Genetic Controls over Activities of Tyrosinase and Dopachrome Conversion Factor in Murine Melanocytes

We evaluated the three catalytic activities of tyrosinase and one activity of dopachrome conversion factor (DCF) in extracts made from skins of 6-day-old yellow and nonyellow mice. At least one of the catalytic activities of tyrosinase and of DCF correlate with the color of pigment being produced in the hair follicles of the mice. We use these data to evaluate existing hypotheses about the mechanism of the interacting genetic controls over melanogenesis.     

Genetic Studies of the Mouse Mutations Mahogany and Mahoganoid

The mouse mutations mahogany (mg) and mahoganoid (md) are negative modifiers of the Agouti coat color gene, which encodes a paracrine signaling molecule that induces a switch in melanin synthesis from eumelanin to pheomelanin. Animals mutant for md or mg synthesize very little or no pheomelanin depending on Agouti gene background. The Agouti protein is normally expressed in the skin and acts as an antagonist of the melanocyte receptor for α-MSH (Mc1r); however, ectopic expression of Agouti causes obesity, possibly by antagonizing melanocortin receptors expressed in the brain. To investigate where md and mg lie in a genetic pathway with regard to Agouti and Mc1r signaling, we determined the effects of these mutations in animals that carried either a loss-of-function Mc1r mutation (recessive yellow, Mc1r(e)) or a gain-of-function Agouti mutation (lethal yellow, A(y)). We found that the Mc1r(e) mutation suppressed the effects of md and mg, but that md and mg suppressed the effects of A(y) on both coat color and obesity. Plasma levels of α-MSH and of ACTH were unaffected by md or mg. These results suggest that md and mg interfere directly with Agouti signaling, possibly at the level of protein production or receptor regulation.     

The vit gene maps to the mi (microphthalmia) locus of the laboratory mouse.

The murine model for human vitiligo (the vit/vit mouse) develops progressive depigmentation of the pelage, skin, and eyes. The vit gene is inherited as an autosomal recessive. We have used classical breeding and isozyme marker analysis to map this vit gene that produces a vitiligo-like condition in the mouse. Crossbreeding the C57BL/6J-vit/vit mice with C57BL/6J mice carrying the Miwh and/or miws alleles at the microphthalmia locus resulted in mutant phenotypes, demonstrating absence of complementation. When vit is heterozygous with the Miwh allele, a "blotched" pigment pattern results. When it is heterozygous with the miws allele, a novel expression of the vitiliginous phenotype results. Further mating analysis of these crossbred populations demonstrates allelic inheritance between vit and the alleles at the microphthalmia locus. Other breeding studies using alleles at the agouti, belted, brown, dominant spotting, extension, mahogany, patch, and piebald loci did not demonstrate pigmentation explainable by allelic inheritance with the vit gene. Also, vit was tested for linkage with isozyme markers located on chromosomes 1, 4, 5, 7, 9, and 11, and results were negative. Therefore, the vit (vitiligo) gene of the laboratory mouse has been mapped to the mi (microphthalmia) locus on chromosome 6. The gene properly should be designated as mivit.     

Differential response of cycling and noncycling cells to inducers of DNA synthesis and mitosis

The objective of this study was to determine whether cells in G(0) phase are functionally distinct from those in G(1) with regard to their ability to respond to the inducers of DNA synthesis and to retard the cell cycle traverse of the G(2) component after fusion. Synchronized populations of HeLa cells in G(1) and human diploid fibroblasts in G(1) and G(0) phases were separately fused using UV-inactivated Sendai virus with HeLa cells prelabeled with [(3)H]ThdR and synchronized in S or G(2) phases. The kinetics of initiation of DNA synthesis in the nuclei of G(0) and G(1) cells residing in G(0)/S and G(1)/S dikaryons, respectively, were studied as a function of time after fusion. In the G(0)/G(2) and G(1)/G(2) fusions, the rate of entry into mitosis of the heterophasic binucleate cells was monitored in the presence of Colcemid. The effects of protein synthesis inhibition in the G(1) cells, and the UV irradiation of G(0) cells before fusion, on the rate of entry of the G(2) component into mitosis were also studied. The results of this study indicate that DNA synthesis can be induced in G(0)nuclei after fusion between G(0)- and S-phase cells, but G(0) nuclei are much slower than G(1) nuclei in responding to the inducers of DNA synthesis because the chromatin of G(0) cells is more condensed than it is in G(1) cells. A more interesting observation resulting from this study is that G(0) cells is more condensed than it is in G(1) cells. A more interesting observation resulting from this study is that G(0) cells differ from G(1) cells with regard to their effects on the cell cycle progression of the G(2) nucleus into mitosis. This difference between G(0) and G(1) cells appears to depend on certain factors, probably nonhistone proteins, present in G(1) cells but absent in G(0) cells. These factors can be induced in G(0) cells by UV irradiation and inhibited in G(1) cells by cycloheximide treatment.     

Exercise training in childhood-onset systemic lupus erythematosus: a controlled randomized trial

Introduction

Exercise training has emerged as a promising therapeutic strategy to counteract physical dysfunction in adult systemic lupus erythematosus. However, no longitudinal studies have evaluated the effects of an exercise training program in childhood-onset systemic lupus erythematosus (C-SLE) patients. The objective was to evaluate the safety and the efficacy of a supervised aerobic training program in improving the cardiorespiratory capacity in C-SLE patients.

Methods

Nineteen physically inactive C-SLE patients were randomly assigned into two groups: trained (TR, n = 10, supervised moderate-intensity aerobic exercise program) and non-trained (NT, n = 9). Gender-, body mass index (BMI)- and age-matched healthy children were recruited as controls (C, n = 10) for baseline (PRE) measurements only. C-SLE patients were assessed at PRE and after 12 weeks of training (POST). Main measurements included exercise tolerance and cardiorespiratory measurements in response to a maximal exercise (that is, peak VO₂, chronotropic reserve (CR), and the heart rate recovery (ΔHRR) (that is, the difference between HR at peak exercise and at both the first (ΔHRR1) and second (ΔHRR2) minutes of recovery after exercise).

Results

The C-SLE NT patients did not present changes in any of the cardiorespiratory parameters at POST (P > 0.05). In contrast, the exercise training program was effective in promoting significant increases in time-to-exhaustion (P = 0.01; ES = 1.07), peak speed (P = 0.01; ES = 1.08), peak VO₂ (P = 0.04; ES = 0.86), CR (P = 0.06; ES = 0.83), and in ΔHRR1 and ΔHRR2 (P = 0.003; ES = 1.29 and P = 0.0008; ES = 1.36, respectively) in the C-SLE TR when compared with the NT group. Moreover, cardiorespiratory parameters were comparable between C-SLE TR patients and C subjects after the exercise training intervention, as evidenced by the ANOVA analysis (P > 0.05, TR vs. C). SLEDAI-2K scores remained stable throughout the study.

Conclusion

A 3-month aerobic exercise training was safe and capable of ameliorating the cardiorespiratory capacity and the autonomic function in C-SLE patients.

Trial registration

NCT01515163.     

Putting beta-diversity on the map: broad-scale congruence and coincidence in the extremes

Beta-diversity, the change in species composition between places, is a critical but poorly understood component of biological diversity. Patterns of beta-diversity provide information central to many ecological and evolutionary questions, as well as to conservation planning. Yet beta-diversity is rarely studied across large extents, and the degree of similarity of patterns among taxa at such scales remains untested. To our knowledge, this is the first broad-scale analysis of cross-taxon congruence in beta-diversity, and introduces a new method to map beta-diversity continuously across regions. Congruence between amphibian, bird, and mammal beta-diversity in the Western Hemisphere varies with both geographic location and spatial extent. We demonstrate that areas of high beta-diversity for the three taxa largely coincide, but areas of low beta-diversity exhibit little overlap. These findings suggest that similar processes lead to high levels of differentiation in amphibian, bird, and mammal assemblages, while the ecological and biogeographic factors influencing homogeneity in vertebrate assemblages vary. Knowledge of beta-diversity congruence can help formulate hypotheses about the mechanisms governing regional diversity patterns and should inform conservation, especially as threat from global climate change increases.     

The color loci of mice--a genetic century

Color loci in mammals are those genetic loci in which mutations can affect pigmentation of the hair, skin, and/or eyes. In the mouse, over 800 phenotypic alleles are now known, at 127 identified color loci. As the number of color loci passed 100 only recently, we celebrate this 'century' with an overview of these loci, especially the 59 that have been cloned and sequenced. These fall into a number of functional groups representing melanocyte development and differentiation, melanosomal components, organelle biogenesis, organelle transport, control of pigment-type switching, and some systemic effects. A human ortholog has been identified in all cases, and the majority of these human genes are found to be loci for human disorders, often affecting other body systems as well as pigmentation. We expect that a significant number of color loci remain to be identified. Nonetheless, the large number known already provide a treasury of resources for reconstruction of the mechanisms, at the subcellular, cellular and tissue levels, that produce a functional pigmentary system and contribute to the normal development and functioning of many other organ systems. The mutant mice also provide valuable models for the study of human disease.     

Survival Rate and Enzyme Activities ofLactobacillus acidophilusFollowing Frozen Storage

The ability of two strains of Lactobacillus acidophilus, CRL 640 and CRL 800, to survive and retain their biological activities under frozen storage was determined. Freezing and thawing, as well as frozen storage, damaged the cell membrane, rendering the microorganisms sensitive to sodium chloride and bile salts. Both lactic acid production and proteolytic activity were depressed after 21 days at -20 degreesC, whereas beta-galactosidase activity per cell unit was increased. Cell injury was partially overcome after repair in a salt-rich medium. Copyright 1998 Academic Press.     

The value of the IUCN Red List for conservation

The IUCN Red List of Threatened Species is the most comprehensive resource detailing the global conservation status of plants and animals. The 2004 edition represents a milestone in the four-decade long history of the Red List, including the first Global Amphibian Assessment and a near doubling in assessed species since 2000. Moreover, the Red List assessment process itself has developed substantially over the past decade, extending the value of the Red List far beyond the assignation of threat status. We highlight here how the Red List, in conjunction with the comprehensive data compiled to support it and in spite of several important limitations, has become an increasingly powerful tool for conservation planning, management, monitoring and decision making.