The phylogenetic odyssey of the erythrocyte. II. The early or invertebrate prototypes

Freely existing hemoglobin-bearing cells suspended in a plasmic milieu (erythrocytes) are found in a relatively small number of taxanomically scattered invertebrates. These species include some annelids, echiurids, molluscs, phoronids, nemerteans and echinoderms, e.g. Pista pacifica, Urechis caupo, Noetia ponderosa, Phoronis australis, Lineus fuscoviridis and Cucumaria miniata respectively. The typical invertebrate erythrocyte (hemocyte, coelomocyte) can be described as permanently nucleated, considerably larger than the human red cell, oval or circular in configuration and spherical, biconvex or flattened in profile. The marginal band of the erythrocyte, a bundle of subplasmalemmal microtubules that circumscribes the periphery of the cell and lies in the plane parallel to its flat surface makes its first appearance in certain invertebrates. This structure in association with the cell surface-associated cytoskeleton is responsible for the flattened elliptical shape seen in some invertebrate erythrocytes and endows them with flexibility and resilience to mechanical forces. This in an evolutionarily persistent characteristic that is retained throughout the submammalian vertebrates. The erythrocytes of invertebrates are more morphologically and functionally diversified than the mammalian model. In addition to respiratory activities (oxygen storage and transport) they can sometimes function as vendors of nutrients and participate in other less obvious processes. These cells therefore frequently not only retain organelles that are usually discarded by vertebrate erythrocytes (ribosomes, golgi apparatus, etc.) but may also depending upon the species, manifest in their cytoplasm organelles and inclusions that are not a normal component of developing or mature submammalian vertebrate and mammalian erythroid cells. Examples of the latter are pigment granules, lipid droplets, extensive glycogen stores and prominent Prussian blue positive inclusions. Erythrocytes in the invertebrates, though presenting certain cytologic and functional features in common, are a heterogenous collection of cells, each tailored for a specific species or group of organisms.     

The phylogenetic odyssey of the erythrocyte. III. Fish, the lower vertebrate experience.

The piscine erythrocyte can be considered the prototype of the red cells that are distributed among inframmalian vertebrates. It is a permanently nucleated, hemoglobin-ladened, oval, flattened, biconvex disc. Ultrastructurally it demonstrates a cytoskeleton comprised of a marginal band and a membrane skeleton which are responsible for the erythrocyte's conversion to an ellipsoid during morphogenesis and endow it with resilience to physical trauma. Erythropoiesis initiates in the yolk sac, followed in many fishes, by the intermediate cell mass. These sites are the sources of the transitory, primitive generation red cells which apparently make their first phylogenetic appearance in fishes and which are subsequently represented in all classes of vertebrates including mammals. Production of definitive generation erythrocytes is centered in evolutionary "pre-splenic" tissue of the gastrointestinal tract or in the spleen in cyclostomes, dipnoi, and chondrichthyes while in teleosts it is typically located in the kidneys with or without splenic participation. The blood is a major site of erythrocyte maturation in the lower fishes and exhibits significant numbers of immature erythroid cells plus occasional mitotic figures. Some teleosts also circulate developing erythroid cells. Certain fishes have occasional circulating erythroplastids, conceptually a portent of phylogenetic changes in higher vertebrates. Remarkably, some bristlemouths have denucleated erythrocytes exclusively in the circulation. The largest piscine erythrocytes are found in the dipnoi, myxines, and chondrichthyes. Primitive fish with the exception of the endothermic sharks tend to have lower hemoglobin concentrations than the modern teleosteans. The very highest hemoglobin concentrations are attained by the endothermic scombrids. Erythrocyte-based data have a broad extent and are variably affected by age, sex, season and environment. This report includes a substantial selection of illustrations (fish species and rbc micrographs).     

Integrating the universal metabolism into a phylogenetic analysis

The darwinian concept of "descent with modification" applies to metabolic pathways: pathways sharing similarities must have inherited them from an exclusive, hypothetical ancestral pathway. Comparative anatomy of biochemical pathways is performed using five criteria of homology. Primary homologies of "type I" were defined as several pathways sharing the same enzyme with high specificity for its substrate. Primary homologies of "type II" were defined as the sharing of similar enzymatic functions, cofactors, functional family, or recurrence of a set of reactions. Standard cladistic analysis is used to infer the evolutionary history of metabolic development and the relative ordering of biochemical reactions through time, from a single matrix integrating the whole basic universal metabolism. The cladogram shows that the earliest pathways to emerge are metabolism of amino acids of groups I and II (Asp, Asn, Glu, and Gln). The earliest enzymatic functions are mostly linked to amino acid catabolism: deamination, transamination, and decarboxylation. For some amino acids, catabolism and biosynthesis occur at the same time (Asp, Glu, Lys, and Met). Catabolism precedes anabolism for Asn, Gln, Arg, Trp, His, Tyr, and Phe, and anabolism precedes catabolism for Pro, Ala, Leu, Val, Ile, Cys, Gly, Ser, and Thr. The urea cycle evolves from arginine synthesis. Metabolism of fatty acids and sugars develops after the full development of metabolism of amino acids of groups I and II, and they are associated with the anabolism of amino acids of groups III and IV. Syntheses of aromatic amino acids are branched within sugar metabolism. The Krebs cycle occurs relatively late after the setting of metabolism of amino acids of groups I and II. One portion of the Krebs cycle has a catabolic origin, whereas the other portion has an anabolic origin in pathways of amino acids of groups III and IV. It is not possible to order glycolysis and gluconeogenesis with regard to the Krebs cycle, as they all belong to "period 6." Pentose-phosphate and Calvin cycles are later (periods 7 and 8, respectively). Cladistic analysis of the structure of biochemical pathways makes hypotheses in biochemical evolution explicit and parsimonious.     

The odyssey of k-ras

A mechanism that regulates K-Ras signaling specificity by altering its subcellular location is presented by Bivona et al. (2006). Phosphorylation of its membrane-anchoring domain by PKC drives K-Ras off of the plasma membrane and onto the outer mitochondrial membrane where it induces cell death.     

Post-natal maturation of the retina in the albino rat. I. The pigment epithelium

The Authors studied the postnatal development of the retinal pigment epithelium in the albino rat, in order to elucidate its morphological and functional evolution, correlated to the numerous functional roles played in Vertebrates (Scheme 1). At birth, epithelial cells show few cytoplasmic organules and the apical surface provided of small depressions. From the third to the fifth postnatal day the first apical microfolds surround the depressions. From the seventh to the ninth day inner segments develop, whilst the apical surface of the epithelial cells is covered by many finger-like microfolds. During the eleventh postnatal day the buds of the outer segments and many lamellar microfolds can be demonstrated. During the sixteenth day the retina reaches its adult morphology. It is therefore well-evident that birth, similarly to many other Vertebrates, is not the last step, but only a moment, in the development of the retina: this process is completed only during postnatal life, when environmental light is able to stimulate every ocular structure.     

The odyssey of new production

In studies of primary production of the open ocean, the measurement of new production is often considered a measure of the degree of eutrophication. Because of new research this is questionable, which in our opinion, calls for a refinement to the original concept. We believe that the measure of variable fluorescence is pivotal to a new understanding. Our research enforces the growing conviction that the measurement of Fv/Fm can be interpreted as an analogue for nutrient stress. We measured variable fluorescence in axenic cultures at the CCMP at the Bigelow Laboratory. The Fv/Fm of cultures, upon transfer to new media reached a maximum followed by a decline after approximately 30 days. The rate of decline does not appear to be species specific. Most of the clones remained relatively high after 30 days. The high Fv/Fm values observed in nutrient-replete cultures are not characteristic of the oligotrophic surface waters off Florida and the Bahamas, but are approached in the eutrophic waters of the Gulf of Maine. In contrast, Fv/Fm measurements of attached macroalgae and coral zooxanthellae are characteristically much higher than microalgae of either oligotrophic or eutrophic regions. Accordingly, we advance the case for interpretation of Fv/Fm in terms of nutrient stress in ecological studies and advocate that the old concept of new production should be modified.     

On the removal of air-borne droplets by the human respiratory tract: I. The lung

Calculations as to the fate of air-borne particles in the respiratory tract are given in a paper by W. Findeisen (1935). It is the purpose of the present paper to extend and modify these calculations. The results obtained for total retention in the lungs are found to be in general agreement with published data (cf. Landahl and Herrmann, 1948). The calculated results also give information on the amounts deposited in various regions as well as the amounts retained in different fractions of expired air. The work described in this paper was done in part under contract between the Medical Division, Chemical Corps, U. S. Army, and the University of Chicago Toxicity Laboratory. Under the terms of the contract the Chemical Corps neither restricts nor is responsible for the opinions or conclusions of the author.     

Use of erythrocyte diagnostic agents in the universal system of serological reactions

A method of parallel serologic studies of the material for the detection of specific antigen or antibodies is proposed. This method is not inferior to the known systems of serologic tests (passive hemagglutination-antigen neutralization tests, passive hemagglutination--antibody neutralization tests, etc) in sensitivity and economy, but exceeds all of them in informative value. The method has been tested both experimentally and in the epizootic study of plague infection used as a model. A serologic tests with the use of erythrocyte diagnosticums are based on a universal principle, this method may be used for other infections.     

The Dantu erythrocyte phenotype of the NE variety. I. Dodecylsulfate polyacrylamide gel electrophoretic studies

Red cell membranes from patient NE, Mr. Dantu and 16 additional Black individuals, positive for the low-frequency MNSs-system antigen Dantu, were studied by dodecylsulfate polyacrylamide gel electrophoretic techniques. The content of the major, blood group M- or N-active sialoglycoprotein (glycophorin A, GP A) was found to be decreased by about 57%. The blood group S- or s-active sialoglycoprotein (GP B) was decreased by about 51% in membranes from proven Dantu/U heterozygotes and not detectable in those from patient NE and other Dantu+U- individuals. Donor NE was shown to exhibit the genotype Dantu/u. Dantu-positive cells exhibit a proteinase-resistant GP B-GP A hybrid with an apparent molecular mass of 29 KDa whose intramembraneous and cytoplasmic domains were shown to be similar to those of GP A. The molar hybrid: GP A ratio in all cells was found to be about 2.4: 1, indicating that the NE variety of the Dantu phenotype is much more frequent than the Ph or MD types. The significance of an additional minor 'new' component (molecular mass 21 KDa) in Dantu+ membranes and the minor component J (molecular mass 22 KDa) occurring in normal and Dantu+U+ GP preparations, but not in those from Dantu+U- cells, has not been resolved. The apparent molecular mass of the anion channel protein (band 3) in all cells of the NE variety was shown to be decreased by about 3 KDa, due to a shortening of carbohydrate chains. This suggests that the hybrid, just like GP A, might form a complex with band 3.     

Canine erythrocyte pyruvate kinase. I. Properties of the normal enzyme

We have compared the kinetic, immunological, and electrophoretic properties of human and canine erythrocyte pyruvate kinase. Both enzymes are allosteric and subject to positive and negative regulation. The allosteric properties of the canine enzyme are more pronounced than those of the human enzyme; however, the properties of both enzymes are consistent with a regulatory function in the glycolytic pathway of their respective erythrocytes. Antiserum against the human enzyme gives precipitin lines of partial identity between the human and canine enzymes on immunodiffusion. The anti-human serum inactivates the enzymatic activity of both enzymes, although it is more effective against the human enzyme than the canine. The two enzymes have slightly different mobilities on starch gel electrophoresis. While we have demonstrated differences between erythrocyte pyruvate kinase from dogs and that from humans, we conclude that the enzymes are sufficiently similar in properties and function to allow use of the dog as a model for human erythrocyte pyruvate kinase deficiency.