Formation of False Context Fear Memory Is Regulated by Hypothalamic Corticotropin-Releasing Factor in Mice

Traumatic events frequently produce false fear memories. We investigated the effect of hypothalamic corticotropin-releasing factor (CRF) knockdown (Hy-Crf-KD) or overexpression (Hy-CRF-OE) on contextual fear memory, as fear stress-released CRF and hypothalamic–pituitary–adrenal axis activation affects the memory system. Mice were placed in a chamber with an electric footshock as a conditioning stimulus (CS) in Context A, then exposed to a novel chamber without CS, as Context B, at 3 h (B-3h) or 24 h (B-24h). The freezing response in B-3h was intensified in the experimental mice, compared to control mice not exposed to CS, indicating that a false fear memory was formed at 3 h. The within-group freezing level at B-24h was higher than that at B-3h, indicating that false context fear memory was enhanced at B-24h. The difference in freezing levels between B-3h and B-24h in Hy-Crf-KD mice was larger than that of controls. In Hy-CRF-OE mice, the freezing level at B-3h was higher than that of control and Hy-Crf-KD mice, while the freezing level in B-24h was similar to that in B-3h. Locomotor activity before CS and freezing level during CS were similar among the groups. Therefore, we hypothesized that Hy-Crf-KD potentiates the induction of false context fear memory, while Hy-CRF-OE enhances the onset of false fear memory formation.     

Elevated Expression of CCN3 in Articular Cartilage Induces Osteoarthritis in Hip Joints Irrespective of Age and Weight Bearing

Osteoarthritis (OA) occurs not only in the knee but also in peripheral joints throughout the whole body. Previously, we have shown that the expression of cellular communication network factor 3 (CCN3), a matricellular protein, increases with age in knee articular cartilage, and the misexpression of CCN3 in cartilage induces senescence-associated secretory phenotype (SASP) factors, indicating that CCN3 promotes cartilage senescence. Here, we investigated the correlation between CCN3 expression and OA degenerative changes, principally in human femoral head cartilage. Human femoral heads obtained from patients who received total hip arthroplasty were categorized into OA and femoral neck fracture (normal) groups without significant age differences. Gene expression analysis of RNA obtained from femoral head cartilage revealed that CCN3 and MMP-13 expression in the non-weight-bearing part was significantly higher in the OA group than in the normal group, whereas the weight-bearing OA parts and normal cartilage showed no significant differences in the expression of these genes. The expression of COL10A1, however, was significantly higher in weight-bearing OA parts compared with normal weight-bearing parts, and was also higher in weight-bearing parts compared with non-weight-bearing parts in the OA group. In contrast, OA primary chondrocytes from weight-bearing parts showed higher expression of CCN3, p16, ADAMTS4, and IL-1β than chondrocytes from the corresponding normal group, and higher ADAMTS4 and IL-1β in the non-weight-bearing part compared with the corresponding normal group. Acan expression was significantly lower in the non-weight-bearing group in OA primary chondrocytes than in the corresponding normal chondrocytes. The expression level of CCN3 did not show significant differences between the weight-bearing part and non-weight-bearing part in both OA and normal primary chondrocytes. Immunohistochemical analysis showed accumulated CCN3 and aggrecan neoepitope staining in both the weight-bearing part and non-weight-bearing part in the OA group compared with the normal group. The CCN3 expression level in cartilage had a positive correlation with the Mankin score. X-ray analysis of cartilage-specific CCN3 overexpression mice (Tg) revealed deformation of the femoral and humeral head in the early stage, and immunohistochemical analysis showed accumulated aggrecan neoepitope staining as well as CCN3 staining and the roughening of the joint surface in Tg femoral and humeral heads. Primary chondrocytes from the Tg femoral head showed enhanced expression of Ccn3, Adamts5, p16, Il-6, and Tnfα, and decreased expression of Col2a1 and -an. These findings indicate a correlation between OA degenerative changes and the expression of CCN3, irrespective of age and mechanical loading. Furthermore, the Mankin score indicates that the expression level of Ccn3 correlates with the progression of OA.     

Contact between catalyst and carbon in the tin- and lead- catalyzed gasification of carbon with carbon dioxide

The wettability and distribution of tin and lead metals on a phenol-folmaldehyde resin char were investigated by means of contact angle measurement and microscopic analysis. The wettability on the pelletized char was not so significant. However, stannic oxide was found to be distributed around a tin catalyst particle. This can be considered a result of the vapor phase transport of stannous oxide and its oxidation by CO₂. Stannous oxide was formed through a red-ox type catalysis cycle. On the other hand, in the case of lead-catalyzed gasification, the mobile species was the lead metal itself. Thus, the high catalytic activity of tin and lead metals was appropriately ascribed to an intimate contact between the catalyst and the carbon substrate caused by the vapor phase transportation of stannous oxide and lead metal.     

Ta additive effect on RF magnetron sputtered CoCr films

Magnetic properties for sputtered CoCrTa films (18 at.% Cr and 2.0-3.0 at.% Ta), which were deposited under various background pressures P_i, and argon sputtering pressures, P _Ar, have been examined. The perpendicular anisotropy field H_k for CoCrTa films maintains high values of 5-6 kOe in a wide range of P_i and P_Ar , as compared with that for CoCr films. In order to optimize Ta composition, magnetic properties and crystalline microstructures for Ta additive content (0-4.0 at.%) have been investigated. H_k and perpendicular coercivity H_c⊥ increase with increasing Ta concentration above 2.0 at.% Ta. C-axis orientation is improved by adding Ta to CoCr films. However, above 3.0 at.% Ta, H_c⊥ steeply decreases and domain wall motion is observed, owing to the increase in crystalline grain size. The appropriate Ta composition is 2.0-3.0 at.%     

Effect of aeration and unsaturated fatty acids on expression of the Saccharomyces cerevisiae alcohol acetyltransferase gene

The reduction of acetate ester synthesis by aeration and the addition of unsaturated fatty acids to the medium has been reported to be the result of the reduction in alcohol acetyltransferase (AATase) activity induced by inhibition of this enzyme. However, regulation of the AATase gene ATF1 has not been reported. In this study, ATF1 gene expression was studied by Northern analysis, and the results showed that the ATF1 gene was repressed both by aeration and by unsaturated fatty acids. The results also showed that the reduction of AATase activity is closely related to the degree of repression of ATF1 mRNA, which suggested that the gene repression is the primary means of reducing AATase activity in vivo. Using the Escherichia coli lacZ gene as a reporter gene, it was shown that a 150-bp fragment of the 5' flanking sequence played a major role in the repression by aeration and unsaturated fatty acid addition.     

Gangliosides of dogfish (Squalus acanthias) brain

The major research objectives in organ transplantation are to palliate the lack of organs, to decrease the adverse effects of chronic immunosuppression and to improve medium-term and long-term graft survival. Xenotransplantation and induction of a permanent and specific tolerance to an allograft therefore represent two main lines of research which could partly resolve the problems of organ transplantation. The objective of this article is to evaluate the possible role of gene therapy in the development of xenotransplantation and induction of allograft tolerance. They review the various gene vectors currently available as well as the routes of administration of these vectors specific to transplantation. The place of gene therapy is then evaluated in the context of allo- and xenotransplantation. In allotransplantation, transfection of certain genes of interest into the transplant organ before implantation or into the recipient's immune system is considered. Transfection into the transplant organ of genes coding for immunomodulating cytokines (TGF-beta, IL-4, IL-10, etc.), molecules which block the second signal (CTLA4-Ig) or molecules responsible for apoptosis (Fas/FasL) is discussed. The value of gene therapy in the recipient's immune system consists of transfection onto the recipient's bone marrow cells of genes coding for major histocompatibility system molecules (HLA-DR, DQ, etc.). In xenotransplantation, gene therapy will certainly play a major role in the development of transgenic pigs expressing, on the surface endothelium of their organs, certain human molecules which regulate the activity of complement (CD55, CD59, etc.) or which modify the expression of glycosylated xenoantigens (alpha-galactosyl) recognized by performed antibodies.     

Negative strand of hepatitis C virus RNA in the liver of patients with chronic hepatitis C after interferon treatment

In patients receiving interferon therapy for chronic hepatitis C, serum hepatitis C virus (HCV) RNA often reverts from an undetectable to a detectable form after completion of treatment. Detection of the negative strand of HCV-RNA in liver tissue is regarded as an index of viral proliferation. Therefore, we investigated changes in the hepatic negative-strand HCV-RNA following interferon therapy to determine whether this parameter could predict the long-term response to treatment. The subjects of this study were 27 patients with chronic active hepatitis C. Serum positive-strand and hepatic tissue negative-strand HCV-RNA were detected using polymerase chain reaction. At the completion of interferon treatment, serum HCV-RNA was not detected in 21 patients. One year following treatment it remained undetectable in 14 of these patients but it had reverted to a detectable form in seven. The 14 patients in whom hepatic negative-strand RNA was not detected between 2 weeks and 12 months after treatment, had not relapsed after another year. In the 13 remaining patients, negative-strand RNA was found in liver tissue and serum RNA either reverted to a detectable form or remained detectable throughout. From these findings, we conclude that the detection of negative-strand HCV-RNA in liver tissue 2 weeks after the completion of interferon therapy is useful for predicting the long-term effect of therapy.