We have identified 242 Anopheles gambiae genes from 18 gene families implicated in innate immunity and have detected marked diversification relative to Drosophila melanogaster . Immune-related gene families involved in recognition, signal modulation, and effector systems show a marked deficit of orthologs and excessive gene expansions, possibly reflecting selection pressures from different pathogens encountered in these insects' very different life-styles. In contrast, the multifunctional Toll signal transduction pathway is substantially conserved, presumably because of counterselection for developmental stability. Representative expression profiles confirm that sequence diversification is accompanied by specific responses to different immune challenges. Alternative RNA splicing may also contribute to expansion of the immune repertoire.

Iron homeostasis is particularly important in pathogenic bacteria, which need to compete with the host for this essential cofactor. InHelicobacter pylori, a causative agent of several gastric pathologies, iron uptake and storage genes are regulated at the transcriptional level by the ferric uptake regulator Fur. The regulatory circuit of Fur has recently come under focus because of an intimate interlink with a broader regulatory network governing metal homeostasis, acidic response, and virulence. To dissect the Fur regulatory circuit and identify in vivo targets of regulation, we developed a genome-wide location analysis protocol which allowed the identification of 200 genomic loci bound by Fur as well as the investigation of the binding efficiency of the protein to these loci in response to iron. Comparative analysis with transcriptomes of wild-type andfurdeletion mutant strains allowed the distinction between targets associated with Fur regulation and genes indirectly influenced by thefurmutation. The Fur regulon includes 59 genes, 25 of which appear to be positively regulated. A case study conducted by primer extension analysis of two oppositely regulated genes,hpn2andflaB, suggests that negative regulation as well as positive regulation occurs at the transcriptional level. Furthermore, the results revealed the existence of 13 Fur targeted loci within polycistronic operons, which were associated with transcript deregulation in thefurmutant strain. This study provides a systematic insight of Fur regulation at the genome-wide level inH. pyloriand points to regulatory functions extending beyond the classical Fur repression paradigm.

The epidermal growth factor receptor (EGFR) plays a pivotal role in the proliferation and metastatization of cancer cells. Aberrancies in the expression and activation of EGFR are hallmarks of many human malignancies. As such, EGFR-targeted therapies hold significant potential for the cure of cancers. In recent years, photodynamic therapy (PDT) has gained increased interest as a non-invasive cancer treatment. In PDT, a photosensitizer is excited by light to produce reactive oxygen species, resulting in local cytotoxicity. One of the critical aspects of PDT is to selectively transport enough photosensitizers to the tumors environment. Accordingly, an increasing number of strategies have been devised to foster EGFR-targeted PDT. Herein, we review the recent nanobiotechnological advancements that combine the promise of PDT with EGFR-targeted molecular cancer therapy. We recapitulate the chemistry of the sensitizers and their modes of action in PDT, and summarize the advantages and pitfalls of different targeting moieties, highlighting future perspectives for EGFR-targeted photodynamic treatment of cancer.

The genomic locus SRPN10 of the malaria vector Anopheles gambiae codes for four alternatively spliced serine protease inhibitors of the serpin superfamily. The four 40- to 42-kDa isoforms differ only at their C terminus, which bears the reactive site loop, and exhibit protein sequence similarity with other insect serpins and mammalian serpins of the ovalbumin family. Inhibition experiments with recombinant purified SRPN10 serpins reveal distinct and specific inhibitory activity of three isoforms toward different proteases. All isoforms are mainly expressed in the midgut but also in pericardial cells and hemocytes of the mosquito. The cellular localization of SRPN10 serpins is nucleocytoplasmic in pericardial cells, in hemocytes and in a hemocyte-like mosquito cell line, but in the gut the proteins are mostly localized in the nucleus. Although the transcript levels of all SRPN10 isoforms are marginally affected by bacterial challenge, the transcripts of two isoforms (KRAL and RCM) are induced in female mosquitoes in response to midgut invasion by Plasmodium berghei ookinetes. The KRAL and RCM SRPN10 isoforms represent new potential markers to study the ookinete midgut invasion process in anopheline mosquitoes.

Sp22D , a modular serine protease encompassing chitin binding, low density lipoprotein receptor, and scavenger receptor cysteine-rich domains, was identified by molecular cloning in the malaria vector, Anopheles gambiae . It is expressed in multiple body parts and during much of development, most intensely in hemocytes. The protein appears to be posttranslationally modified. Its integral, putatively glycosylated form is secreted in the hemolymph, whereas a smaller form potentially generated by proteolytic processing is associated with the tissues. Bacterial challenge or wounding result in low-level RNA induction, but the protein does not bind to bacteria, nor is its processing affected by infection. However, Sp22D binds to chitin with high affinity and undergoes transient changes in processing during pupal to adult metamorphosis; it may respond to exposure to naked chitin during tissue remodeling or damage.