Larvicidal, ovicidal and pupicidal activities of Gliricidia sepium (Jacq.) (Leguminosae) against the malarial vector, Anopheles stephensi Liston (Culicidae: Diptera)

AbstractObjectiveTo investigate the potentiality of mosquitocidal activity of Gliricidia sepium (G. sepium) (Jacq.) (Leguminosae).MethodsTwenty five early third instar larvae of Anopheles stephensi (An. stephensi) were exposed to various concentrations (50-250 ppm) and the 24 h LC50 values of the G. sepium extract was determined by probit analysis. The ovicidal activity was determined against An. stephensi to various concentrations ranging from 25-100 ppm under laboratory conditions. The eggs hatchability was assessed 48 h post treatment. The pupicidal activity was determined against An. stephensi to various concentrations ranging from 25-100 ppm. Mortality of each pupa was recorded after 24 h of exposure to the extract.ResultsResults pertaining to the experiment clearly revealed that ethanol extract showed significant larvicidal, ovicidal and pupicidal activity against the An. stephensi. Larvicidal activity of ethanol extracts of G. sepium showed maximum mortality in 250 ppm concentration (96.0±2.4)%. Furthermore, the LC50 was found to be 121.79 and the LC90 value was recorded to be 231.98 ppm. Ovicidal activity of ethanol extract was assessed by assessing the egg hatchability. Highest concentration of both solvent extracts exhibited 100% ovicidal activity. Similarly, pupae exposed to different concentrations of ethanol extract were found dead with 58.10% adult emergence when it was treated with 25 ppm concentration. Similarly, 18.36 (n=30; 61.20%); 21.28(70.93) and 27.33(91.10) pupal mortality was recorded from the experimental pupae treated with 50, 75 and 100 ppm concentration of extracts. Three fractions have been tested for their larvicidal activity of which the Fraction 3 showed the LC50 and LC90 values of 23.23 and 40.39 ppm. With regard to the ovicidal effect fraction 3 showed highest ovicidal activities than the other two fractions. Furthermore, there were no hatchability was recorded above 50 ppm (100% egg mortality) in the experimental group. Statistically significant pupicidal activity was recorded from 75 ppm concentration.ConclusionsFrom the results it can be concluded the crude extract of G. sepium is an excellent potential for controlling An. stephensi mosquito. It is apparent that, fraction 3 possess a novel and active principle which could be responsible for those biological activities

TDR Targets 6: driving drug discovery for human pathogens through intensive chemogenomic data integration

The volume of biological, chemical and functional data deposited in the public domain is growing rapidly, thanks to next generation sequencing and highly-automated screening technologies. These datasets represent invaluable resources for drug discovery, particularly for less studied neglected disease pathogens. To leverage these datasets, smart and intensive data integration is required to guide computational inferences across diverse organisms. The TDR Targets chemogenomics resource integrates genomic data from human pathogens and model organisms along with information on bioactive compounds and their annotated activities. This report highlights the latest updates on the available data and functionality in TDR Targets 6. Based on chemogenomic network models providing links between inhibitors and targets, the database now incorporates network-driven target prioritizations, and novel visualizations of network subgraphs displaying chemical- and target-similarity neighborhoods along with associated target-compound bioactivity links. Available data can be browsed and queried through a new user interface, that allow users to perform prioritizations of protein targets and chemical inhibitors. As such, TDR Targets now facilitates the investigation of drug repurposing against pathogen targets, which can potentially help in identifying candidate targets for bioactive compounds with previously unknown targets.Fil: Urán Landaburu, Héctor Lionel. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Berenstein, Ariel José. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Videla, Santiago. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Maru, Parag. National Chemical Laboratory; India. Academy of Scientific and Innovative Research; IndiaFil: Shanmugam, Dhanasekaran. Academy of Scientific and Innovative Research; India. National Chemical Laboratory; IndiaFil: Chernomoretz, Ariel. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Agüero, Fernan Gonzalo. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentin

A novel multifunctional oligonucleotide microarray for Toxoplasma gondii

<p>Abstract</p> <p>Background</p> <p>Microarrays are invaluable tools for genome interrogation, SNP detection, and expression analysis, among other applications. Such broad capabilities would be of value to many pathogen research communities, although the development and use of genome-scale microarrays is often a costly undertaking. Therefore, effective methods for reducing unnecessary probes while maintaining or expanding functionality would be relevant to many investigators.</p> <p>Results</p> <p>Taking advantage of available genome sequences and annotation for <it>Toxoplasma gondii </it>(a pathogenic parasite responsible for illness in immunocompromised individuals) and <it>Plasmodium falciparum </it>(a related parasite responsible for severe human malaria), we designed a single oligonucleotide microarray capable of supporting a wide range of applications at relatively low cost, including genome-wide expression profiling for <it>Toxoplasma</it>, and single-nucleotide polymorphism (SNP)-based genotyping of both <it>T. gondii </it>and <it>P. falciparum</it>. Expression profiling of the three clonotypic lineages dominating <it>T. gondii </it>populations in North America and Europe provides a first comprehensive view of the parasite transcriptome, revealing that ~49% of all annotated genes are expressed in parasite tachyzoites (the acutely lytic stage responsible for pathogenesis) and 26% of genes are differentially expressed among strains. A novel design utilizing few probes provided high confidence genotyping, used here to resolve recombination points in the clonal progeny of sexual crosses. Recent sequencing of additional <it>T. gondii </it>isolates identifies >620 K new SNPs, including ~11 K that intersect with expression profiling probes, yielding additional markers for genotyping studies, and further validating the utility of a combined expression profiling/genotyping array design. Additional applications facilitating SNP and transcript discovery, alternative statistical methods for quantifying gene expression, etc. are also pursued at pilot scale to inform future array designs.</p> <p>Conclusions</p> <p>In addition to providing an initial global view of the <it>T. gondii </it>transcriptome across major lineages and permitting detailed resolution of recombination points in a historical sexual cross, the multifunctional nature of this array also allowed opportunities to exploit probes for purposes beyond their intended use, enhancing analyses. This array is in widespread use by the <it>T. gondii </it>research community, and several aspects of the design strategy are likely to be useful for other pathogens.</p

Comparative genomics of the pathogenic ciliate Ichthyophthirius multifiliis, its free-living relatives and a host species provide insights into adoption of a parasitic lifestyle and prospects for disease control

BACKGROUND: Ichthyophthirius multifiliis, commonly known as Ich, is a highly pathogenic ciliate responsible for 'white spot', a disease causing significant economic losses to the global aquaculture industry. Options for disease control are extremely limited, and Ich's obligate parasitic lifestyle makes experimental studies challenging. Unlike most well-studied protozoan parasites, Ich belongs to a phylum composed primarily of free-living members. Indeed, it is closely related to the model organism Tetrahymena thermophila. Genomic studies represent a promising strategy to reduce the impact of this disease and to understand the evolutionary transition to parasitism. RESULTS: We report the sequencing, assembly and annotation of the Ich macronuclear genome. Compared with its free-living relative T. thermophila, the Ich genome is reduced approximately two-fold in length and gene density and three-fold in gene content. We analyzed in detail several gene classes with diverse functions in behavior, cellular function and host immunogenicity, including protein kinases, membrane transporters, proteases, surface antigens and cytoskeletal components and regulators. We also mapped by orthology Ich's metabolic pathways in comparison with other ciliates and a potential host organism, the zebrafish Danio rerio. CONCLUSIONS: Knowledge of the complete protein-coding and metabolic potential of Ich opens avenues for rational testing of therapeutic drugs that target functions essential to this parasite but not to its fish hosts. Also, a catalog of surface protein-encoding genes will facilitate development of more effective vaccines. The potential to use T. thermophila as a surrogate model offers promise toward controlling 'white spot' disease and understanding the adaptation to a parasitic lifestyle

Comparative Genomics of the Apicomplexan Parasites Toxoplasma gondii and Neospora caninum: Coccidia Differing in Host Range and Transmission Strategy

Toxoplasma gondii is a zoonotic protozoan parasite which infects nearly one third of the human population and is found in an extraordinary range of vertebrate hosts. Its epidemiology depends heavily on horizontal transmission, especially between rodents and its definitive host, the cat. Neospora caninum is a recently discovered close relative of Toxoplasma, whose definitive host is the dog. Both species are tissue-dwelling Coccidia and members of the phylum Apicomplexa; they share many common features, but Neospora neither infects humans nor shares the same wide host range as Toxoplasma, rather it shows a striking preference for highly efficient vertical transmission in cattle. These species therefore provide a remarkable opportunity to investigate mechanisms of host restriction, transmission strategies, virulence and zoonotic potential. We sequenced the genome of N. caninum and transcriptomes of the invasive stage of both species, undertaking an extensive comparative genomics and transcriptomics analysis. We estimate that these organisms diverged from their common ancestor around 28 million years ago and find that both genomes and gene expression are remarkably conserved. However, in N. caninum we identified an unexpected expansion of surface antigen gene families and the divergence of secreted virulence factors, including rhoptry kinases. Specifically we show that the rhoptry kinase ROP18 is pseudogenised in N. caninum and that, as a possible consequence, Neospora is unable to phosphorylate host immunity-related GTPases, as Toxoplasma does. This defense strategy is thought to be key to virulence in Toxoplasma. We conclude that the ecological niches occupied by these species are influenced by a relatively small number of gene products which operate at the host-parasite interface and that the dominance of vertical transmission in N. caninum may be associated with the evolution of reduced virulence in this species

Correction: Brugia malayi Asparaginyl-tRNA Synthetase Stimulates Endothelial Cell Proliferation, Vasodilation and Angiogenesis.

[This corrects the article DOI: 10.1371/journal.pone.0146132.]

Brugia malayi Asparaginyl-tRNA Synthetase Stimulates Endothelial Cell Proliferation, Vasodilation and Angiogenesis.

A hallmark of chronic infection with lymphatic filarial parasites is the development of lymphatic disease which often results in permanent vasodilation and lymphedema, but all of the mechanisms by which filarial parasites induce pathology are not known. Prior work showed that the asparaginyl-tRNA synthetase (BmAsnRS) of Brugia malayi, an etiological agent of lymphatic filariasis, acts as a physiocrine that binds specifically to interleukin-8 (IL-8) chemokine receptors. Endothelial cells are one of the many cell types that express IL-8 receptors. IL-8 also has been reported previously to induce angiogenesis and vasodilation, however, the effect of BmAsnRS on endothelial cells has not been reported. Therefore, we tested the hypothesis that BmAsnRS might produce physiological changes in endothelial by studying the in vitro effects of BmAsnRS using a human umbilical vein cell line EA.hy926 and six different endothelial cell assays. Our results demonstrated that BmAsnRS produces consistent and statistically significant effects on endothelial cells that are identical to the effects of VEGF, vascular endothelial growth factor. This study supports the idea that new drugs or immunotherapies that counteract the adverse effects of parasite-derived physiocrines may prevent or ameliorate the vascular pathology observed in patients with lymphatic filariasis

A Hybrid Cross Layer with Harris-Hawk-Optimization-Based Efficient Routing for Wireless Sensor Networks

Efficient clustering and routing is a main challenge in a wireless sensor network (WSN). To achieve better quality-of-service (QoS) performance, this work introduces k-medoids with improved artificial-bee-colony (K-IABC)-based energy-efficient clustering and the cross-layer-based Harris-hawks-optimization-algorithm (CL-HHO) routing protocol for WSN. To overcome the power-asymmetry problem in wireless sensor networks, a cross-layer-based optimal-routing solution is proposed. The goal of cross-layer routing algorithms is to decrease network-transmission delay and power consumption. This algorithm which was used to evaluate and select the effective path route and data transfer was implemented using MATLAB, and the results were compared to some existing techniques. The proposed CL-HHO performs well in packet-loss ratio (PLR), throughput, end-to-end delay (E2E), jitter, network lifetime (NLT) and buffer occupancy. These results are then validated by comparing them to traditional routing strategies such as hierarchical energy-efficient data gathering (HEED), energy-efficient-clustering routing protocol (EECRP), Grey wolf optimization (GWO), and cross-layer-based Ant-Lion optimization (CL-ALO). Compared to the HEED, EECRP, GWO, and CL-ALO algorithms, the proposed CL-HHO outperforms them