Antibody response to Candida albicans cell wall antigens

The cell wall of Candida albicans is not only the structure where many essential biological functions reside but is also a significant source of candidal antigens. The major cell wall components that elicit a response from the host immune system are proteins and glycoproteins, the latter being predominantly mannoproteins. Both carbohydrate and protein moieties are able to trigger immune responses. Proteins and glycoproteins exposed at the most external layers of the wall structure are involved in several types of interactions of fungal cells with the exocellular environment. Thus, coating of fungal cells with host antibodies has the potential to profoundly influence the host-parasite interaction by affecting antibody-mediated functions such as opsonin-enhanced phagocytosis and blocking the binding activity of fungal adhesins to host ligands. In this review we examine various members of the protein and glycoprotein fraction of the C. albicans cell wall that elicit an antibody response in vivo. Some of the studies demonstrate that certain cell wall antigens and anti-cell wall antibodies may be the basis for developing specific and sensitive serologic tests for the diagnosis of candidiasis, particularly the disseminated form. In addition, recent studies have focused on the potential of antibodies against the cell wall protein determinants in protecting the host against infection. Hence, a better understanding of the humoral response triggered by the cell wall antigens of C. albicans may provide the basis for the development of (i) effective procedures for the serodiagnosis of disseminated candidiasis, and (ii) novel prophylactic (vaccination) and therapeutic strategies to control this type of infections.     

Altered expression of Alzheimer's disease-related genes in the cerebellum of autistic patients: a model for disrupted brain connectome and therapy

Autism and Alzheimer''s disease (AD) are, respectively, neurodevelopmental and degenerative diseases with an increasing epidemiological burden. The AD-associated amyloid-β precursor protein-α has been shown to be elevated in severe autism, leading to the ‘anabolic hypothesis'' of its etiology. Here we performed a focused microarray analysis of genes belonging to NOTCH and WNT signaling cascades, as well as genes related to AD and apoptosis pathways in cerebellar samples from autistic individuals, to provide further evidence for pathological relevance of these cascades for autism. By using the limma package from R and false discovery rate, we demonstrated that 31% (116 out of 374) of the genes belonging to these pathways displayed significant changes in expression (corrected P-values <0.05), with mitochondria-related genes being the most downregulated. We also found upregulation of GRIN1, the channel-forming subunit of NMDA glutamate receptors, and MAP3K1, known activator of the JNK and ERK pathways with anti-apoptotic effect. Expression of PSEN2 (presinilin 2) and APBB1 (or F65) were significantly lower when compared with control samples. Based on these results, we propose a model of NMDA glutamate receptor-mediated ERK activation of α-secretase activity and mitochondrial adaptation to apoptosis that may explain the early brain overgrowth and disruption of synaptic plasticity and connectome in autism. Finally, systems pharmacology analyses of the model that integrates all these genes together (NOWADA) highlighted magnesium (Mg²⁺) and rapamycin as most efficient drugs to target this network model in silico. Their potential therapeutic application, in the context of autism, is therefore discussed.     

Description of the female of Evandromyia rupicola (Martins, Godoy & Silva) with a review of the rupicola series (Diptera: Psychodidae: Phlebotominae)

The rupicola series was proposed initially for Evandromyia rupicola (Martins et al) and Evandromyia correalimai (Martins et al), and recently extended with the inclusion of Evandromyia gaucha Andrade-Filho et al and Evandromyia grimaldii Andrade-Filho et al. The female of E. rupicola is here described and illustrated for the first time and its male is redescribed and drawn on the basis of specimens captured in forest on the coast of the state of S?o Paulo, Brazil. The head and genitalia of both sexes of E. correalimai are also illustrated. The distinctive traits among females of the four species and of males of E. rupicola, E. correalimai and E. grimaldii, and the distribution range of these species are commented.     

Regulation of Salmonella-induced neutrophil transmigration by epithelial ADP-ribosylation factor 6

Salmonella typhimurium elicits an acute inflammatory response in the host intestinal epithelium, characterized by the movement of polymorphonuclear leukocytes (PMN) across the epithelial monolayer to the intestinal lumen. It was recently shown that SipA, a protein secreted by S. typhimurium, is necessary and sufficient to drive PMN transmigration across model intestinal epithelia (Lee, C. A., Silva, M., Siber, A. M., Kelly, A. J., Galyov, E., and McCormick, B. A. (2000) Proc. Natl. Acad Sci. USA 97, 12283-12288). However, the epithelial factors responsible for this process have not been identified. Here, for the first time, we demonstrate that S. typhimurium-induced PMN transmigration across Madin-Darby canine kidney-polarized monolayers is regulated by the GTPase ARF6. Apically added S. typhimurium promoted the translocation of ARF6 and its exchange factor ARNO to the apical surface. Overexpression of a dominant-negative mutant of ARF6 inhibited Salmonella-induced PMN transmigration, which was due to a reduction in apical release of the PMN chemoattractant PEEC (pathogen-elicited epithelial chemoattractant), without affecting bacterial internalization. Furthermore, ARF6 and its effector phospholipase D (PLD) were both required for bacteria-induced translocation of protein kinase C (PKC) to membranes. These results describe a novel signal transduction pathway, in which Salmonella initiates an ARF6- and PLD-dependent lipid signaling cascade that, in turn, directs activation of PKC, release of PEEC, and subsequent transepithelial PMN movement.     

Separation of chitosomes and secretory vesicles from the “slime” variant of Neurospora crassa

Cells from the slime variant of Neurospora crassa were broken in isotonic conditions by use of triethanolamine buffer plus EDTA. After removal of large membranous structures by low-speed centrifugation, chitosomes and secretory vesicles were separated by means of gel filtration, precipitation of membranous contaminants with Concanavalin A, and centrifugation in sucrose or glycerol gradients. Polypeptidic composition of fractions enriched in secretory vesicles or chitosomes was found to be distinct. By these criteria we concluded that chitosomes and secretory vesicles represent different populations of microvesicles. Both microvesicular populations appeared free of endoplasmic reticulum and vacuolar contaminants as demonstrated by determination of appropriate enzymatic markers.Abbreviations ER Endoplasmic reticulum - UDP-GlcNAc uridine-5-diphosphate N-acetyl glucosamine - GlcNAc N-acetyl glucosamine - SDS sodium dodecyl sulfate - PMSF phenyl methyl sulfonyl fluoride - EDTA ethylene diamino tetraacetic acid Investigador Nacional de Mexico. On leave from the Centro de Investigacion y Estudios Avanzados (IPN), and the Universidad de Guanajuato, Gto., Mexico     

ATP stimulates inositol phosphates accumulation and calcium mobilization in a primary culture of rat aortic myocytes

The effects of extracellular ATP on phosphoinositide metabolism and intracellular Ca2+ concentration were studied in a primary culture of rat aortic myocytes. ATP increases the level of inositol phosphates, the putative second messenger for Ca2+ mobilization. No saturation of inositol phosphates accumulation is obtained (up to 10(-2) M ATP). Under the same conditions, ATP rapidly mobilizes intracellular Ca2+ in fura-2 loaded myocytes. The mobilization of intracellular Ca2+ is dose-dependent (maximal at 10(-4) M ATP), and is not affected by addition of EGTA. It is concluded that the receptors mediating the cytosolic increase of Ca2+ are of the P2-purinoceptor subtype. The physiological functions of these receptors are not presently known.     

The differential expression of ribosomal 18S RNA paralog genes from the chaetognath <Emphasis Type="Italic">Spadella cephaloptera</Emphasis>

Chaetognaths constitute a small marine phylum of approximately 120 species. Two classes of both 18S and 28S rRNA gene sequences have been evidenced in this phylum, even though significant intraindividual variation in the sequences of rRNA genes is unusual in animal genomes. These observations led to the hypothesis that this unusual genetic characteristic could play one or more physiological role(s). Using in situ hybridization on the frontal sections of the chaetognath Spadella cephaloptera, we found that the 18S Class I genes are expressed in the whole body, with a strong expression throughout the gut epithelium, whereas the expression of the 18S Class II genes is restricted to the oocytes. Our results could suggest that the paralog products of the 18S Class I genes are probably the "housekeeping" 18S rRNAs, whereas those of class II would only be essential in specific tissues. These results provide support for the idea that each type of 18S paralog is important for specific cellular functions and is under the control of selective factors.     

Parasites of Columba livia (Aves: Columbiformes) in Tenerife (Canary Islands) and their role in the conservation biology of the laurel pigeons

The prevalence and intensity of the parasites from 50 wild doves (Columba livia) from the city of Santa Cruz de Tenerife, in the island of Tenerife (Canary Archipelago), were studied. The following ectoparasites were found in apparently healthy pigeons (prevalences are shown in percentage (%) and mean intensities with their standard deviations): the acari Dermanyssus gallinae (De Geer, 1778) (6, 241.0 +/- 138.9) and Tinaminyssus melloi Fain, 1962 (10%, 218.3 +/- 117.3); the louses, Columbicola columbae Linnaeus, 1758 (100%, 111.4 +/- 76.8) and Campanulotes bidentatus Scopoli, 1763 (94%, 48.4 +/- 26.6); and the pigeon fly, Pseudolynchia canariensis Macquart, 1839 (36%, 6.2 +/- 1.6). The endoparasites we found were: a haemoprotozoan species, Haemoproteus columbae Kruze, 1890 (82%, 14.8 +/- 10.3 per 1000); coccidian oocysts, Eimeria sp. (50%, 0.2 x 10(3) +/- 1.7 x 10(3) per gr); a cestode species Raillietina micracantha (Fuhrmann, 1909) López Neyra, 1947 (44%, 12.3 +/- 9.4); and four nematode species, Tetrameres (Tetrameres) fissispina (Diesing, 1861) Travassos, 1915 (4%, 99.5 +/- 34.1), Synhimantus (Dispharynx) spiralis (Molin, 1858) (8%, 46.8 +/- 11.6), Ascaridia columbae (Gmelin, 1790) Travassos, 1913 (40%, 8.4 +/- 8.8) and Aonchotheca sp. (18%, 6.0 +/- 3.1). Several species detected in our study can be pathogens for C. bollii and C. junoniae, which are endemic pigeons of the Canary Islands, considered endangered species. Parasites (ectoparasites, protozoa and helminths) of C. livia found in Tenerife and others from wild and farm birds in the island were considered as healthy controls.     

Association of tracheal placodes with leg primordia in Drosophila and implications for the origin of insect tracheal systems

Adaptation to diverse habitats has prompted the development of distinct organs in different animals to better exploit their living conditions. This is the case for the respiratory organs of arthropods, ranging from tracheae in terrestrial insects to gills in aquatic crustaceans. Although Drosophila tracheal development has been studied extensively, the origin of the tracheal system has been a long-standing mystery. Here, we show that tracheal placodes and leg primordia arise from a common pool of cells in Drosophila, with differences in their fate controlled by the activation state of the wingless signalling pathway. We have also been able to elucidate early events that trigger leg specification and to show that cryptic appendage primordia are associated with the tracheal placodes even in abdominal segments. The association between tracheal and appendage primordia in Drosophila is reminiscent of the association between gills and appendages in crustaceans. This similarity is strengthened by the finding that homologues of tracheal inducer genes are specifically expressed in the gills of crustaceans. We conclude that crustacean gills and insect tracheae share a number of features that raise the possibility of an evolutionary relationship between these structures. We propose an evolutionary scenario that accommodates the available data.