Evolution of eutherian cytochrome c oxidase subunit II: heterogeneous rates of protein evolution and altered interaction with cytochrome c

Cytochrome c oxidase subunit II (COII), encoded by the mitochondrial genome, exhibits one of the most heterogeneous rates of amino acid replacement among placental mammals. Moreover, it has been demonstrated that cytochrome c oxidase has undergone a structural change in higher primates which has altered its physical interaction with cytochrome c. We collected a large data set of COII sequences from several orders of mammals with emphasis on primates, rodents, and artiodactyls. Using phylogenetic hypotheses based on data independent of the COII gene, we demonstrated that an increased number of amino acid replacements are concentrated among higher primates. Incorporating approximate divergence dates derived from the fossil record, we find that most of the change occurred independently along the New World monkey lineage and in a rapid burst before apes and Old World monkeys diverged. There is some evidence that Old World monkeys have undergone a faster rate of nonsynonymous substitution than have apes. Rates of substitution at four-fold degenerate sites in primates are relatively homogeneous, indicating that the rate heterogeneity is restricted to nondegenerate sites. Excluding the rate acceleration mentioned above, primates, rodents, and artiodactyls have remarkably similar nonsynonymous replacement rates. A different pattern is observed for transversions at four-fold degenerate sites, for which rodents exhibit a higher rate of replacement than do primates and artiodactyls. Finally, we hypothesize specific amino acid replacements which may account for much of the structural difference in cytochrome c oxidase between higher primates and other mammals.      

Relationships among msx gene structure and function in zebrafish and other vertebrates

The zebrafish genome contains at least five msx homeobox genes, msxA, msxB, msxC, msxD, and the newly isolated msxE. Although these genes share structural features common to all Msx genes, phylogenetic analyses of protein sequences indicate that the msx genes from zebrafish are not orthologous to the Msx1 and Msx2 genes of mammals, birds, and amphibians. The zebrafish msxB and msxC are more closely related to each other and to the mouse Msx3. Similarly, although the combinatorial expression of the zebrafish msx genes in the embryonic dorsal neuroectoderm, visceral arches, fins, and sensory organs suggests functional similarities with the Msx genes of other vertebrates, differences in the expression patterns preclude precise assignment of orthological relationships. Distinct duplication events may have given rise to the msx genes of modern fish and other vertebrate lineages whereas many aspects of msx gene functions during embryonic development have been preserved.      

Canadian-trained Physicians in United States Internships and Residencies: “Operation Retrieval” and Report of Statistics, 1966-1968

In response to a shortage of medical teachers and scientists, A.C.M.C. began “Operation Retrieval” in 1967 in an effort to contact and to survey graduates of Canadian medical schools who are interns and residents in the United States. This paper describes the publications produced for these graduates, and the concerns of graduates as discovered by on-site visits to Los Angeles, Boston and New York. These concerns centre around difficulties in communication with Canada. This paper also gives a statistical report on the numbers of graduates who are interns and residents in the United States, and the locations, fields of specialization and years of graduation of residents. The decreasing numbers are believed to reflect improving Canadian facilities as well as difficulties associated with the American military draft.     

Surface structure changes of rat adipocytes during lypolysis stimulated by various lypolysis stimulated by various lypolytic agents

A qualitative and quantitative electron microscopic study was performed on rat adipocytes during stimulation of lipolysis by various agents. Scanning electron microscopy of control cells revealed a spherical cell with a textured glycocalyx surface exhibiting small irregular projections. Globular surface evaginations or protrusions measuring 8-18 μM in diameter were seen on cell hemispheres, and there was an average of one protrusion for every two hemispheres examined. Distribution analysis showed that 60 percent of the hemispheres had no protrusions, and 25, 10, and 5 percent of the hemispheres had one, two or three protrusions, respectively. Thin-section and freeze- fracture electron microscopy of the protrusions showed a small triglyceride droplet surrounded by a thin cytoplasmic rim that was continuous with the main cytoplasmic matrix. The glycocalyx coating and plasma membrane extended from the cell surface onto, and over, the protrusion. Scanning microscopy of cells stimulated by lipolytic agents, including epinephrine, adrenocorticotropic hormone, theophylline, and dibutyryl cyclic AMP, revealed a dose-dependent increase in the number of protrusions per cell hemisphere. Maximal concentrations of lipolytic hormones cuase an average 2.5-fold increase in the number of protrusions per hemisphere without changing the average size of the protrusions. Only 40 percent of the stimulated cell hemispheres exhibited no protrusions; over 15 percent of the cells contained three or more; and a number of the protrusions were multilobulate. Insulin prevented the increase in the number of protrusions and the change in distribution caused by the lipolytic hormones but did not prevent the increase caused by theophylline and dibutryl cyclic AMP. The data suggest that the protrusions are a structural feature of the cell and may be related to the lypolytic pathway. These observations may help explain some of the discrepant biochemical data relating to hormonal stimulation of lipolysis.     

A Cost-Benefit Analysis of Leaves of Eight Australian Savanna Tree Species of Differing Leaf Life-Span

Cost-benefit analysis of foliar construction and maintenance costs and of carbon assimilation of leaves of differing life-span were conducted using two evergreen, three semi-deciduous, and three deciduous tree species of savannas of north Australia. Rates of radiant-energy-saturated CO₂ assimilation (P _max) and dark respiration were measured and leaves were analysed for total nitrogen, fat, and ash concentrations, and for heat of combustion. Specific leaf area, and leaf N and ash contents were significantly lower in longer-lived leaves (evergreen) than shorter-lived leaves (deciduous) species. Leaves of evergreen species also had significantly higher heat of combustion and lower crude fat content than leaves of deciduous species. On a leaf area basis, P _max was highest in leaves of evergreen species, but on a leaf dry mass basis it was highest in leaves of deciduous species. P _max and total Kieldahl N content were linearly correlated across all eight species, and foliar N content was higher in leaves of deciduous than evergreen species. Leaf construction cost was significantly higher and maintenance costs were lower for leaves of evergreen than deciduous species. Maintenance and construction costs were linearly related to each other across all species. Leaves of evergreen species had a higher cost-benefit ratio compared to leaves of deciduous species but with longer lived leaves, the payback interval was longer in evergreen than deciduous species. These results support the hypotheses that longer lived leaves are more expensive to construct than short-lived leaves, and that a higher investment of N into short-lived leaves occurs which supports a higher P _max over a shorter payback interval.     

Cdk5 is a key factor in tau aggregation and tangle formation in vivo

Tau aggregation is a common feature of neurodegenerative diseases such as Alzheimer's disease, and hyperphosphorylation of tau has been implicated as a fundamental pathogenic mechanism in this process. To examine the impact of cdk5 in tau aggregation and tangle formation, we crossed transgenic mice overexpressing the cdk5 activator p25, with transgenic mice overexpressing mutant (P301L) human tau. Tau was hyperphosphorylated at several sites in the double transgenics, and there was a highly significant accumulation of aggregated tau in brainstem and cortex. This was accompanied by increased numbers of silver-stained neurofibrillary tangles (NFTs). Insoluble tau was also associated with active GSK. Thus, cdk5 can initiate a major impact on tau pathology progression that probably involves several kinases. Kinase inhibitors may thus be beneficial therapeutically.