The PWAPA cassette: Intimate association of a PHD-like finger and a winged-helix domain in proteins included in histone-modifying complexes

Polycomb complexes function as enforcers of epigenetically repressed state, balanced by an antagonist state mediated by Trithorax. Using sensitive methods of sequence analysis, we show here that Polycomb-like proteins (PCLs) contain a tandem of intimately associated domains, which we named PWAPA and which is also present in ASH2L, a member of the Trithorax group. Polycomb-like proteins and ASH2L belong to the PCR2 and MLL histone methyltransferase complexes, respectively. A PWAPA cassette is also present in ATAC2, a component of the ATAC histone acetyltransferase complex. The recently solved structure of the PWAPA tandem of ASH2L has revealed that it consist in a PHD-like finger followed by a helix-winged-helix (WH) domain, able to bind DNA. The modeling of the 3D structure of the different members of the PWAPA family suggests that the PHD-like finger might be able, at least for some proteins of the family, to bind methylated marks on histones. The PWAPA PHD/WH cassette might thus be involved in the combined recognition of DNA and specific (perhaps methylation) mark(s) on histones, thereby allowing the recruitment of specific chromatin-modifying activities at these sites. The observations reported here should help to unravel the exact role played by the PWAPA cassette in the different proteins of the PWAPA family, and especially in the antagonistic activities of PcG and TrxG proteins.     

Ventilatory and cardiac responses to hypoxia at submaximal exercise are independent of altitude and exercise intensity

The hypoxic exercise test combining a 4,800-m simulated altitude and a cycloergometer exercise at 30% of normoxic maximal aerobic power (MAP) is used to evaluate the individual chemosensitivity to hypoxia in submaximal exercise conditions. This test allows the calculation of three main parameters: the decrease in arterial oxygen saturation induced by hypoxia at exercise (ΔSa(e)) and the ventilatory (HVR(e)) and cardiac (HCR(e)) responses to hypoxia at exercise. The aim of this study was to determine the influence of altitude and exercise intensity on the values of ΔSa(e), HVR(e), and HCR(e). Nine subjects performed hypoxic tests at three simulated altitudes (3,000 m, 4,000 m, and 4,800 m) and three exercise intensities (20%, 30%, and 40% MAP). ΔSa(e) increased with altitude and was higher for 40% MAP than for 20% or 30% (P < 0.05). For a constant heart rate, the loss in power output induced by hypoxia, relative to ΔSa(e), was independent of altitude (4,000-4,800 m) and of exercise intensity. HVR(e) and HCR(e) were independent of altitude (3,000-4,800 m) and exercise intensity (20%-40% MAP). Moreover, the intraindividual variability of responses to hypoxia was lower during moderate exercise than at rest (P < 0.05 to P < 0.001). Therefore, we suggest that HVR(e) and HCR(e) are invariant parameters that can be considered as intrinsic physiological characteristics of chemosensitivity to hypoxia.     

Pds5 promotes cohesin acetylation and stable cohesin-chromosome interaction

Pds5 and Wpl1 act as anti-establishment factors preventing sister-chromatid cohesion until counteracted in S-phase by the cohesin acetyl-transferase Eso1. However, Pds5 is also required to maintain sister-chromatid cohesion in G2. Here, we show that Pds5 is essential for cohesin acetylation by Eso1 and ensures the maintenance of cohesion by promoting a stable cohesin interaction with replicated chromosomes. The latter requires Eso1 only in the presence of Wapl, indicating that cohesin stabilization relies on Eso1 only to neutralize the anti-establishment activity. We suggest that Eso1 requires Pds5 to counteract anti-establishment. This allows both cohesion establishment and Pds5-dependent stable cohesin binding to chromosomes.     

Resveratrol-induced changes of the human adipocyte secretion profile

Enlarged white adipose tissue (WAT) is a feature of obesity and leads to changes in its paracrine and endocrine function. Dysfunction of WAT cells is associated with obesity-associated disorders like type 2 diabetes and cardiovascular diseases. Resveratrol (RSV), a natural polyphenolic compound, mimics beneficial effects of calorie restriction. As such, RSV seems a promising therapeutic target for obesity-associated disorders. The effect of RSV on the human adipokine profile is still elusive. Therefore, a proteomic study together with bioinformatical analysis was performed to investigate the effect of RSV on the secretion profile of mature human SGBS adipocytes. RSV incubation resulted in elevated basal glycerol release and reduced intracellular TG content. This increased intracellular lipolysis was accompanied by profound changes in the adipocyte secretion profile. Extracellular matrix proteins were down-regulated while processing proteins were mostly up-regulated after RSV treatment. Interestingly, RSV induced secretion of proteins protective against cellular stress and proteins involved in the regulation of apoptosis. Furthermore, we found a RSV-induced up-regulation of adiponectin and ApoE accompanied by a down-regulation of PAI-1 and PEDF secretion which may improve anti-inflammatory processes and increased insulin sensitivity. These effects may contribute to alleviate obesity-induced metabolic complications. In addition, two novel RSV-regulated adipocyte-secreted proteins were identified.     

Proteome of Aedes aegypti in response to infection and coinfection with microsporidian parasites

Hosts are frequently infected with more than one parasite or pathogen at any one time, but little is known as to how they respond to multiple immune challenges compared to those involving single infections. We investigated the proteome of Aedes aegypti larvae following infection with either Edhazardia aedis or Vavraia culicis, and coinfections involving both. They are both obligate intracellular parasites belonging to the phylum microsporidia and infect natural populations of Ae. aegypti. The results found some proteins only showing modified abundance in response to infections involving E. aedis, while others were only differentially abundant when infections involved V. culicis. Some proteins only responded with modified abundance to the coinfection condition, while others were differentially abundant in response to all three types of infection. As time since infection increased, the response to each of the single parasite infections diverged, while the response to the E. aedis and coinfection treatments converged. Some of the proteins differentially abundant in response to infection were identified. They included two vacuolar ATPases, proteins known to have a role in determining the infection success of intracellular parasites. This result suggests microsporidia could influence the infection success of other intracellular pathogens infecting vector species of mosquito, including viruses, Plasmodium and Wolbachia.     

Field trials of various models of the pyramid trap on Glossina palpalis in the Congo

Preliminary trials of 12 models of the pyramid trap were carried out in the Congo on Glossina palpalis palpalis (Robineau-Desvoidy) using Latin square designs. The models were compared with the standard trap with which they differed either in the shape of the pyramid, the addition of a royal blue cloth skirt, or the pattern of the blue-black screen. A decrease in height and/or volume of the pyramid significantly reduced the capture rate. The standard tetrahedral pyramid was significantly superior to both the regular tetrahedral and the trihedral pyramid. The addition of a royal blue cotton skirt modified both the attractiveness and effectiveness of the trap. However, although the attractiveness was probably increased, the skirt may have deterred the flies from entering the pyramid; the best results were obtained with the largest openings. The modification of the blue-black screen pattern may be a way to increase the attraction of flies to the trap. Although no model was found to be significantly superior to the standard, certain gave interesting results which should be investigated further.

---

Résumé Des essais de 12 variants du piège pyramidal ont été réalisés au Congo selon le protocole expérimental des carrés latins, sur Glossina palpalis palpalis (Rob.-Desv.). Les variants ont tous été comparés au modèle standard dont ils diffèrent soit par la forme de la pyramide, soit par l'adjonction d'une juppe de tissu bleu, soit par la recombinaison des parties bleues et noires des écrans. Les résultats ont montré le rôle particulier de ces différents composants du piège au niveau de l'attraction et de l'efficacité à la capture. Les modifications de la hauteur et du volume de la pyramide ont diminué significativement l'efficacité du système de capture, soit en rendant plus difficile l'accès de ce système au tsétsé, soit en leur facilitant la sortie de la pyramide. L'addition d'une jupe de tissu bleu modifie ces deux aspects à la fois, mais, si elle augmente probablement l'attractivité, la jupe de certains modèles gène la pénétration des mouches à l'intérieur de la pyramide. Le réagencement de la couleur bleue et noire des écrans pourrait accroître l'attraction de la mouche ou favoriser son ascension. Bien qu'aucun modèle ne soit apparu significativement supérieur au standard, certains de ceux-ci ont donné des résultats intéressants. Ces modifications constituent donc des voies à explorer, notamment en confrontant ces modèles avec d'autres espèces de tsétsé et dans d'autres environements.