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Objective: Exosomes (Exos) are membrane-encased vesicles derived by nearly all cell types for intercellular communication and regulation. They also received attention for their use as natural therapeutic platforms and drug delivery system. Classically activated M1 macrophages suppress tumor growth by releasing pro-inflammatory factors. This study investigated the suitability of M1-exosomes (M1-Exos) as drug carrier and their effect on the NF-κB signal pathway and further detected whether macrophages repolarization can potentiate the antitumor activities of chemotherapeutics. Methods: M1-Exos were isolated from M1-macrophages by ultracentrifugation and characterized by transmission electron, nanoparticle tracking analysis, dynamic light scattering and western blot. Then M1-Exos were used as Paclitaxel (PTX) carriers to prepare a nano-formulation (PTX- M1-Exos). A relatively simple slight sonication method was used to prepare the drug delivery system (PTX-M1-Exos). The cytotoxicity of PTX-M1-Exos on cancer cells was detected by MTT and flow cytometry in vitr o. 4T1 tumor bearing mice were used to perform the therapeutic effect of PTX-M1-Exos in vivo . Results: The expression of caspase-3 in breast cancer cells was increased when co-incubated with macrophages in the presence of M1-Exos in vitro . The production of pro-inflammatory cytokines was increased after exposure of macrophages in M1-Exos. M1-Exos provided a pro-inflammatory environment which enhanced the anti-tumor activity via caspase-3 mediated pathway. The treatment of M1-Exos to the tumor bearing mice exhibit anti-tumor effects in vivo . Meanwhile, the treatment of PTX-M1-Exos demonstrated higher anti-tumor effects than the M1-Exos or PTX group. Conclusion: The results in our study indicate that the M1-Exos act as the carrier to deliver PTX into the tumor tissues, and also enhance the anti-tumor effects of chemotherapeutics in tumor bearing mice.

Cayman ataxia is a recessive congenital ataxia restricted to one area of Grand Cayman Island. Comparative mapping suggested that the locus on 19p13.3 associated with Cayman ataxia might be homologous to the locus on mouse chromosome 10 associated with the recessive ataxic mouse mutant jittery. Screening genes in the region of overlap identified mutations in a novel predicted gene in three mouse jittery alleles, including the first mouse mutation caused by an Alu-related (B1 element) insertion. We found two mutations exclusively in all individuals with Cayman ataxia. The gene ATCAY or Atcay encodes a neuron-restricted protein called caytaxin. Caytaxin contains a CRAL-TRIO motif common to proteins that bind small lipophilic molecules. Mutations in another protein containing a CRAL-TRIO domain, alpha-tocopherol transfer protein (TTPA), cause a vitamin E-responsive ataxia. Three-dimensional protein structural modeling predicts that the caytaxin ligand is more polar than vitamin E. Identification of the caytaxin ligand may help develop a therapy for Cayman ataxia.

Phenotypes that might otherwise reveal a gene’s function can be obscured by genes with overlapping function. This phenomenon is best-known within gene families, where an important shared function may only be revealed by mutating all family members. Here we describe the ‘Green Monster’ technology enabling the precise deletion of many genes. In this method, a population of deletion strains with each deletion marked by an inducible green fluorescent protein (GFP) reporter gene, is subjected to repeated rounds of mating, meiosis, and flow-cytometric enrichment. This results in the aggregation of multiple deletion loci within single cells. The Green Monster strategy is potentially applicable to assembling other engineered alterations in any species with sex or alternative means of allelic assortment. To demonstrate the technology, we generated a single broadly drug-sensitive strain of Saccharomyces cerevisiae bearing precise deletions of all 16 adenosine triphosphate-binding cassette transporters within clades associated with multi-drug resistance.