Exemples de tératologie chez les Chitinozoaires du Pridoli de Libye et implications sur la signification biologique du groupe

Jaglin, J.-C. & Paris, F. 1992 04 IS: Exemples de tératologie chez les Chitinozoaires du Pridoli de Libye et implications sur la signification biologique du groupe. [Teratologic cases among Pridolian chitinozoans from Libya and implications on the biological interpretation of the group.] Lethaia , Vol. 25, pp. 151–164. Oslo. ISSN 0024–1164.
Fairly numerous chitinozoans displaying morphological anomalies are recorded in Late Silurian subsurface material from Western Libya. The individuals described and illustrated in our paper range exclusively in a short interval at the top of the investigated sequence. These abnormal vesicles are interpreted as teratologic cases related lo an event of unknown origin. From our conclusions, the hypothesis of vegetative reproduction stages stated by previous authors seems unlikely. Therefore we still interpret the chitinozoan vesicles as eggs (or to a lesser extent as spores) of marine organisms. * Libya, Chitinozoans, Silurian, teratology, chitinozoan affinities .     

Entamoeba dispar: molecular characterization of the galactose/N-acetyl-d-galactosamine lectin

Amebiasis contributes to approximately 50 million cases of life-threatening dysentery worldwide. Comparison of the lectins from Entamoeba histolytica (pathogenic) and Entamoeba dispar (nonpathogenic) was undertaken to elucidate the differential roles of this molecule in invasion versus colonization. Surface lectin was less abundant on axenic E. dispar than on axenic E. histolytica, commensurate with differences in lectin (heavy and light subunits) RNA when assessed by semiquantitative RT-PCR. The 1G7 epitope, which falls within the immunodominant and immunoprotective cysteine-rich region (480-900), was absent on axenic E. dispar. Indirect immunofluorescence, transient transection of COS7, and immunoprecipitation demonstrated that the 1G7 epitope was conserved in the nonpathogenic lectin homologue but not exposed on live E. dispar trophozoites. Hgl2 (E. histolytica) and Dhgl2 (E. dispar) lectin homologues demonstrated comparable high-affinity binding to multivalent GalNAc(19) BSA. These data provide evidence for relative gene and conformational regulation of the E.dispar lectin.     

Immune and endothelial activation markers and risk stratification of childhood pneumonia in Uganda: A secondary analysis of a prospective cohort study

BackgroundDespite the global burden of pneumonia, reliable triage tools to identify children in low-resource settings at risk of severe and fatal respiratory tract infection are lacking. This study assessed the ability of circulating host markers of immune and endothelial activation quantified at presentation, relative to currently used clinical measures of disease severity, to identify children with pneumonia who are at risk of death.Methods and findingsWe conducted a secondary analysis of a prospective cohort study of children aged 2 to 59 months presenting to the Jinja Regional Hospital in Jinja, Uganda between February 2012 and August 2013, who met the Integrated Management of Childhood Illness (IMCI) diagnostic criteria for pneumonia. Circulating plasma markers of immune (IL-6, IL-8, CXCL-10/IP-10, CHI3L1, sTNFR1, and sTREM-1) and endothelial (sVCAM-1, sICAM-1, Angpt-1, Angpt-2, and sFlt-1) activation measured at hospital presentation were compared to lactate, respiratory rate, oxygen saturation, procalcitonin (PCT), and C-reactive protein (CRP) with a primary outcome of predicting 48-hour mortality. Of 805 children with IMCI pneumonia, 616 had severe pneumonia. Compared to 10 other immune and endothelial activation markers, sTREM-1 levels at presentation had the best predictive accuracy in identifying 48-hour mortality for children with pneumonia (AUROC 0.885, 95% CI 0.841 to 0.928; p = 0.03 to p < 0.001) and severe pneumonia (AUROC 0.870, 95% CI 0.824 to 0.916; p = 0.04 to p < 0.001). sTREM-1 was more strongly associated with 48-hour mortality than lactate (AUROC 0.745, 95% CI 0.664 to 0.826; p < 0.001), respiratory rate (AUROC 0.615, 95% CI 0.528 to 0.702; p < 0.001), oxygen saturation (AUROC 0.685, 95% CI 0.594 to 0.776; p = 0.002), PCT (AUROC 0.650, 95% CI 0.566 to 0.734; p < 0.001), and CRP (AUROC 0.562, 95% CI 0.472 to 0.653; p < 0.001) in cases of pneumonia and severe pneumonia. The main limitation of this study was the unavailability of radiographic imaging.ConclusionsIn this cohort of Ugandan children, sTREM-1 measured at hospital presentation was a significantly better indicator of 48-hour mortality risk than other common approaches to risk stratify children with pneumonia. Measuring sTREM-1 at clinical presentation may improve the early triage, management, and outcome of children with pneumonia at risk of death.Trial registrationThe trial was registered at clinicaltrial.gov ({"type":"clinical-trial","attrs":{"text":"NCT 04726826","term_id":"NCT04726826"}}NCT 04726826).

Chloe R. McDonald and colleagues assess the ability of immune and endothelial activation markers to identify risk of death from pneumonia among children in Uganda.     

The Guanine Nucleotide Exchange Factor Tiam1 Affects Neuronal Morphology; Opposing Roles for the Small GTPases Rac and Rho

The invasion-inducing T-lymphoma invasion and metastasis 1 (Tiam1) protein functions as a guanine nucleotide exchange factor (GEF) for the small GTPase Rac1. Differentiation-dependent expression of Tiam1 in the developing brain suggests a role for this GEF and its effector Rac1 in the control of neuronal morphology. Here we show that overexpression of Tiam1 induces cell spreading and affects neurite outgrowth in N1E-115 neuroblastoma cells. These effects are Rac-dependent and strongly promoted by laminin. Overexpression of Tiam1 recruits the α6β1 integrin, a laminin receptor, to specific adhesive contacts at the cell periphery, which are different from focal contacts. Cells overexpressing Tiam1 no longer respond to lysophosphatidic acid– induced neurite retraction and cell rounding, processes mediated by Rho, suggesting that Tiam1-induced activation of Rac antagonizes Rho signaling. This inhibition can be overcome by coexpression of constitutively active RhoA, which may indicate that regulation occurs at the level of Rho or upstream. Conversely, neurite formation induced by Tiam1 or Rac1 is further promoted by inactivating Rho. These results demonstrate that Rac- and Rho-mediated pathways oppose each other during neurite formation and that a balance between these pathways determines neuronal morphology. Furthermore, our data underscore the potential role of Tiam1 as a specific regulator of Rac during neurite formation and illustrate the importance of reciprocal interactions between the cytoskeleton and the extracellular matrix during this process.     

Chromosomal integration and homologous gene targeting by replication-incompetent vectors based on the autonomous parvovirus minute virus of mice

The molecular mechanisms responsible for random integration and gene targeting by recombinant adeno-associated virus (AAV) vectors are largely unknown, and whether vectors derived from autonomous parvoviruses transduce cells by similar pathways has not been investigated. In this report, we constructed vectors based on the autonomous parvovirus minute virus of mice (MVM) that were designed to introduce a neomycin resistance expression cassette (neo) into the X-linked human hypoxanthine phosphoribosyl transferase (HPRT) locus. High-titer, replication-incompetent MVM vector stocks were generated with a two-plasmid transfection system that preserved the wild-type characteristic of packaging only one DNA strand. Vectors with inserts in the forward or reverse orientations packaged noncoding or coding strands, respectively. In human HT-1080 cells, MVM vector random integration frequencies (neo(+) colonies) were comparable to those obtained with AAV vectors, and no difference was observed for noncoding and coding strands. HPRT gene-targeting frequencies (HPRT mutant colonies) were lower with MVM vectors, and the noncoding strand frequency was threefold greater than that of the coding strand. Random integration and gene-targeting events were confirmed by Southern blot analysis of G418- and 6-thioguanine (6TG)-resistant clones. In separate experiments, correction of an alkaline phosphatase (AP) gene by gene targeting was nine times more effective with a coding strand vector. The data suggest that single-stranded parvoviral vector genomes are substrates for gene targeting and possibly for random integration as well.     

Cysteamine, the natural metabolite of pantetheinase, shows specific activity against Plasmodium

In mice, loss of pantetheinase activity causes susceptibility to infection with Plasmodium chabaudi AS. Treatment of mice with the pantetheinase metabolite cysteamine reduces blood-stage replication of P. chabaudi and significantly increases survival. Similarly, a short exposure of Plasmodium to cysteamine ex vivo is sufficient to suppress parasite infectivity in vivo. This effect of cysteamine is specific and not observed with a related thiol (dimercaptosuccinic acid) or with the pantethine precursor of cysteamine. Also, cysteamine does not protect against infection with the parasite Trypanosoma cruzi or the fungal pathogen Candida albicans, suggesting cysteamine acts directly against the parasite and does not modulate host inflammatory response. Cysteamine exposure also blocks replication of P. falciparum in vitro; moreover, these treated parasites show higher levels of intact hemoglobin. This study highlights the in vivo action of cysteamine against Plasmodium and provides further evidence for the involvement of pantetheinase in host response to this infection.     

Photoperiod and temperature as triggers in the seasonality ofDelesseria sanguinea

The red algaDelesseria sanguinea is strongly seasonal, producing gametangia in early tetrasporangia in mid- and new blades in late winter. A lamp was installed in the shallow subtidal off the Isle of Man, illuminating about 40 plants ofDelesseria for one hour in the night or day. Single blades from separate plants were held in laboratory tanks at different temperatures and in short days, long days and with a night-break. In the sea, the night-break prevented fertility in tetrasporophytes but some gametophytes became fertile. New blades were stimulated, arising 6 weeks early. Their lengths indicated a saturation level of about 10 μmol m⁻² s⁻¹ for one hour in 24. Growth rate calculations suggested a delay in stimulation until the ambient sea temperature dropped to 13°C. Tetrasporangia were formed after the night-break ceased in December but not January. In day-addition of light there was slight, if any, stimulation of blade production. In the laboratory, gametogenesis occurred readily in short days but not in long days or with a night-break. There was little or no effect of temperature between 8 and 14°C. Tetraspores were rarely formed in the laboratory. The timing of gametogenesis suggested a critical daylength of about 14 h. New blades were clearly stimulated by lower temperatures in the laboratory, few forming at 14°C and many at 7–10°C. They appeared mainly in long days or with a night-break but formed in short days after gametangia production. It is concluded that both gamete and tetraspore production are under photoperiodic control but require different conditions, possibly gametogenesis needing fewer cycles. There is some evidence for antagonism between new blade and reproductive structure initiation. The critical daylength could involve a timing differential of a month over the species geographical range. On the other hand it is suggested that its southern limit could be determined by the winter isotherm of 13°C, warmer than which might not allow blade initiation.