Application paléoécologique de la méthode d''analyse factorielle en composantes principales: Interprétation des microfaunes de foraminifères planctoniques quaternaires en Méditerranée. III. Les séquences paléoclimatiques. Conclusions générales

The statistical analysis (Q mode) of the microfauna of 135 bottom and core samples from the Mediterranean provides evidence of the predominating local conditions in each of the two basins.

Temperature, which plays a primary role in the distribution of foraminiferal species, only takes second place when one considers the regrouping of the layers.

Once the temperature factor is identified, its variations provide a precise climatic curve with the advantage of not having to make any subjective interpretation of the assemblages.

Résumé

L'analyse en mode Q des microfaunes de 135 échantillons de Méditerrannée (niveaux de surface et carottages) met en évidence la prédominance des conditions locales propres à chacun des deux bassins.

La température, qui joue un rôle primordial dans la répartition des espèces de Foraminifères, n'intervient qu'en second lieu lorsqu'on considère les regroupements des niveaux.

Une fois le facteur thermique identifié, ses variations fournissent une courbe climatique précise qui présente l'avantage de ne nécessiter aucune interprétation subjective des assemblages.     

Trisomy 9p with an isochromosome of 9p

An 18 1/2-year-old female is described with moderately severe mental retardation, the phenotype of the trisomy 9p syndromy, and an isochromosome for the short arm of a chromosome 9, contained in an unique karyotype, 46,XX,-9,t(7q9q),+ iso 9p.     

Caspase-9

Caspase-9 is a member of caspase family of cysteine proteases that have been implicated in apoptosis and cytokine processing. When cells receive apoptotic stimuli, mitochondria releases cytochrome c which then binds to Apaf-1, the mammalian Ced-4 homologue, together with dATP. The resultant complex recruits Caspase-9 leading to its activation. Activated Caspase-9 cleaves downstream caspases such as Caspase-3, -6 and -7 initiating the caspase cascade. The majority of homozygous Caspase-9 null mice die perinatally with a markedly enlarged and malformed cerebrum caused by a reduction of apoptosis during early brain development. Thus, Caspase-9 function is essential for apoptosis during normal development of the central nervous system. These data suggest that inhibition of Caspase-9 activity would render opportunity to treat patients suffering from neurological diseases such as stroke, neurodegenerative diseases or brain injury caused by hypoxia.     

Acétolyse d'une diazocétone derivée d'octose: synthése d'une N-acétyllincosamine protégée, de ses epiméres en c-6 et c-7, et d'une 3-oxétanone á chane latérale glucidique

The acetolysis with anhydrous acetic acid of the diazoketone 1, prepared from potassium 1,2:3,4-di-O-isopropylidene-α-D-galacturonate, gave ketoacetates having the D-glycero (3)and L-glycero (5)configuration at C-7, together with the 3-oxetanone 7, a product of pyranose-ring opening. Starting from the ketoacetates 3 and 5, the lincosamine derivative, 6-acetamido-6,8-dideoxy-1,2:,4-di-O-isopropylidene -α-D-erythro-D-galacto-octopyranose (8), and its three diastereoisomers at C-6 and C-7 (9, 10, and 11) were obtained by oximation, reduction, and N-acetylation.

Résumé

L'acétolyse par l'acide acétique anhydre de la diazocétone 1 dérivée du 1,2:3,4-di-O-isopropylidéne-α-D-galacturonate de potassium, donne les céto-acétates deconfiguration D-glycéro (3) et L-glycéro (5) sur C-7, ainsi que la 3-oxétanone 7 qui résulte de l'ouverture du cycle pyranosique. A partir des céto-acétates 3 et 5, on a obtenu, par oximation, réduction et N-acétylation, le dérivé de la lincosamine, 6-acétamido-6,8-didésoxy-1,2:3,4-di-O-isopropylidéne-α-D-érythro-D-galacto-octo-pyranose (8), et ses trois diastéréoisoméres en C-6 et C-7 (9, 10 et 11).     

Trisomy 9p with i(9p) and t(9q18p)

Summary The trisomy 9p syndrome in a 2-year-old girl with moderate mental retardation is presented. She has a unique karyotype with a de novo isochromosome 9p and a translocation between 9q and 18p.     

Étude ultrastructurale du cycle nucléolaire de Physarum polycephalum après mise en évidence préférentielle des RNP par la réaction régressive à l''EDTA

Nucleolar cycle in Physarum polycephalum was studied using EDTA preferential stain for RNP. We have been able to establish the following.

1. 1. The nucleolar remnants that are observed during mitosis correspond to the fibrillar zones of the interphase nucleolus.

2. 2. In prometaphase and metaphase the nucleolar remnants lie peripherically around the chromosomal mass with which they are only superficially associated.

3. 3. Preribosomal granules appear 10–15 min after metaphase in the prenucleolar bodies.

The results shown that the interphase nucleolus is an assembly of multiple subunits. The relationship between the nucleolar remnants and chromosomes is discussed in the light of the recent understanding of the extrachromosomal nature of rDNA.Le cycle nucléolaire de Physarum polycephalum a été étudié en microscopie électronique après réaction régressive à l'EDTA qui met préférentiellement en évidence les RNP. Nous avons suivi ainsi la dispersion du nucléole en prophase, le devenir des restes nucléolaires au cours de la métaphase et de la télophase, puis l'apparition des corps prénucléolaires en début d'interphase.     

Les groupements mitochondriaux des cellules germinales des poissons téléostéens cyprinidés : II. Étude autoradiographique à haute résolution de l'incorporation de phénylalanine H et d' uridine H

A high resolution autoradiographic study of the incorporation of tritiated uridine and amino acids by the mitochondrial groups, which are typical of most of germ cells at the beginning of gametogenesis, has been made on tench spermatocytes. By this technique, we confirm the partially proteinacious composition of the intermitochondrial “cement”; and for the first time, the presence of RNA in the “cement” is demonstrated by autoradiography. Moreover, a study of the kinetics of the incorporation of both precursors makes likely the hypothesis that at least a part of the “cement” derived from nucleocytoplasmic transfer. Since the biogenesis of mitochondria results from the complementary functioning of the two protein synthesic systems, the cytoplasmic one, which is preponderant, and the mitochondrial one, the mitochondrial groups seem to be the direct visualization of the contribution of the nuclear genome to the edification of new mitochondria.L'étude par autoradiographie à haute résolution de l'incorporation d'uridine et d'acides aminés tritiés par les groupements mitochondriaux, formations caractéristiques de la plupart des cellules germinales en début de gamétogenèse, a été effectuée dans les spermatocytes de tanche. Elle permet de confirmer la nature partiellement protéique du ciment intermitochondrial, et de mettre enévidence, pour la première fois par autoradiographie, la présence d'ARN dans ce ciment . En outre, l'étude cinétique de l'incorporation des deux catégories de précurseurs rend fort vraisemblable l'hypothèse de l'origine d'une partie au moins du ciment par transfert nucléocytoplasmique. La biogenèse des mitochondries résultant du fonctionnement complémentaire de deux systèmes de synthèse protéique, l'un prépondérant, cytoplasmique, l'autre minoritaire, mitochondrial, les groupements mitochondriaux semblent bien être une visualisation directe de la contribution du génome nucléaire à l'édification de mitochondries nouvelles.     

Toll-Like Receptor 9 Alternatively Spliced Isoform Negatively Regulates TLR9 Signaling in Teleost Fish

Toll-like receptor 9 (TLR9) recognizes and binds unmethylated CpG motifs in DNA, which are found in the genomes of bacteria and DNA viruses. In fish, Tlr9 is highly diverse, with the number of introns ranging from 0 to 4. A fish Tlr9 gene containing two introns has been reported to express two alternatively spliced isoforms, namely gTLR9A (full-length) and gTLR9B (with a truncated Cʹ-terminal signal transducing domain), whose regulation and function remain unclear. Here, we report a unique regulatory mechanism of gTLR9 signaling in orange-spotted grouper (Epinephelus coioides), whose gTlr9 sequence also contains two introns. We demonstrated that the grouper gTlr9 gene indeed has the capacity to produce two gTLR9 isoforms via alternative RNA splicing. We found that gTLR9B could function as a negative regulator to suppress gTLR9 signaling as demonstrated by the suppression of downstream gene expression. Following stimulation with CpG oligodeoxynucleotide (ODN), gTLR9A and gTLR9B were observed to translocate into endosomes and co-localize with ODN and the adaptor protein gMyD88. Both gTLR9A and gTLR9B could interact with gMyD88; however, gTLR9B could not interact with downstream IRAK4 and TRAF6. Further analysis of the expression profile of gTlr9A and gTlr9B upon immune-stimulation revealed that the two isoforms were differentially regulated in a time-dependent manner. Overall, these data suggest that fish TLR9B functions as a negative regulator, and that its temporal expression is mediated by alternative RNA splicing. This has not been observed in mammalian TLR9s and might have been acquired relatively recently in the evolution of fish.     

Kinetic mechanism of RGS9-1 potentiation by R9AP

The duration of the photoreceptor's response to a light stimulus determines the speed at which an animal adjusts to ever-changing conditions of the visual environment. One critical component which regulates the photoresponse duration on the molecular level is the complex between the ninth member of the regulators of G protein signaling family (RGS9-1) and its partner, type 5 G protein beta-subunit (Gbeta5L). RGS9-1.Gbeta5L is responsible for the activation of the GTPase activity of the photoreceptor-specific G protein, transducin. Importantly, this function of RGS9-1.Gbeta5L is regulated by its membrane anchor, R9AP, which drastically potentiates the ability of RGS9-1.Gbeta5L to activate transducin GTPase. In this study, we address the kinetic mechanism of R9AP action and find that it consists primarily of a direct increase in the RGS9-1.Gbeta5L activity. We further showed that the binding site for RGS9-1.Gbeta5L is located within the N-terminal putative trihelical domain of R9AP, and even though this domain is sufficient for binding, it takes the entire R9AP molecule to potentiate the activity of RGS9-1.Gbeta5L. The mechanism revealed in this study is different from and complements another well-established mechanism of regulation of RGS9-1.Gbeta5L by the effector enzyme, cGMP phosphodiesterase, which is based entirely on the enhancement in the affinity between RGS9-1.Gbeta5L and transducin. Together, these mechanisms ensure timely transducin inactivation in the course of the photoresponse, a requisite for normal vision.     

Cel9M, a new family 9 cellulase of the Clostridium cellulolyticum cellulosome

A new cellulosomal protein from Clostridium cellulolyticum Cel9M was characterized. The protein contains a catalytic domain belonging to family 9 and a dockerin domain. Cel9M is active on carboxymethyl cellulose, and the hydrolysis of this substrate is accompanied by a decrease in viscosity. Cel9M has a slight, albeit significant, activity on both Avicel and bacterial microcrystalline cellulose, and the main soluble sugar released is cellotetraose. Saccharification of bacterial microcrystalline cellulose by Cel9M in association with two other family 9 enzymes from C. cellulolyticum, namely, Cel9E and Cel9G, was measured, and it was found that Cel9M acts synergistically with Cel9E. Complexation of Cel9M with the mini-CipC1 containing the cellulose binding domain, the X2 domain, and the first cohesin domain of the scaffoldin CipC of the bacterium did not significantly increase the hydrolysis of Avicel and bacterial microcrystalline cellulose.     

Regulation of Bone Morphogenetic Protein 9 (BMP9) by Redox-dependent Proteolysis

BMP9, a member of the TGFβ superfamily, is a homodimer that forms a signaling complex with two type I and two type II receptors. Signaling through high-affinity activin receptor-like kinase 1 (ALK1) in endothelial cells, circulating BMP9 acts as a vascular quiescence factor, maintaining endothelial homeostasis. BMP9 is also the most potent BMP for inducing osteogenic signaling in mesenchymal stem cells in vitro and promoting bone formation in vivo. This activity requires ALK1, the lower affinity type I receptor ALK2, and higher concentrations of BMP9. In adults, BMP9 is constitutively expressed in hepatocytes and secreted into the circulation. Optimum concentrations of BMP9 are essential to maintain the highly specific endothelial-protective function. Factors regulating BMP9 stability and activity remain unknown. Here, we showed by chromatography and a 1.9 Å crystal structure that stable BMP9 dimers could form either with (D-form) or without (M-form) an intermolecular disulfide bond. Although both forms of BMP9 were capable of binding to the prodomain and ALK1, the M-form demonstrated less sustained induction of Smad1/5/8 phosphorylation. The two forms could be converted into each other by changing the redox potential, and this redox switch caused a major alteration in BMP9 stability. The M-form displayed greater susceptibility to redox-dependent cleavage by proteases present in serum. This study provides a mechanism for the regulation of circulating BMP9 concentrations and may provide new rationales for approaches to modify BMP9 levels for therapeutic purposes.     

BDKRB2 GENE -9/+9 POLYMORPHISM AND SWIMMING PERFORMANCE

The aim of the study was to evaluate the association between swimming performance and the -9/+9 (rs5810761) polymorphism within the BDKRB2 gene in successful competitive swimmers. Best individual swimming results expressed in FINA points achieved at short, middle and long distance events of 157 well-trained Polish swimmers were incorporated into an analysis. Athletes’ genotype and allele distributions were analysed in comparison to 230 unrelated sedentary subjects who served as controls with the χ² test. All samples were genotyped for the BDKRB2 -9/+9 polymorphism using the polymerase chain reaction (PCR). The effects of genotype on swimming performance were analysed with two-way (3 x 2; genotype x gender) analysis of variance with metrical age as a covariate for each distance specialization. No statistical differences in the genotype and allele frequencies were found in long distance swimmers when compared with the total group of swimmers or controls. The BDKRB2 +9/-9 genotype had no significant effect on swimming performance at short, middle or long distance, regardless of gender. The results of this study do not support the hypothesis that the BDKRB2 -9/+9 polymorphism is associated with swimming performance in Polish swimmers.     

The transposon Tn9 generates a 9 bp repeated sequence during integration.

We performed a genetic and sequencing analysis of insertions of the transposon Tn9 into the lac operon of E. coli. Genetic mapping of 70 insertions into lacl and Z shows that starting from the same point on the chromosome, Tn9 goes to at least 50 different points in these two genes. Although there are preferred regions for insertion, these consist of multiple integration points within a small area, as demonstrated by pairwise crosses and restriction mapping. Sequence analysis of three Tn9 insertions reveals that Tn9 integration is associated with a direct repeat of 9 base pairs (bp) of host sequence. We show that these extra 9 nucleotide pairs are generated upon insertion and not brought in with the element.