Novel factors of Anopheles gambiae haemocyte immune response to Plasmodium berghei infection

Background Insect haemocytes mediate cellular immune responses (e.g., phagocytosis) and contribute to the synthesis of humoral immune factors. In previous work, a genome-wide molecular characterization of Anopheles gambiae circulating haemocytes was followed by functional gene characterization using cell-based RNAi screens. Assays were carried out to investigate the role of selected haemocyte-specific or enriched genes in phagocytosis of bacterial bio-particles, expression of the antimicrobial peptide cecropin1, and basal and induced expression of the mosquito complement factor LRIM1 (leucine-rich repeat immune gene I). Findings Here we studied the impact of a subset of genes (37 candidates) from the haemocyte-specific dsRNA collection on the development of Plasmodium in the mosquito by in vivo gene silencing. Our screening identifies 10 novel factors with a role in the mosquito response to Plasmodium. Analysis of in vivo screening phenotypes reveals a significant anti-correlation between the prevalence of oocysts and melanised ookinetes. Conclusions Among novel immune genes are putative pattern recognition proteins (leucine-rich repeat, fibrinogen-domain and R-type lectins), immune modulation and signalling proteins (LPS-induced tumor necrosis factor alpha factor, LITAF and CLIP proteases), and components of extracellular matrix such as laminin and collagen. Additional identified proteins such as the storage protein hexamerin and vesicular-type ATPase (V-ATPase) are associated for the first time with the mosquito response against Plasmodium

MinoanER: Schema-Agnostic, Non-Iterative, Massively Parallel Resolution of Web Entities

Entity Resolution (ER) aims to identify different descriptions in various Knowledge Bases (KBs) that refer to the same entity. ER is challenged by the Variety, Volume and Veracity of entity descriptions published in the Web of Data. To address them, we propose the MinoanER framework that simultaneously fulfills full automation, support of highly heterogeneous entities, and massive parallelization of the ER process. MinoanER leverages a token-based similarity of entities to define a new metric that derives the similarity of neighboring entities from the most important relations, as they are indicated only by statistics. A composite blocking method is employed to capture different sources of matching evidence from the content, neighbors, or names of entities. The search space of candidate pairs for comparison is compactly abstracted by a novel disjunctive blocking graph and processed by a non-iterative, massively parallel matching algorithm that consists of four generic, schema-agnostic matching rules that are quite robust with respect to their internal configuration. We demonstrate that the effectiveness of MinoanER is comparable to existing ER tools over real KBs exhibiting low Variety, but it outperforms them significantly when matching KBs with high Variety.Comment: Presented at EDBT 2001

Massively-Parallel Feature Selection for Big Data

We present the Parallel, Forward-Backward with Pruning (PFBP) algorithm for feature selection (FS) in Big Data settings (high dimensionality and/or sample size). To tackle the challenges of Big Data FS PFBP partitions the data matrix both in terms of rows (samples, training examples) as well as columns (features). By employing the concepts of $p$-values of conditional independence tests and meta-analysis techniques PFBP manages to rely only on computations local to a partition while minimizing communication costs. Then, it employs powerful and safe (asymptotically sound) heuristics to make early, approximate decisions, such as Early Dropping of features from consideration in subsequent iterations, Early Stopping of consideration of features within the same iteration, or Early Return of the winner in each iteration. PFBP provides asymptotic guarantees of optimality for data distributions faithfully representable by a causal network (Bayesian network or maximal ancestral graph). Our empirical analysis confirms a super-linear speedup of the algorithm with increasing sample size, linear scalability with respect to the number of features and processing cores, while dominating other competitive algorithms in its class

The Anopheles Mosquito Microbiota and Their Impact on Pathogen Transmission

International audienc

Sequence-structure-function relations of the mosquito leucine-rich repeat immune proteins.

<p>Abstract</p> <p>Background</p> <p>The discovery and characterisation of factors governing innate immune responses in insects has driven the elucidation of many immune system components in mammals and other organisms. Focusing on the immune system responses of the malaria mosquito, <it>Anopheles gambiae</it>, has uncovered an array of components and mechanisms involved in defence against pathogen infections. Two of these immune factors are LRIM1 and APL1C, which are leucine-rich repeat (LRR) containing proteins that activate complement-like defence responses against malaria parasites. In addition to their LRR domains, these leucine-rich repeat immune (LRIM) proteins share several structural features including signal peptides, patterns of cysteine residues, and coiled-coil domains.</p> <p>Results</p> <p>The identification and characterisation of genes related to <it>LRIM1 </it>and <it>APL1C </it>revealed putatively novel innate immune factors and furthered the understanding of their likely molecular functions. Genomic scans using the shared features of <it>LRIM1 </it>and <it>APL1C </it>identified more than 20 <it>LRIM</it>-like genes exhibiting all or most of their sequence features in each of three disease-vector mosquitoes with sequenced genomes: <it>An. gambiae</it>, <it>Aedes aegypti</it>, and <it>Culex quinquefasciatus</it>. Comparative sequence analyses revealed that this family of mosquito <it>LRIM</it>-like genes is characterised by a variable number of 6 to 14 LRRs of different lengths. The "Long" LRIM subfamily, with 10 or more LRRs, and the "Short" LRIMs, with 6 or 7 LRRs, also share the signal peptide, cysteine residue patterning, and coiled-coil sequence features of LRIM1 and APL1C. The "TM" LRIMs have a predicted C-terminal transmembrane region, and the "Coil-less" LRIMs exhibit the characteristic LRIM sequence signatures but lack the C-terminal coiled-coil domains.</p> <p>Conclusions</p> <p>The evolutionary plasticity of the LRIM LRR domains may provide templates for diverse recognition properties, while their coiled-coil domains could be involved in the formation of LRIM protein complexes or mediate interactions with other immune proteins. The conserved LRIM cysteine residue patterns are likely to be important for structural fold stability and the formation of protein complexes. These sequence-structure-function relations of mosquito LRIMs will serve to guide the experimental elucidation of their molecular roles in mosquito immunity.</p

Large-Scale Modelling of the Environmentally-Driven Population Dynamics of Temperate Aedes albopictus (Skuse)

The Asian tiger mosquito, Aedes albopictus, is a highly invasive vector species. It is a proven vector of dengue and chikungunya viruses, with the potential to host a further 24 arboviruses. It has recently expanded its geographical range, threatening many countries in the Middle East, Mediterranean, Europe and North America. Here, we investigate the theoretical limitations of its range expansion by developing an environmentally-driven mathematical model of its population dynamics. We focus on the temperate strain of Ae. albopictus and compile a comprehensive literature-based database of physiological parameters. As a novel approach, we link its population dynamics to globally-available environmental datasets by performing inference on all parameters. We adopt a Bayesian approach using experimental data as prior knowledge and the surveillance dataset of Emilia-Romagna, Italy, as evidence. The model accounts for temperature, precipitation, human population density and photoperiod as the main environmental drivers, and, in addition, incorporates the mechanism of diapause and a simple breeding site model. The model demonstrates high predictive skill over the reference region and beyond, confirming most of the current reports of vector presence in Europe. One of the main hypotheses derived from the model is the survival of Ae. albopictus populations through harsh winter conditions. The model, constrained by the environmental datasets, requires that either diapausing eggs or adult vectors have increased cold resistance. The model also suggests that temperature and photoperiod control diapause initiation and termination differentially. We demonstrate that it is possible to account for unobserved properties and constraints, such as differences between laboratory and field conditions, to derive reliable inferences on the environmental dependence of Ae. albopictus populations