Microbodies (peroxisomes) in the toad,Bufo marinus

Summary Microbodies (peroxisomes), a group of cytoplasmic organelles enriched in catalase, are demonstrated in the toad, Bufo marinus, by light and electron microscopy by means of a cytochemical staining procedure that demonstrates the peroxidatic activity of catalase with diaminobenzidine (DAB). Amphibian microbodies are similar to those of other classes in their fine structure and localization in hepatocytes and kidney, where they are prominent in the proximal tubular cells. Nucleoids are present only in renal microbodies. In the proximal renal tubule an unusual group of large brown granules are identified as lysosomes by their acid phosphatase, -glucosaminidase and -glucuronidase activities.This work was supported by U.S. Public Health Service Grants Nos. NS-06856 and HD 00674. We wish to thank Dr. Richard M. Hays who generously supplied us with toads; Dr. Alex B. Novikoff for making available facilities for ultramicrotomy, Miss Betty De Prest for technical assistance; Miss Marianne Van Hooren for preparation of the photomicrographs.     

The causes of epistasis in genetic networks

Epistasis refers to the nonadditive interactions between genes in determining phenotypes. Considerable efforts have shown that, even for a given organism, epistasis may vary both in intensity and sign. Recent comparative studies supported that the overall sign of epistasis switches from positive to negative as the complexity of an organism increases, and it has been hypothesized that this change shall be a consequence of the underlying gene network properties. Why should this be the case? What characteristics of genetic networks determine the sign of epistasis? Here we show, by evolving genetic networks that differ in their complexity and robustness against perturbations but that perform the same tasks, that robustness increased with complexity and that epistasis was positive for small nonrobust networks but negative for large robust ones. Our results indicate that robustness and negative epistasis emerge as a consequence of the existence of redundant elements in regulatory structures of genetic networks and that the correlation between complexity and epistasis is a byproduct of such redundancy, allowing for the decoupling of epistasis from the underlying network complexity.     

Respiratory response to chemical stimuli and exercise capacity under conditions of acute hypoxia in elite mountain climbers]

To investigate the factors that modulate exercise performance at extreme altitude, the role of the following variables was analyzed in 16 climbers: 1) ventilatory response to chemical stimuli (hypoxia and hypercapnia); and, 2) maximum exercise performance while breathing room air and during acute hypoxia (F1O2, 0.11). Seven climbers (elite climbers, AE) had previously ascended to 8,000 m or more above sea level, and 9 (A) had never achieved such extreme altitude. Then healthy sedentary subjects (C) of similar age (31.1 +/- 6.0 SD years) were used as control group. Elite climbers showed higher ventilatory responses to both transient hypoxia (-0.49 +/- 0.13 L x min-1 x %-1) (p less than 0.05) and progressive hypoxia (-0.47 +/- 0.13 L x min-1 x %-1) than C (-0.33 +/- 0.14 and -0.30 +/- 0.15 L x min-1 x %-1, respectively). By contrast, no differences were observed between the two groups of climbers. The ventilatory response to hypercapnia was higher in AE (3.04 +/- 1.03 L x min-1 mmHg-1) compared to A (1.85 +/- 0.73 L x min-1 mmHg-1) (p less than 0.05) but similar to that observed in C. Breathing 11% O2, maximum workload and oxyhemoglobin desaturation during maximum exercise were similar in both groups of climbers. Additionally, the ventilatory response to hypoxia did not correlate with maximum workload (F1O2, 0.11), maximal ventilation during exercise (F1O2, 0.11), nor with the altitude score. The present study supports previous reports that inform about the role of the ventilatory response to hypoxia in the exercise performance at high altitude.(ABSTRACT TRUNCATED AT 250 WORDS)     

Platelet-Mediated Metabolism of the Common Dietary Flavonoid,Quercetin

Background

Flavonoid metabolites remain in blood for periods of time potentially long enough to allow interactions with cellular components of this tissue. It is well-established that flavonoids are metabolised within the intestine and liver into methylated, sulphated and glucuronidated counterparts, which inhibit platelet function.

Methodology/Principal Findings

We demonstrate evidence suggesting platelets which contain metabolic enzymes, as an alternative location for flavonoid metabolism. Quercetin and a plasma metabolite of this compound, 4′-O-methyl quercetin (tamarixetin) were shown to gain access to the cytosolic compartment of platelets, using confocal microscopy. High performance liquid chromatography (HPLC) and mass spectrometry (MS) showed that quercetin was transformed into a compound with a mass identical to tamarixetin, suggesting that the flavonoid was methylated by catechol-O-methyl transferase (COMT) within platelets.

Conclusions/Significance

Platelets potentially mediate a third phase of flavonoid metabolism, which may impact on the regulation of the function of these cells by metabolites of these dietary compounds.     

Is retinoic acid genetic machinery a chordate innovation?

Development of many chordate features depends on retinoic acid (RA). Because the action of RA during development seems to be restricted to chordates, it had been previously proposed that the "invention" of RA genetic machinery, including RA-binding nuclear hormone receptors (Rars), and the RA-synthesizing and RA-degrading enzymes Aldh1a (Raldh) and Cyp26, respectively, was an important step for the origin of developmental mechanisms leading to the chordate body plan. We tested this hypothesis by conducting an exhaustive survey of the RA machinery in genomic databases for twelve deuterostomes. We reconstructed the evolution of these genes in deuterostomes and showed for the first time that RA genetic machinery--that is Aldh1a, Cyp26, and Rar orthologs--is present in nonchordate deuterostomes. This finding implies that RA genetic machinery was already present during early deuterostome evolution, and therefore, is not a chordate innovation. This new evolutionary viewpoint argues against the hypothesis that the acquisition of gene families underlying RA metabolism and signaling was a key event for the origin of chordates. We propose a new hypothesis in which lineage-specific duplication and loss of RA machinery genes could be related to the morphological radiation of deuterostomes.     

Analysis of planarian Adh3 supports an intron-rich architecture and tissue-specific expression for the urbilaterian ancestral form

The alcohol dehydrogenase class 3 enzyme (ADH3) is the presumed ancestral form of the medium-chain dehydrogenase-reductase ADH family. This enzyme has been involved in formaldehyde and nitric oxide metabolism of a variety of deuterostomes and ecdysozoan protostomes. We have now characterized the structure and expression of the Adh3 gene in the lophotrochozoan Schmidtea mediterranea, a freshwater planarian. The planarian gene expands over 8.7 kb and is organized into 7 exons. The 1340 bp long Adh3cDNA contains a 1137 bp open reading frame corresponding to a deduced protein of 379 amino acids. The protein sequence is consistent with that expected for a typical class III enzyme. Twenty out of the twenty-two amino acid positions associated with enzymatic roles are strictly preserved, which suggests that the enzymatic capabilities have been conserved. In situ hybridization experiments show that Adh3 is expressed along the intestine of S. mediterranea specimens. This is consistent with the pattern observed in invertebrates and in contrast with the widespread expression of vertebrate Adh3. The comparative study across bilateria, which now includes a lophotrochozoan representative, further supports the idea that the urbilaterian Adh3 ancestor showed an intron-rich architecture and tissue-specific expression, and strengthens the view that widespread expression of Adh3 was a vertebrate innovation.     

Comparaison de la dose efficace en TEP/TDM et en TDM

Hybrid imaging, particularly positron emission tomography (PET) combined with CT has emerged in the field of oncology as a modality of choice. The concomitant realization of a standard CT examination, however, raises the question of the additional dose delivered to the patient. This radiation burden could be avoided by performing a single PET/CT examination with injection of contrast media. To verify the potential dosimetric gain of this strategy, we compared the effective dose associated with each modality in a retrospective cohort of 151 patients, homogeneous in weight and size. The average effective dose for a PET/CT (injection of 5-6 MBq/kg of ¹⁸FDG) was 13.5 mSv, the CT dose representing approximately 80% of the PET dose. In our study, the average effective dose in CT thorax/abdomen/pelvis was 21.4 mSv, 60% higher than the PET/CT effective dose.