Exercise flow-volume loops in prepubescent aerobically trained children.

We studied mechanical ventilatory constraints in 13 aerobically trained (Tr) and 11 untrained (UT) prepubescent children by plotting the exercise flow-volume (F-V) loops within the maximal F-V loop (MFVL) measured at rest. The MFVL allowed to determine forced vital capacity (FVC) and maximal expiratory flows. Expiratory and inspiratory reserve volumes relative to FVC (ERV/FVC and IRV/FVC, respectively) were measured during a progressive exercise test until exhaustion. Breathing reserve (BR) and expiratory flow limitation (expFL), expressed in percentage of tidal volume (V(T)) and defined as the part of the tidal breath meeting the boundary of the MFVL, were measured. Higher FVC and maximal expiratory flows were found in Tr than UT (P < 0.05) at rest. Our results have shown that during exercise, excepting one subject, all Tr regulated their V(T) within FVC similarly during exercise, by breathing at low lung volume at the beginning of exercise followed breathing at high lung volume at strenuous exercise. In UT, ERV/FVC and IRV/FVC were regulated during exercise in many ways. The proportion of children who presented an expFL was nearly the same in both groups (approximately 70% with a range of 14 to 65% of V(T)), and no significant difference was found during exercise concerning expFL. However, higher ventilation (V(E)), ERV/FVC, and dyspnea associated with lower BR, IRV/FVC, and SaO2 were reported at peak power in Tr than UT (P < 0.05). These results suggest that, because of their higher Ve level, trained children presented higher ventilatory constraints than untrained. These may influence negatively the SaO2 level and dyspnea during strenuous exercise.     

Molecular dynamics study of the metallochaperone Hah1 in its apo and Cu(I)-loaded states: role of the conserved residue M10

Molecular dynamics simulations were performed on both apo and copper forms of the human copper chaperone, Hah1. Wild-type Hah1 and a methionine (M10) to serine mutant were investigated. We have evidenced the central role of residue M10 in stabilizing the hydrophobic core of Hah1 as well as the internal structure of the metal-binding site. When copper(I) is bound, the mobility of Hah1 is reduced whereas mutation of M10 implies a drastic increase of the mobility of apoHah1, stressing the importance of this highly conserved hydrophobic residue for copper sequestration by the apoprotein.     

The Caenorhabditis elegans FancD2 ortholog is required for survival following DNA damage

Fanconi anemia (FA) is an autosomal recessive disease characterized by bone-marrow failure, congenital abnormalities, and cancer susceptibility. There are 11 FA complementation groups in human where 8 genes have been identified. We found that FancD2 is conserved in evolution and present in the genome of the nematode Caenorhabditis elegans. The gene Y41E3.9 (CeFancD2) encodes a structural ortholog of human FANCD2 and is composed of 10 predicted exons. Our analysis showed that exons 6 and 7 were absent from a CeFancD2 EST suggesting the presence of a splice variant. In an attempt to characterize its role in DNA damage, we depleted worms of CeFANCD2 using RNAi. When the CeFANCD2(RNAi) worms were treated with a crosslinking agent, a significant drop in the progeny survival was noted. These worms were also sensitive, although to a lesser extent, to ionizing radiation (IR). Therefore, these data support an important role for CeFANCD2 in DNA damage response as for its human counterpart. The data also support the usefulness of C. elegans to study the Fanconi anemia pathway, and emphasize the biological importance of FANCD2 in DNA damage response throughout evolution.     

Catalytic and DNA-binding properties of the human Ogg1 DNA N-glycosylase/AP lyase: biochemical exploration of H270, Q315 and F319, three amino acids of the 8-oxoguanine-binding pocket

The human Ogg1 protein (hOgg1) is an antimutator DNA glycosylase/AP lyase that catalyzes the excision of 8-oxo-7,8-dihydroguanine (8-oxoG) and the incision of apurinic and apyrimidinic (AP) sites in DNA. In this study, we have investigated the functional role of H270, Q315 and F319, three amino acids that are located in the 8-oxoG-binding pocket of hOgg1. Wild-type and mutant hOgg1 proteins (H270A, H270R, H270L, Q315A and F319A) were purified to apparent homogeneity. The catalytic activities and the DNA-binding properties of the various hOgg1 mutants were compared to those of the wild-type. The results show that hOgg1 mutated at H270 (H270A and H270L) or F319 (F319A) exhibits greatly reduced (50- to 1000-fold) DNA glycosylase activity, whereas the AP lyase activity is only moderately affected (<4-fold). The affinity of the hOgg1 mutants (H270A, H270L and F319A) for 8-oxoG.C-containing DNA is also greatly reduced (>30-fold), whereas their affinity for THF.C-containing DNA is only moderately reduced (<7-fold). The results also show that hOgg1 mutated at Q315 (Q315A) exhibits catalytic and DNA-binding properties similar to those of the wild-type. Therefore, H270 and F319 are essential to form the functional 8-oxoG-binding pocket, whereas Q315 is less crucial. In contrast, H270, Q315 and F319 are not required for efficient binding of THF.C and cleavage of AP sites. Finally, hOgg1 mutant proteins with a substitution of H270A or F319A are members of a new type of hOgg1 that is deficient in DNA glycosylase but proficient in AP lyase.     

Distribution and abundance of parasite nematodes: ecological specialisation,phylogenetic constraint or simply epidemiology?

We investigate the patterns of abundance‐spatial occupancy relationships of adult parasite nematodes in mammal host populations (828 populations of nematodes from 66 different species of terrestrial mammals). A positive relationship between mean parasite abundance and host occupancy, i.e. prevalence, is found which suggests that local abundance is linked to spatial distribution across species. Moreover, the frequency distribution of the parasite prevalence is bimodal, which is consistent with a core‐satellite species distribution. In addition, a strong positive relationship between the abundance (log‐transformed) and its variance (log‐transformed) is observed, the distribution of worm abundance being lognormally distributed when abundance values have been corrected for host body size.
Hanski et al. proposed three distinct hypotheses, which might account for the positive relationship between abundance and prevalence in free and associated organisms: 1) ecological specialisation, 2) sampling artefact, and 3) metapopulation dynamics. In addition, Gaston and co‐workers listed five additional hypotheses. Four solutions were not applicable to our parasitological data due to the lack of relevant information in most host‐parasite studies. The fifth hypothesis, i.e. the confounded effects exerted by common history on observed patterns of parasite distributions, was considered using a phylogeny‐based comparison method. Testing the four possible hypotheses, we obtained the following results: 1) the variation of parasite distribution across host species is not due to phylogenetic confounding effects; 2) the positive relationship between mean abundance and prevalence of nematodes may not result from an ecological specialisation, i.e. host specificity, of these parasites; 3) both a positive abundance‐prevalence relationship and a negative coefficient of variation of abundance‐prevalence relationship are likely to occur which corroborates the sampling model developed by Hanski et al. We argue that demographic explanations may be of particular importance to explain the patterns of bimodality of prevalence when testing Monte‐Carlo simulations using epidemiological modelling frameworks, and when considering empirical findings. We conclude that both the bimodal distribution of parasite prevalence and the mean‐variance power function simply result from demographic and stochastic patterns (highlighted by the sampling model), which present compelling evidence that nematode parasite species might adjust their spatial distribution and burden in mammal hosts for simple epidemiological reasons.     

Can different species of medicinal leeches (Hirudo spp.) interbreed?

Abstract. Since the 18th century, the medicinal leech Hirudo medicinalis has been thought to comprise a single species with several different color morphs, but recently some of these color morphs have been assigned to separate species based on morphology, geographical distribution, and molecular sequence data. This research was aimed at testing the ability of three of these species, H. medicinalis, Hirudo verbana, and Hirudo orientalis, to interbreed. We found that in the laboratory, all three species were able to mate with each other and produce hybrid offspring. This suggests that the reproductive isolation is not strong among these species of the genus Hirudo. However, fewer offspring were produced from interspecific crosses compared with intraspecific crosses. This decrease of fecundity (and in some cases, offspring viability) indicates some degree of reproductive isolation between H. medicinalis, H. verbana, and H. orientalis.     

A model of globin evolution

Putative globins have been identified in 426 bacterial, 32 Archaeal and 67 eukaryote genomes. Among these sequences are the hitherto unsuspected presence of single domain sensor globins within Bacteria, Fungi, and a Euryarchaeote. Bayesian phylogenetic trees suggest that their occurrence in the latter two groups could be the result of lateral gene transfer from Bacteria. Iterated psiblast searches based on groups of globin sequences indicate that bacterial flavohemoglobins are closer to metazoan globins than to the other two lineages, the 2-over-2 globins and the globin-coupled sensors. Since Bacteria is the only kingdom to have all the subgroups of the three globin lineages, we propose a working model of globin evolution based on the assumption that all three lineages originated and evolved only in Bacteria. Although the 2-over-2 globins and the globin-coupled sensors recognize flavohemoglobins, there is little recognition between them. Thus, in the first stage of globin evolution, we favor a flavohemoglobin-like single domain protein as the ancestral globin. The next stage comprised the splitting off to single domain 2-over-2 and sensor-like globins, followed by the covalent addition of C-terminal domains resulting in the chimeric flavohemoglobins and globin-coupled sensors. The last stage encompassed the lateral gene transfers of some members of the three globin lineages to specific groups of Archaea and Eukaryotes.     

The intron 7 donor splice site transition: a second Tay-Sachs disease mutation in French Canada

Mutations at the hexosaminidase A (HEXA) gene which cause Tay-Sachs disease (TSD) have elevated frequency in the Ashkenazi Jewish and French-Canadian populations. We report a novel TSD allele in the French-Canadian population associated with the infantile form of the disease. The mutation, a GA transition at the +1 position of intron 7, abolishes the donor splice site. Cultured human fibroblasts from a compound heterozygote for this transition (and for a deletion mutation) produce no detectable HEXA mRNA. The intron 7+1 mutation occurs in the base adjacent to the site of the adult-onset TSD mutation (G805A). In both mutations a restriction site for the endonuclease EcoRII is abolished. Unambiguous diagnosis, therefore, requires allele-specific oligonucleotide hybridization to distinguish between these two mutant alleles. The intron 7+1 mutation has been detected in three unrelated families. Obligate heterozygotes for the intron 7+1 mutation were born in the Saguenay-Lac-St-Jean region of Quebec. The most recent ancestors common to obligate carriers of this mutation were from the Charlevoix region of the province of Quebec. This mutation thus has a different geographic centre of diffusion and is probably less common than the exon 1 deletion TSD mutation in French Canadians. Neither mutation has been detected in France, the ancestral homeland of French Canada.