Distinct forebrain and cerebellar isozymes of type II Ca^(2+)/calmodulin-dependent protein kinase associate differently with the postsynaptic density fraction

Forebrain and cerebellar Type II Ca2+/calmodulin-dependent protein kinases have different subunit compositions. The forebrain holoenzyme, characterized in our laboratory, is a 650-kDa holoenzyme composed of 50-kDa alpha-subunits and 60-kDa beta-subunits assembled in approximately a 3:1 ratio (Bennett, M. K., Erondu, N. E., and Kennedy, M. B. (1983) J. Biol. Chem. 258, 12735-12744). The cerebellar isozyme is a 500-kDa holoenzyme composed of alpha-subunits and beta-subunits assembled in almost the converse ratio, approximately four beta-subunits for each alpha-subunit. When compared by tryptic peptide mapping and by immunochemical techniques, the beta-subunits from the two brain regions are indistinguishable and the alpha-subunits appear closely related. The specific activities, substrate specificities, and catalytic constants of the cerebellar and forebrain isozymes are similar, suggesting that the alpha- and beta-subunits contain similar catalytic sites. However, two differences in the properties of the isozymes may result in functional differences between them in vivo. First, the apparent affinity of the cerebellar kinase for Ca2+/calmodulin is 2-fold higher than that of the forebrain kinase. Second, the two isozymes appear to associate differently with subcellular structures. Approximately 85% of the cerebellar kinase and 50% of the forebrain kinase remain in the particulate fraction after homogenization under standard conditions. However, they are present in different amounts in postsynaptic density fractions. Postsynaptic densities prepared from forebrain contain the forebrain isozyme. Immunochemical measurements show that it comprises approximately 16% of their total protein. In contrast, postsynaptic densities prepared from cerebellum contain the cerebellar isozyme, but it comprises only approximately 1-2% of their total protein. Thus, the alpha-subunit may play a role in anchoring Type II Ca2+/calmodulin-dependent protein kinase to postsynaptic densities

Activation of type II calcium/calmodulin-dependent protein kinase by Ca^(2+)/calmodulin is inhibited by autophosphorylation of threonine within the calmodulin-binding domain

It is now well established that autophosphorylation of a threonine residue located next to each calmodulin-binding domain in the subunits of type II Ca^(2+)/calmodulin-dependent protein kinase causes the kinase to remain active, although at a reduced rate, after Ca^(2+) is removed from the reaction. This autophosphorylated form of the kinase is still sensitive to Ca2+/calmodulin, which is required for a maximum catalytic rate. After removal of Ca^(2+), new sites are autophosphorylated by the partially active kinase. Autophosphorylation of these sites abolishes sensitivity of the kinase to Ca^(2+)/calmodulin (Hashimoto, Y., Schworer, C. M., Colbran, R. J., and Soderling, T. R. (1987) J. Biol. Chem. 262, 8051-8055). We have identified two pairs of homologous residues, Thr^(305) and Ser^(314) in the alpha subunit and Thr^(306) and Ser^(315) in the beta subunit, that are autophosphorylated only after removal of Ca^(2+) from an autophosphorylation reaction. The sites were identified by direct sequencing of labeled tryptic phosphopeptides isolated by reverse-phase high pressure liquid chromatography. Thr^(305-306) is rapidly dephosphorylated by purified protein phosphatases 1 and 2A, whereas Ser^(314-315) is resistant to dephosphorylation. We have shown by selective dephosphorylation that the presence of phosphate on Thr^(305-306) blocks sensitivity of the kinase to Ca^(2+)/calmodulin. In contrast, the presence of phosphate on Ser^(314-315) is associated with an increase in the Kact for Ca^(2+)/calmodulin of only about 2-fold, producing a relatively small decrease in sensitivity to Ca^(2+)/calmodulin

In Defense of the Land Residual Theory and the Absence of a Business Value Component for Retail Property

The temptation is strong for arguing that property values can be broken down into land, improvements, and business value, as only land and improvements are subject to property tax. As sympathetic as the authors are to this motivation, the notion of a long-run business value component for retail property is refuted and the land residual value theory reasserted, while at the same time admitting the possibility of first owner entrepreneurial or development-based value creation. It is argued that any excess property productivity will eventually become attached to the land, and last that option values are an important aspect of land values that would be affected when suggesting that the appropriate value of a given property is the cost of substituting adjacent property.

Eisenstein series for higher-rank groups and string theory amplitudes

Scattering amplitudes of superstring theory are strongly constrained by the requirement that they be invariant under dualities generated by discrete subgroups, E_n(Z), of simply-laced Lie groups in the E_n series (n<= 8). In particular, expanding the four-supergraviton amplitude at low energy gives a series of higher derivative corrections to Einstein's theory, with coefficients that are automorphic functions with a rich dependence on the moduli. Boundary conditions supplied by string and supergravity perturbation theory, together with a chain of relations between successive groups in the E_n series, constrain the constant terms of these coefficients in three distinct parabolic subgroups. Using this information we are able to determine the expressions for the first two higher derivative interactions (which are BPS-protected) in terms of specific Eisenstein series. Further, we determine key features of the coefficient of the third term in the low energy expansion of the four-supergraviton amplitude (which is also BPS-protected) in the E_8 case. This is an automorphic function that satisfies an inhomogeneous Laplace equation and has constant terms in certain parabolic subgroups that contain information about all the preceding terms.Comment: Latex. 38 pages. 1 figure. v2: minor changes and clarifications. v3: minor corrections, version to appear in Communications in Number Theory and Physics. v4: corrections to table

Characterization of IM7/8552 Thin-Ply and Hybrid Thin-Ply Composites

Composite materials have increasingly been used for aerospace applications due to improved performance and reduced weight compared to their metallic counterparts. Inclusion of thin-ply material, plies with cured thickness half or less than standard composites, have potential to improve performance and reduce structural weight. Limited characterization of thin-ply IM7/8552 material in 30 and 70 grams per square meter fiber areal weights has been carried out using a series of selected American Society for Testing and Materials (ASTM) tests. Tests included unnotched tension, unnotched compression, v-notched rail shear, open-hole tension, and open-hole compression. Unidirectional, cross-ply, quasiisotropic and hybrid hard laminates were included in the study, and were compared to standard-ply laminates. Properties compared include fiber volume, laminate moduli, and failure strength, with failure modes also being examined. The thin-ply specimens exhibited similar or superior performance to standard ply laminates in many of the cases compared. Improvements in strength for laminates containing thin-ply material were seen for unidirectional laminates under unnotched tension, quasi-isotropic laminates under unnotched tension and compression, and hard laminates under open hole tension. Additional investigation is required to determine appropriate ply stacking rules for hybrids of thin and standard plies to avoid undesirable failure modes such as axial splitting. However, the observed performance improvements demonstrated by the conducted ASTM tests of hybrid thin-ply hard laminates could have benefits for improved structural weight in aircraft

Demographic Studies on Hawaii's Endangered Tree Snails: Partulina proxima

Populations of the tree snail Partulina proxima, endemic to higher elevations of Molokai, Hawaiian Islands, were studied for 3 years. Analyses of the data derived from 17bimonthly mark-recapture events determined that each tree harbors a small, mostly nonmigratory population of 8-26 snails of which 2-4 are adults; the snails average 4.2 mm long at birth and 21.3 mm long when growth stops; growth is slow, with maturity reached in 5-7 years; annual fecundity averages 6.2 offspring per adult; and mortality is about 98% over the first 4 years of life. Given the high rate of juvenile mortality, adult snails must reproduce for at least 12 years to replace themselves. From this we calculate a minimum maximal life-span of 18-19 years. We conclude that the current high rate of unexplained juvenile mortality, combined with lat e age at first reproduction and low fecundity, place this species at very high risk to any sort of perturbation, particularly any selective predation on adults

A Theory of Mind investigation into the appreciation of visual jokes in schizophrenia

BACKGROUND: There is evidence that groups of people with schizophrenia have deficits in Theory of Mind (ToM) capabilities. Previous studies have found these to be linked to psychotic symptoms (or psychotic symptom severity) particularly the presence of delusions and hallucinations. METHODS: A visual joke ToM paradigm was employed where subjects were asked to describe two types of cartoon images, those of a purely Physical nature and those requiring inferences of mental states for interpretation, and to grade them for humour and difficulty. Twenty individuals with a DSM-lV diagnosis of schizophrenia and 20 healthy matched controls were studied. Severity of current psychopathology was measured using the Krawiecka standardized scale of psychotic symptoms. IQ was estimated using the Ammons and Ammons quick test. RESULTS: Individuals with schizophrenia performed significantly worse than controls in both conditions, this difference being most marked in the ToM condition. No relationship was found for poor ToM performance and psychotic positive symptomatology, specifically delusions and hallucinations. CONCLUSION: There was evidence for a compromised ToM capability in the schizophrenia group on this visual joke task. In this instance this could not be linked to particular symptomatology

Androsterone glucuronide to dehydroepiandrosterone sulphate ratio is discriminatory for obese Caucasian women with polycystic ovary syndrome

BACKGROUND: Androsterone glucuronide (ADTG) concentrations have been suggested as a marker of the effects of androgens at the target tissue level. As the mechanism for hyperandrogenemia in obese and nonobese polycystic ovary syndrome (PCOS) may differ, this study compared the different androgen parameters in non-obese compared to obese women with PCOS, and in normal subjects. METHODS: Eleven non-obese and 14 obese women with PCOS were recruited and compared to 11 control women without PCOS. Total testosterone, dehydroepiandrosterone sulphate (DHEAS), ADTG, and androstenedione were analysed using gold standard tandem mass spectrometry, and the free androgen index (FAI) was calculated. RESULTS: Total testosterone, ADTG and androstendione levels did not differ between non-obese (body mass index (BMI) ≤25 kg/m2) and obese PCOS (BMI >25 kg/m2) but all were significantly higher than for controls (p &lt; 0.01). The ADTG to DHEAS ratio was significantly elevated 39 ± 6 (p &lt; 0.01) in obese PCOS in comparison to non-obese PCOS and controls (28 ± 5 and 29 ± 4, respectively). The free androgen index (FAI) and insulin resistance (HOMA-IR) were significantly higher in obese PCOS compared to non-obese PCOS and controls (p &lt; 0.01). DHEAS was significantly higher in the non-obese versus obese PCOS (p &lt; 0.01). All androgen parameters were significantly lower and sex hormone binding globulin (SHBG) significantly higher in normal subjects compared to those with obese and non-obese PCOS. CONCLUSIONS: The ADTG:DHEAS ratio was significantly elevated in obese PCOS compared to non-obese PCOS and controls suggesting that this may be a novel biomarker discriminatory for obese PCOS subjects, perhaps being driven by higher hepatic 5α reductase activity increasing ADTG formation in these women

The frequency of epstein-barr virus infection and associated lymphoproliferative syndrome after transplantation and its manifestations in children

Twenty cases of Epstein-Barr virus (EBV)-associated lymphoproliferative syndrome (LPS), defined by the presence of EBV nuclear antigen and/or EBV DNA in tissues, were diagnosed in 1467 transplant recipients in Pittsburgh from 1981—1985. The frequency of occurrence in pediatric transplant recipients was 4% (10/ 253), while in adults it was 0.8% (10/1214) (P < .0005). The frequency of LPS in adults declined after 1983 coincidental with the introduction of cyclosporine monitoring. However there was no apparent decline of LPS in children. We describe these ten pediatric cases and one additional case of LPS in a child who received her transplant before 1981. The frequency of EBV infection in 92 pediatric liver recipients was 63%. Of these subjects, 49% were sero-negative and 77% of those acquired primary infection. Of 11 cases of pediatric EBV-associated LPS, 10 were in children who had primary infection shortly before or after transplantation. These results reinforce the impor-tance of primary EBV infection in producing LPS, which was previously shown in adults. Children are at greater risk because they are more likely to be seronegative for EBV and to acquire primary infection. Three clinical types of LPS were recognized in children. The first (5 cases) was a self-limited mononucleo-sislike syndrome. The second syndrome (4 cases) began similarly, but then progressed over the next two months to widespread lymphoproliferation in internal organs and death. The third type (2 cases) was an extranodal intestinal monoclonal B cell lymphoma, occurring late after primary infection. © 1988 by The Williams and Wilkins Co

Unnatural selection in Galapagos : the role of disease in Darwin’s Finches (Geospizinae)

Micro-evolutionary studies, such as those of Darwin’s finches (Geospizinae), have been used as indicators of rates of evolution under natural selection. Today however, such studies may be compromised by unnatural selection. Recently introduced infectious and parasitic agents in Galapagos may hamper our ability to monitor natural evolutionary change in endemic birds, by modifying such change. The opportunity to study natural selection in its iconic site may thus be lost, due to these and other forms of human environmental alteration, which may be replacing non-anthropogenic factors as the principal driver of evolution. To ensure that natural selection continues to shape the biota of Galapagos, anthropogenic impacts including introduced diseases must be managed effectively