Sex-chromosome aberrations in wood lemmings (Myopus schisticolor)

The wood lemming displays certain peculiar features: (1) The sex ratio shows a prevalence of females (FRANK, 1966; KALELA and OKSALA, 1966), and some females produce only female offspring (KALELA and OKSALA, 1966). (2) In a considerable proportion (in the present material, slightly less than half) of the females, an XY chromosome complement is found in the somatic tissues, but the Y is absent in the germ line of those studied (Fredga et al., 1976). Therefore, (3) a mechanism of double nondisjunction in early fetal life of XY females has to be postulated, which replaces the Y in the germ line by duplication of the X. It is assumed (4) that the X of XY females bears a sex-reversal factor that affects the male determining action of the Y (Fredga et al., 1977). There is (5) a strong presumption that in most cases the XY females are those that produce daughters only, but (6) a few exceptions may occur (FRANK, unpublished observations), suggesting that the regulation according to assumption 3 (perhaps also to 4) is incomplete in XY females. In the present report, four females are described with a 31,XO karyotype, two females with 33,XYY or 32,XY/33,XYY, respectively, two males with a 33,XXY, and one male with a 32,XX/33,XXY karyotype, as observed in a consecutive series of 502 wood lemmings. The incidence of sex-chromosome anomalies in liveborn and adult animals was 2.3%; the overall incidence, including embryos, was 1.79%. Neither the somatic XO constitution nor the existence of an extra Y in females precludes fertility. However, the XXY condition in the male results in sterility. There is certain evidence that an instability of the proposed mechanism for double mitotic nondisjunction of the sex chromosomes in oogonia accounts for the high rate of sex-chromosome aberrations in wood lemmings, at least when the mother is XY.     

Improved chemical synthesis and enzymatic assay of delta-1-pyrroline-5-carboxylic acid.

Δ¹-Pyrroline-5-car?ylic acid, an intermediate in both the biosynthesis and degradation ofl-proline, has been synthesized by the periodate oxidation of hydroxylysine and isolated as a pure compound, as indicated by enzymatic assay with pyrroline-5-car?ylate reductase fromEscherichia coli. Some features of the instability in solution ofΔ¹-pyrroline-5-car?ylic acid have been studied, leading to the conclusion that the rate of decomposition is sensitive to concentration of the compound. Colorimetric assay witho-aminobenzaldehyde was found to be an inadequate measure of the pyrroline compound in partially decomposed solutions.     

A mathematical biothermal model of the california sea lion

The thermal behavior of the California sea lion is modeled by a set of seventeen simultaneous partial differential equations. Numerical solution of these equations yields temperature profiles in the sea lion that closely reproduce experimental data obtained with the animals at rest in air. The model predicts that exercise is necessary to maintain body temperature while immersed in very cold water (0°C) but that very efficient heat conservation occurs during diving because of bradycardia, limited circulation, and absence of respiration.     

Genome size distributions in bacteria and archaea are strongly linked to evolutionary history at broad phylogenetic scales

The evolutionary forces that determine genome size in bacteria and archaea have been the subject of intense debate over the last few decades. Although the preferential loss of genes observed in prokaryotes is explained through the deletional bias, factors promoting and preventing the fixation of such gene losses often remain unclear. Importantly, statistical analyses on this topic typically do not consider the potential bias introduced by the shared ancestry of many lineages, which is critical when using species as data points because of the potential dependence on residuals. In this study, we investigated the genome size distributions across a broad diversity of bacteria and archaea to evaluate if this trait is phylogenetically conserved at broad phylogenetic scales. After model fit, Pagel’s lambda indicated a strong phylogenetic signal in genome size data, suggesting that the diversification of this trait is influenced by shared evolutionary histories. We used a phylogenetic generalized least-squares analysis (PGLS) to test whether phylogeny influences the predictability of genome size from dN/dS ratios and 16S copy number, two variables that have been previously linked to genome size. These results confirm that failure to account for evolutionary history can lead to biased interpretations of genome size predictors. Overall, our results indicate that although bacteria and archaea can rapidly gain and lose genetic material through gene transfers and deletions, respectively, phylogenetic signal for genome size distributions can still be recovered at broad phylogenetic scales that should be taken into account when inferring the drivers of genome size evolution.     

Dispersal polymorphisms in subdivided populations

Price's method for analyzing natural selection in subdivided populations is applied to the problem of dispersal polymorphism strategies in a stable habitat. The results agree with the more traditional Mendelian models for this same problem that have recently been published. Further, by using Price's method, the results obtained are simpler and more general, and the causal evolutionary mechanisms underlying the predicted patterns are more easily recognized. The most interesting new result is that the equilibrium proportion of dispersed individuals is a simple function of the risk of dispersing and the regression coefficient of relatedness among individuals who, in the absence of dispersal, would compete for a limited, local resource. This regression coefficient refers to the genotypes that control the dispersal phenotype. For example, when mothers control the phenotype of their progeny, then the regression is from the mother onto an offspring chosen randomly from the local group before dispersal; while when offspring control their own phenotype, the regression is taken directly from offspring onto a randomly chosen cohort member before dispersal. This use of controlling genotypes to calculate regressions explains the form of the parent-offspring conflict over dispersal noted by previous authors. The simplicity and generality of these results suggest that Price's method is a useful approach for studying the class of phenomena known as "games among relatives".     

Effect of apolipoprotein A-I lipidation on the formation and function of pre-beta and alpha-migrating LpA-I particles

A unique class of lipid-poor high-density lipoprotein, pre-beta1 HDL, has been identified and shown to have distinct functional characteristics associated with intravascular cholesterol transport. In this study we have characterized the structure/function properties of poorly lipidated HDL particles and the factors that mediate their conversion into multimolecular lipoprotein particles. Studies were undertaken with homogeneous recombinant HDL particles (LpA-I) containing apolipoprotein (apo) A-I and various amounts of palmitoyloleoylphosphatidylcholine (PC) and cholesterol. Complexation of apoA-I with small amounts of PC and cholesterol results in the formation of discrete lipoprotein structures that have a hydrated diameter of about 6 nm but contain only one molecule of apoA-I (Lp1A-I). While the molecular charge and alpha-helix content of apoA-I are unaffected by lipidation, the thermodynamic stability of the protein is reduced significantly (from 2.4 to 0.9 kcal/mol of apoA-I). Evaluation of apoA-I conformation by competitive radioimmunoassay with monoclonal antibodies shows that addition of small amounts of PC and cholesterol to apoA-I significantly increases the immunoreactivity of a number of domains over the entire molecule. Increasing the ratio of PC:apoA-I to 10:1 in the Lp1A-I complex is associated with increases in the alpha-helix content and stability of apoA-I. However, incorporation of 10-15 mol of PC destabilizes the Lp1A-I complex and promotes the formation of more thermodynamically stable (1.8 kcal/mol of apoA-I) bimolecular structures (Lp2A-I) that are approximately 8 nm in diameter. The formation of an Lp2A-I particle is associated with an increased immunoreactivity of most of the epitopes studied, with the exception of one central domain (residues 98-121), which becomes significantly less exposed. This structural change parallels a significant increase in the net negative charge on the complex. Characterization of the ability of these lipoproteins to act as substrates for lecithin:cholesterol acyltransferase (LCAT) shows that unstable Lp1A-I complexes stimulate a higher rate of cholesterol esterification by LCAT than the small but more stable Lp2A-I particles (Vmax values are 5.8 and 0.3 nmol of free cholesterol esterified/h, respectively). The ability of LCAT to interact with lipid-poor apoA-I suggests that LCAT does not need to bind to the lipid interface on an HDL particle but that LCAT may directly interact with apoA-I. The data suggests that lipid-poor HDL particles may be metabolically reactive particles because they are thermodynamically unstable.     

Cancer stem cells and human malignant melanoma

Cancer stem cells (CSC) have been identified in hematological malignancies and several solid cancers. Similar to physiological stem cells, CSC are capable of self-renewal and differentiation and have the potential for indefinite proliferation, a function through which they may cause tumor growth. Although conventional anti-cancer treatments might eradicate most malignant cells in a tumor, they are potentially ineffective against chemoresistant CSC, which may ultimately be responsible for recurrence and progression. Human malignant melanoma is a highly aggressive and drug-resistant cancer. Detection of tumor heterogeneity, undifferentiated molecular signatures, and increased tumorigenicity of melanoma subsets with embryonic-like differentiation plasticity strongly suggest the presence and involvement of malignant melanoma stem cells (MMSC) in the initiation and propagation of this malignancy. Here, we review these findings in the context of functional properties ascribed to melanocyte stem cells and CSC in other cancers. We discuss the association of deregulated signaling pathways, genomic instability, and vasculogenic mimicry phenomena observed in melanoma subpopulations in light of the CSC concept. We propose that a subset of MMSC may be responsible for melanoma therapy-resistance, tumor invasiveness, and neoplastic progression and that targeted abrogation of a MMSC compartment could therefore ultimately lead to stable remissions and perhaps cures of metastatic melanoma.