A Mammalian Cell's Guide on How to Process a Bacteriophage.

Bacteriophages are enigmatic entities that defy definition. Classically, they are specialist viruses that exclusively parasitize bacterial hosts. Yet this definition becomes limiting when we consider their ubiquity in the body coupled with their vast capacity to directly interact with the mammalian host. While phages certainly do not infect nor replicate within mammalian cells, they do interact with and gain unfettered access to the eukaryotic cell structure. With the growing appreciation for the human virome, coupled with our increased application of phages to patients within clinical settings, the potential impact of phage-mammalian interactions is progressively recognized. In this review, we provide a detailed mechanistic overview of how phages interact with the mammalian cell surface, the processes through which said phages are internalized by the cell, and the intracellular processing and fate of the phages. We then summarize the current state-of-the-field with respect to phage-mammalian interactions and their associations with health and disease states.

Follistatin is a novel therapeutic target and biomarker in FLT3/ITD acute myeloid leukemia.

Internal tandem duplication of Fms-like tyrosine kinase 3 (FLT3/ITD) occurs in about 30% of acute myeloid leukemia (AML) and is associated with poor response to conventional treatment and adverse outcome. Here, we reported that human FLT3/ITD expression led to axis duplication and dorsalization in about 50% of zebrafish embryos. The morphologic phenotype was accompanied by ectopic expression of a morphogen follistatin (fst) during early embryonic development. Increase in fst expression also occurred in adult FLT3/ITD-transgenic zebrafish, Flt3/ITD knock-in mice, and human FLT3/ITD AML cells. Overexpression of human FST317 and FST344 isoforms enhanced clonogenicity and leukemia engraftment in xenotransplantation model via RET, IL2RA, and CCL5 upregulation. Specific targeting of FST by shRNA, CRISPR/Cas9, or antisense oligo inhibited leukemic growth in vitro and in vivo. Importantly, serum FST positively correlated with leukemia engraftment in FLT3/ITD AML patient-derived xenograft mice and leukemia blast percentage in primary AML patients. In FLT3/ITD AML patients treated with FLT3 inhibitor quizartinib, serum FST levels correlated with clinical response. These observations supported FST as a novel therapeutic target and biomarker in FLT3/ITD AML.

Potential Uses of Wild Germplasms of Grain Legumes for Crop Improvement.

Challenged by population increase, climatic change, and soil deterioration, crop improvement is always a priority in securing food supplies. Although the production of grain legumes is in general lower than that of cereals, the nutritional value of grain legumes make them important components of food security. Nevertheless, limited by severe genetic bottlenecks during domestication and human selection, grain legumes, like other crops, have suffered from a loss of genetic diversity which is essential for providing genetic materials for crop improvement programs. Illustrated by whole-genome-sequencing, wild relatives of crops adapted to various environments were shown to maintain high genetic diversity. In this review, we focused on nine important grain legumes (soybean, peanut, pea, chickpea, common bean, lentil, cowpea, lupin, and pigeonpea) to discuss the potential uses of their wild relatives as genetic resources for crop breeding and improvement, and summarized the various genetic/genomic approaches adopted for these purposes.