Garton effect. We measured the variation of dissipation current with applied field and its frequency.     

Formation of red pigment by a two-step 2-thiobarbituric acid reaction of alka-2,4-dienals. Potential products of lipid oxidation

Reaction of 2,4-hexadienal, 2,4-nonadienal and 2,4-decadienal with 2-thiobarbituric acid (TBA) in aqueous acetic acid produced a 532-nm absorbing red pigment. While the 1∶1 reaction of the aldehyde and TBA produced little pigment, reaction of the aldehyde with an excess amount of TBA produced significant amounts. Instant heating of the reaction mixture did not produce the pigment. However, initial reaction at 5°C and subsequent heating to 100°C produced the pigment efficiently (two-step reaction). Pigment formation required water and dissolved oxygen. The yield of the pigment from the alka-2,4-dienals was 1/10–1/20 of that from malonaldehyde. In the first step of the reaction at 5°C, the 1∶1 adducts of the aldehydes at the5-position of TBA and several other uniden-tified adducts were formed. In the second step, these adducts were converted at 100°C, in the presence of water and oxygen, into the red pigment. The structure of the red pigment from 2,4-hexadienal was elucidated to be the 1∶2 adduct of malonaldehyde and TBA. 2-Hexenal andt-butylhydroperoxide showed marked synergistic effects on the pigment formation from the alka-2,4-dienals. Red pigment formation due to the alka-2,4-dienals may be enhanced by the presence of other aldehydes and hydro-peroxides.