Chronic intermittent hypoxia-induced vascular enlargement and VEGF upregulation in the rat carotid body is not prevented by antioxidant treatment

Chronic intermittent hypoxia (CIH), a characteristic of sleep obstructive apnea, enhances carotid body (CB) chemosensory responses to hypoxia, but its consequences on CB vascular area and VEGF expression are unknown. Accordingly, we studied the effect of CIH on CB volume, glomus cell numbers, blood vessel diameter and number, and VEGF immunoreactivity (VEGF-ir) in male Sprague-Dawley rats exposed to 5% O(2), 12 times/h for 8 h or sham condition for 21 days. We found that CIH did not modify the CB volume or the number of glomus cells but increased VEGF-ir and enlarged the vascular area by increasing the size of the blood vessels, whereas the number of the vessels was unchanged. Because oxidative stress plays an essential role in the CIH-induced carotid chemosensory potentiation, we tested whether antioxidant treatment with ascorbic acid may impede the vascular enlargement and the VEGF upregulation. Ascorbic acid, which prevents the CB chemosensory potentiation, failed to impede the vascular enlargement and the increased VEGF-ir. Thus present results suggest that the CB vascular enlargement induced by CIH is a direct effect of intermittent hypoxia and not secondary to the oxidative stress. Accordingly, the subsequent capillary changes may be secondary to the mechanisms involved in the neural chemosensory plasticity induced by intermittent hypoxia.     

The histone demethylases Jhdm1a/1b enhance somatic cell reprogramming in a vitamin-C-dependent manner

Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) resets the epigenome to an embryonic-like state. Vitamin C enhances the reprogramming process, but the underlying mechanisms are unclear. Here we show that the histone demethylases Jhdm1a/1b are key effectors of somatic cell reprogramming downstream of vitamin C. We first observed that vitamin C induces H3K36me2/3 demethylation in mouse embryonic fibroblasts in culture and during reprogramming. We then identified Jhdm1a/1b, two known vitamin-C-dependent H3K36 demethylases, as potent regulators of reprogramming through gain- and loss-of-function approaches. Furthermore, we found that Jhdm1b accelerates cell cycle progression and suppresses cell senescence during reprogramming by repressing the Ink4/Arf locus. Jhdm1b also cooperates with Oct4 to activate the microRNA cluster 302/367, an integral component of the pluripotency machinery. Our results therefore reveal a role for H3K36me2/3 in cell fate determination and establish a link between histone demethylases and vitamin-C-induced reprogramming.     

The above-ground coarse wood productivity of 104 Neotropical forest plots

The net primary production of tropical forests and its partitioning between long‐lived carbon pools (wood) and shorter‐lived pools (leaves, fine roots) are of considerable importance in the global carbon cycle. However, these terms have only been studied at a handful of field sites, and with no consistent calculation methodology. Here we calculate above‐ground coarse wood carbon productivity for 104 forest plots in lowland New World humid tropical forests, using a consistent calculation methodology that incorporates corrections for spatial variations in tree‐size distributions and wood density, and for census interval length. Mean wood density is found to be lower in more productive forests. We estimate that above‐ground coarse wood productivity varies by more than a factor of three (between 1.5 and 5.5 Mg C ha^?1 a^?1) across the Neotropical plots, with a mean value of 3.1 Mg C ha^?1 a^?1. There appear to be no obvious relationships between wood productivity and rainfall, dry season length or sunshine, but there is some hint of increased productivity at lower temperatures. There is, however, also strong evidence for a positive relationship between wood productivity and soil fertility. Fertile soils tend to become more common towards the Andes and at slightly higher than average elevations, so the apparent temperature/productivity relationship is probably not a direct one. Coarse wood productivity accounts for only a fraction of overall tropical forest net primary productivity, but the available data indicate that it is approximately proportional to total above‐ground productivity. We speculate that the large variation in wood productivity is unlikely to directly imply an equivalent variation in gross primary production. Instead a shifting balance in carbon allocation between respiration, wood carbon and fine root production seems the more likely explanation.     

Experiencia con el uso del registrador implantable de eventos en una serie de personas mayores con caídas y sospecha de síncopes de origen arrítmico

Objective

To review our experience on using an implantable loop recorder (ILR) in patients with recurrent falls, when an arrhythmogenic cause is suspected.

Material and methods

This is a retrospective, observational study of patients with repetitive unexplained falls, suspected syncope, or electrocardiographic abnormalities. All of them had been evaluated by a cardiologist, who decided to implant a loop recorder (ILR) for an accurate diagnosis.

Results

A total of 13 patients received an ILR. The average falls rate for the sample was 3.3. The mean age was 78 years, and 46% were female, with a mean follow-up period of 24 months. During this time, three patients did not suffer from a new fall. An arrhythmogenic diagnosis was obtained in 5 patients: bradycardia was identified in 4 cases, and tachycardia in one of them. The symptoms did not coincide with a documented arrhythmia in the rest of the patients.

Conclusion

ILR is a helpful tool to establish an arrhythmogenic cause of unexplained and recurrent falls, in this selected sample of older adults.     

The bacteriophage phi 29 DNA polymerase, a proofreading enzyme.

The bacteriophage phi 29 DNA polymerase, involved both in the protein-primed initiation and elongation steps of the viral DNA replication, displays a very processive 3',5'-exonuclease activity acting preferentially on single-stranded DNA. This exonucleolytic activity showed a marked preference for excision of a mismatched versus a correctly paired 3' terminus. These characteristics enable the phi 29 DNA polymerase to act as a proofreading enzyme. A comparative analysis of the wild-type phi 29 DNA polymerase and a mutant lacking 3',5'-exonuclease activity indicated that a productive coupling between the exonuclease and polymerase activities is necessary to prevent fixation of polymerization errors. Based on these data, the phi 29 DNA polymerase, a model enzyme for protein-primed DNA replication, appears to share the same mechanism for the editing function as that first proposed for T4 DNA polymerase and Escherichia coli DNA polymerase I on the basis of functional and structural studies.     

Infraciliature, morphogenesis and life cycle of Endosphaera terebrans (Suctoria, Tokophridae)

The morphology, infraciliature, and life cycle of Endosphaera terebrans, a suctorian endocommensal of peritrichs, have been studied with the aid of silver impregnation. The life cycle of Endosphaera terebrans begins with infection of the host cell by a small larva. The swarmer has a pointed needle-like cellular projection and two rings of cilia. The swarmer penetrates the the peritrich, loses the cilia, and then matures into an adult. The infraciliature of the adult form has four rows of barren kinetosomes that lack kinetodesmal fibers. By endogenous budding, a migratory larva is produced that leaves the host cell through the peristomial disc and that can infect other peritrichs.     

Characterization of the gene encoding pisatin demethylase (FoPDA1) in Fusarium oxysporum

The pea pathogen Fusarium oxysporum f. sp. pisi is able to detoxify pisatin produced as a defense response by pea, and the gene encoding this detoxification mechanism, FoPDA1, was 82% identical to the cytochrome P450 pisatin demethylase PDA1 gene in Nectria haematococca. A survey of F. oxysporum f. sp. pisi isolates demonstrated that, as in N. haematococca, the PDA gene of F. oxysporum f. sp. pisi is generally located on a small chromosome. In N. haematococca, PDA1 is in a cluster of pea pathogenicity (PEP) genes. Homologs of these PEP genes also were found in the F. oxysporum f. sp. pisi isolates, and PEP1 and PEP5 were sometimes located on the same small chromosomes as the FoPDA1 homologs. Transforming FoPDA1 into a pda(?) F. oxysporum f. sp. lini isolate conferred pda activity and promoted pathogenicity on pea to some transformants. Different hybridization patterns of FoPDA1 were found in F. oxysporum f. sp. pisi but these did not correlate with the races of the fungus, suggesting that races within this forma specialis arose independently of FoPDA1. FoPDA1 also was present in the formae speciales lini, glycines, and dianthi of F. oxysporum but they had mutations resulting in nonfunctional proteins. However, an active FoPDA1 was present in F. oxysporum f. sp. phaseoli and it was virulent on pea. Despite their evolutionary distance, the amino acid sequences of FoPDA1 of F. oxysporum f. sp. pisi and F. oxysporum f. sp. phaseoli revealed only six amino acid differences, consistent with a horizontal gene transfer event accounting for the origin of these genes.     

Categorization of humans in biomedical research: genes,race and disease

A debate has arisen regarding the validity of racial/ethnic categories for biomedical and genetic research. Some claim 'no biological basis for race' while others advocate a 'race-neutral' approach, using genetic clustering rather than self-identified ethnicity for human genetic categorization. We provide an epidemiologic perspective on the issue of human categorization in biomedical and genetic research that strongly supports the continued use of self-identified race and ethnicity.     

Glucocorticoid alternative effects on proliferating and differentiated mammary epithelium are associated to opposite regulation of cell-cycle inhibitor expression

Glucocorticoids influence post-natal mammary gland development by sequentially controlling cell proliferation, differentiation, and apoptosis. In the mammary gland, it has been demonstrated that glucocorticoid treatment inhibits epithelial apoptosis in post-lactating glands. In this study, our first goal was to identify new glucocorticoid target genes that could be involved in generating this effect. Expression profiling, by microarray analysis, revealed that expression of several cell-cycle control genes was altered by dexamethasone (DEX) treatment after lactation. Importantly, it was determined that not only the exogenous synthetic hormone, but also the endogenous glucocorticoids regulated the expression of these genes. Particularly, we found that the expression of cell cycle inhibitors p21CIP1, p18INK4c, and Atm was differentially regulated by glucocorticoids through the successive stages of mammary gland development. In undifferentiated cells, DEX treatment induced their expression and reduced cell proliferation, while in differentiated cells this hormone repressed expression of those cell cycle inhibitors and promoted survival. Therefore, differentiation status determined the effect of glucocorticoids on mammary cell fate. Particularly, we have determined that p21CIP1 inhibition would mediate the activity of these hormones in differentiated mammary cells because over-expression of this protein blocked DEX-induced apoptosis protection. Together, our data suggest that the multiple roles played by glucocorticoids in mammary gland development and function might be at least partially due to the alternative roles that these hormones play on the expression of cell cycle regulators.