The Search for Putative Hits in Combating Leishmaniasis:The Contributions of Natural Products Over the Last Decade

Despite advancements in the areas of omics and chemoinformatics,potent novel biotherapeutic molecules with new modes of actions are needed for leishmaniasis.The socioeconomic burden of leishmaniasis remains alarming in endemic regions.Currently,reports from existing endemic areas such as Nepal,Iran,Brazil,India,Sudan and Afghanistan,as well as newly affected countries such as Peru,Bolivia and Somalia indicate concerns of chemoresistance to the classical antimonial treatment.As a result,effective antileishmanial agents which are safe and affordable are urgently needed.Natural products from both flora and fauna have contributed immensely to chemotherapeutics and serve as vital sources of new chemical agents.This review focuses on a systematic cross-sectional view of all characterized anti-leishmanial compounds from natural sources over the last decade.Furthermore,IC_(50)/EC_(50),cytotoxicity and suggested mechanisms of action of some of these natural products are provided.The natural product classification includes alkaloids,terpenes,terpenoids,and phenolics.The plethora of reported mechanisms involve calcium channel inhibition,immunomodulation and apoptosis.Making avail-able enriched data pertaining to bioactivity and mechanisms of natural products complement current efforts geared towards unraveling potent leishmanicides of therapeutic relevance.

A Systematic Phenotypic Screen of F-box Genes Through a Tissue-specific RNAi-based Approach in Drosophila

F-box proteins are components of the SCF （SkpA-Cullin 1-F-box） E3 ligase complexes, acting as the specificity-determinants in targeting substrate proteins for ubiquitination and degradation. In humans, at least 22 out of 75 F-box proteins have experimentally documented substrates, whereas in Drosophila 12 F-box proteins have been characterized with known substrates. To systematically investigate the genetic and molecular functions of F-box proteins in Drosophila, we performed a survey of the literature and databases. We identified 45 Drosophila genes that encode proteins containing at least one F-box domain. We collected publically available RNAi lines against these genes and used them in a tissue-specific RNAi-based phenotypic screen. Here, we present our systematic phenotypic dataset from the eye, the wing and the notum. This dataset is the first of its kind and represents a useful resource for future studies of the molecular and genetic functions of F-box genes in Drosophila. Our results show that, as expected, F-box genes in Drosophila have regulatory roles in a diverse array of processes including cell proliferation, cell growth, signal transduction, and cellular and animal survival.

Genome-Wide Identification and Functional Analysis of Genes Expressed Ubiquitously in Rice

Genes that are expressed ubiquitously throughout all developmental stages are thought to be necessary for basic biological or cellular functions. Therefore, determining their biological roles is a great challenge. We identified 4034 of these genes in rice after studying the results of Agilent 44K and Affymetrix meta- anatomical expression profiles. Among 105 genes that were characterized by loss-of-function analysis, 79 were classified as members of gene families, the majority of which were predominantly expressed. Using T-DNA insertional mutants, we examined 43 genes and found that loss of expression of six genes caused developing seedor seedling-defective phenotypes. Of these, three are singletons without similar family members and defective phenotypes are expected from mutations. Phylogenomic analyses integrating genome-wide transcriptome data revealed the functional dominance of three ubiquitously expressed fam- ily genes. Among them, we investigated the function of OsO3g19890, which is involved in ATP generation within the mitochondria during endosperm development. We also created and evaluated functional net- works associated with this gene to understand the molecular mechanism. Our study provides a useful strategy for pheonome analysis of ubiquitously expressed genes in rice.