48 research outputs found
Inventaire des Plantes MellifÚres du Sud Ouest Algérien
Afin de reconnaĂźtre les principales espĂšces de plantes mellifĂšres spĂ©cifiques au sud ouest algĂ©rien, nous avons effectuĂ© des enquĂȘtes de terrain au cours de la saison 2007-2008, au niveau des rĂ©gions suivantes : Naama et Bechar. Cette Ă©tude nous a permis de mettre en Ă©vidence lâexistence dâune flore diversifiĂ©e, composĂ©e de plantes cultivĂ©es (cultures maraĂźchĂšres et fourragĂšres ; arbres fruitiers et forestiers ; palmier dattier âŠ) mais surtout dâespĂšces spontanĂ©es vivaces et Ă©phĂ©mĂšres. Nous avons recensĂ© 66 espĂšces mellifĂšres dans les rĂ©gions Ă©tudiĂ©es en faisant apparaĂźtre leur pĂ©riode de floraison, les produits rĂ©coltĂ©s par lâabeille.Mots clĂ©s : EspĂšces mellifĂšres â Sud ouest algĂ©rien - Flore spontanĂ©e
Seasonal variation of the diet of the Fennec fox, Vulpes zerda (Canidae, Carnivora), in Algeria
Les variations saisonniĂšres du rĂ©gime alimentaire du Fennec, Vulpes zerda, ont Ă©tĂ© Ă©tudiĂ©es Ă partir de crottes collectĂ©es Ă Ben Ahmed, rĂ©gion de GhardaĂŻa (Sahara septentrional algĂ©rien). De lâautomne 2010 au printemps 2011, 130 crottes ont livrĂ© 726 proies animales appartenant Ă 17 ordres, 30 familles et 75 espĂšces. Les proies principales ont Ă©tĂ© les Insectes (554 individus), suivis par les MammifĂšres (142 individus) et les Arachnides (14 individus). Cependant, en biomasse les MammifĂšres ont Ă©tĂ© les proies dominantes (86,5 %) devant les Insectes (10,7 %) et les oiseaux (1,2 %). Un spectre semblable a Ă©tĂ© trouvĂ© au cours des trois saisons Ă©tudiĂ©es, toutefois les frĂ©quences des principaux groupes ont variĂ© significativement. Lâautomne a Ă©tĂ© la saison de plus forte prĂ©dation sur les MammifĂšres, en hiver les IsoptĂšres ont Ă©tĂ© les proies les plus nombreuses, au printemps ce furent les OrthoptĂšres et les Arachnides. La prĂ©dation des ColĂ©optĂšres, Squamates et Oiseaux a Ă©tĂ© stable au fil des saisons. Ces rĂ©sultats confirment que le Fennec est un prĂ©dateur opportuniste.The seasonal diet of the Fennec fox, Vulpes zerda, has been investigated in Ben Ahmed, GhardaĂŻa region (northern Sahara, Algeria) using scat content analysis. In 130 scats collected from autumn 2010 to spring 2011 we identified 726 animal prey items belonging to 17 orders, 30 families and 75 species. The main preys were insects (554 individuals), followed by mammals (142 individuals) and arachnids (14 individuals). However, biomass was dominated by mammals, (86.5 %), followed by insects (10.7 %) and birds (1.2 %). Similar patterns were observed among the seasons, but the frequencies of the main contributing taxa were significantly different. Autumn was the season when mammals were the most consumed; in winter Isoptera were the most numerous preys; in spring Orthoptera and Arachnida were abundantly fed upon, whereas predation of Coleoptera, squamates and birds were similar along the seasons. These results confirm that the fennec fox is an opportunistic predator
T. gondii RP Promoters & Knockdown Reveal Molecular Pathways Associated with Proliferation and Cell-Cycle Arrest
Molecular pathways regulating rapid proliferation and persistence are fundamental for pathogens but are not elucidated fully in Toxoplasma gondii. Promoters of T. gondii ribosomal proteins (RPs) were analyzed by EMSAs and ChIP. One RP promoter domain, known to bind an Apetela 2, bound to nuclear extract proteins. Promoter domains appeared to associate with histone acetyl transferases. To study effects of a RP gene's regulation in T. gondii, mutant parasites (Îrps13) were engineered with integration of tetracycline repressor (TetR) response elements in a critical location in the rps13 promoter and transfection of a yellow fluorescent-tetracycline repressor (YFP-TetR). This permitted conditional knockdown of rps13 expression in a tightly regulated manner. Îrps13 parasites were studied in the presence (+ATc) or absence of anhydrotetracycline (-ATc) in culture. -ATc, transcription of the rps13 gene and expression of RPS13 protein were markedly diminished, with concomitant cessation of parasite replication. Study of Îrps13 expressing Myc-tagged RPL22, -ATc, showed RPL22 diminished but at a slower rate. Quantitation of RNA showed diminution of 18S RNA. Depletion of RPS13 caused arrest of parasites in the G1 cell cycle phase, thereby stopping parasite proliferation. Transcriptional differences ±ATc implicate molecules likely to function in regulation of these processes. In vitro, -ATc, Îrps13 persists for months and the proliferation phenotype can be rescued with ATc. In vivo, however, Îrps13 could only be rescued when ATc was given simultaneously and not at any time after 1 week, even when L-NAME and ATc were administered. Immunization with Îrps13 parasites protects mice completely against subsequent challenge with wildtype clonal Type 1 parasites, and robustly protects mice against wildtype clonal Type 2 parasites. Our results demonstrate that G1 arrest by ribosomal protein depletion is associated with persistence of T. gondii in a model system in vitro and immunization with Îrps13 protects mice against subsequent challenge with wildtype parasites
Potent Tetrahydroquinolone Eliminates Apicomplexan Parasites
Apicomplexan infections cause substantial morbidity and mortality, worldwide. New, improved therapies are needed. Herein, we create a next generation anti-apicomplexan lead compound, JAG21, a tetrahydroquinolone, with increased sp3-character to improve parasite selectivity. Relative to other cytochrome b inhibitors, JAG21 has improved solubility and ADMET properties, without need for pro-drug. JAG21 significantly reduces Toxoplasma gondii tachyzoites and encysted bradyzoites in vitro, and in primary and established chronic murine infections. Moreover, JAG21 treatment leads to 100% survival. Further, JAG21 is efficacious against drug-resistant Plasmodium falciparum in vitro. Causal prophylaxis and radical cure are achieved after P. berghei sporozoite infection with oral administration of a single dose (2.5 mg/kg) or 3 days treatment at reduced dose (0.625 mg/kg/day), eliminating parasitemia, and leading to 100% survival. Enzymatic, binding, and co-crystallography/pharmacophore studies demonstrate selectivity for apicomplexan relative to mammalian enzymes. JAG21 has significant promise as a pre-clinical candidate for prevention, treatment, and cure of toxoplasmosis and malaria
Author Correction: New paradigms for understanding and step changes in treating active and chronic, persistent apicomplexan infections
Correction to: Scientific Reports https://doi.org/10.1038/srep29179, published online 14 July 201
The use of a P. falciparum specific coiled-coil domain to construct a self-assembling protein nanoparticle vaccine to prevent malaria.
The parasitic disease malaria remains a major global public health concern and no truly effective vaccine exists. One approach to the development of a malaria vaccine is to target the asexual blood stage that results in clinical symptoms. Most attempts have failed. New antigens such as P27A and P27 have emerged as potential new vaccine candidates. Multiple studies have demonstrated that antigens are more immunogenic and are better correlated with protection when presented on particulate delivery systems. One such particulate delivery system is the self-assembling protein nanoparticle (SAPN) that relies on coiled-coil domains of proteins to form stable nanoparticles. In the past we have used de novo designed amino acid domains to drive the formation of the coiled-coil scaffolds which present the antigenic epitopes on the particle surface.
Here we use naturally occurring domains found in the tex1 protein to form the coiled-coil scaffolding of the nanoparticle. Thus, by engineering P27A and a new extended form of the coiled-coil domain P27 onto the N and C terminus of the SAPN protein monomer we have developed a particulate delivery system that effectively displays both antigens on a single particle that uses malaria tex1 sequences to form the nanoparticle scaffold. These particles are immunogenic in a murine model and induce immune responses similar to the ones observed in seropositive individuals in malaria endemic regions.
We demonstrate that our P27/P27A-SAPNs induce an immune response akin to the one in seropositive individuals in Burkina Faso. Since P27 is highly conserved among different Plasmodium species, these novel SAPNs may even provide cross-protection between Plasmodium falciparum and Plasmodium vivax the two major human malaria pathogens. As the SAPNs are also easy to manufacture and store they can be delivered to the population in need without complication thus providing a low cost malaria vaccine
Plasmodium falciparum Parasites Are Killed by a Transition State Analogue of Purine Nucleoside Phosphorylase in a Primate Animal Model
Plasmodium falciparum causes most of the one million annual deaths from malaria. Drug resistance is widespread and novel agents against new targets are needed to support combination-therapy approaches promoted by the World Health Organization. Plasmodium species are purine auxotrophs. Blocking purine nucleoside phosphorylase (PNP) kills cultured parasites by purine starvation. DADMe-Immucillin-G (BCX4945) is a transition state analogue of human and Plasmodium PNPs, binding with picomolar affinity. Here, we test BCX4945 in Aotus primates, an animal model for Plasmodium falciparum infections. Oral administration of BCX4945 for seven days results in parasite clearance and recrudescence in otherwise lethal infections of P. falciparum in Aotus monkeys. The molecular action of BCX4945 is demonstrated in crystal structures of human and P. falciparum PNPs. Metabolite analysis demonstrates that PNP blockade inhibits purine salvage and polyamine synthesis in the parasites. The efficacy, oral availability, chemical stability, unique mechanism of action and low toxicity of BCX4945 demonstrate potential for combination therapies with this novel antimalarial agent
From TgO/GABA-AT, GABA, and T-263 Mutant to Conception of Toxoplasma
Toxoplasma gondii causes morbidity, mortality, and disseminates widely via cat sexual stages. Here, we find T. gondii ornithine aminotransferase (OAT) is conserved across phyla. We solve TgO/GABA-AT structures with bound inactivators at 1.55 Ă
and identify an inactivator selective for TgO/GABA-AT over human OAT and GABA-AT. However, abrogating TgO/GABA-AT genetically does not diminish replication, virulence, cyst-formation, or eliminate cat's oocyst shedding. Increased sporozoite/merozoite TgO/GABA-AT expression led to our study of a mutagenized clone with oocyst formation blocked, arresting after forming male and female gametes, with âRosetta stoneâ-like mutations in genes expressed in merozoites. Mutations are similar to those in organisms from plants to mammals, causing defects in conception and zygote formation, affecting merozoite capacitation, pH/ionicity/sodium-GABA concentrations, drawing attention to cyclic AMP/PKA, and genes enhancing energy or substrate formation in TgO/GABA-AT-related-pathways. These candidates potentially influence merozoite's capacity to make gametes that fuse to become zygotes, thereby contaminating environments and causing disease
The use of a P. falciparum specific coiled-coil domain to construct a self-assembling protein nanoparticle vaccine to prevent malaria
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New paradigms for understanding and step changes in treating active and chronic, persistent apicomplexan infections
Toxoplasma gondii, the most common parasitic infection of human brain and eye, persists across lifetimes, can progressively damage sight, and is currently incurable. New, curative medicines are needed urgently. Herein, we develop novel models to facilitate drug development: EGS strain T. gondii forms cysts in vitro that induce oocysts in cats, the gold standard criterion for cysts. These cysts highly express cytochrome b. Using these models, we envisioned, and then created, novel 4-(1H)-quinolone scaffolds that target the cytochrome bcâ complex Qi site, of which, a substituted 5,6,7,8-tetrahydroquinolin-4-one inhibits active infection (ICâ
â, 30ânM) and cysts (ICâ
â, 4âÎŒM) in vitro, and in vivo (25âmg/kg), and drug resistant Plasmodium falciparum (ICâ
â, <30ânM), with clinically relevant synergy. Mutant yeast and co-crystallographic studies demonstrate binding to the bcâ complex Q[subscript]i site. Our results have direct impact on improving outcomes for those with toxoplasmosis, malaria, and ~2 billion persons chronically infected with encysted bradyzoites