Ppp6c, which encodes the catalytic subunit of phosphoprotein phosphatase 6 (PP6), is conserved among eukaryotes from yeast to humans. In mammalian cells, PP6 targets IκBε for degradation, activates DNA-dependent protein kinase to trigger DNA repair, and is reportedly required for normal mitosis. Recently, Ppp6c mutations were identified as candidate drivers of melanoma and skin cancer. Nonetheless, little is known about the physiological role of Ppp6c. To investigate this function in vivo, we established mice lacking the Ppp6c phosphatase domain by crossing heterozygous mutants. No viable homozygous pups were born, indicative of a lethal mutation. Ppp6c homozygous mutant embryos were identified among blastocysts, which exhibited a normal appearance, but embryos degenerated by E7.5 and showed clear developmental defects at E8.5, suggesting that mutant embryos die after implantation. Accordingly, homozygous blastocysts showed significant growth failure of the inner cell mass (ICM) in in vitro blastocyst culture, and primary Ppp6c exon4-deficient MEFs showed greatly reduced proliferation. These results establish for the first time that the Ppp6c phosphatase domain is indispensable for mouse embryogenesis after implantation.

Accurate, simple, and valuable analytical methods for detection of food contamination are rapidly expanding to evaluate the validity of food product quality because of ethnic considerations and food safety. Herein molecularly imprinted nanogels (MIP-NGs), capable of porcine serum albumin (PSA) recognition, were prepared as artificial molecular recognition elements. The MIP-NGs were immobilized on a quartz crystal microbalance (QCM) sensor for detection of pork contamination in real beef extract samples. The MIP-NGs-based QCM sensor showed high affinity and excellent selectivity toward PSA compared to reference serum albumins from five different animals. The high PSA specificity of MIP-NGs led to the detection of pork contamination with a detection limit of 1% (v/v) in real beef extract samples. We believe the artificial molecular recognition materials prepared by molecular imprinting are a promising candidate for halal food control.

Nanomaterials have a great potential for use in various biorelated applications such as drug delivery systems and in vivo imaging; understanding nanoparticle–cell interactions is an important requisite for these applications. Herein, the nanoparticle–cell interactions, including the cellular uptake mechanism, were investigated in detail using polymer nanogels possessing molecular recognition ability (molecularly imprinted polymer nanogels: MIP-NGs) capable of protein corona regulation via albumin recognition and using refractory cancer cell lines and an immune-related cell line. Albumin recognition in the MIP-NGs further increased the albumin-dependent inhibition of cellular uptake of the nanogels, including uptake by cancer cells and macrophages. Cellular uptake was inhibited more efficiently in MIP-NGs than in the reference nonimprinted polymer nanogels without albumin recognition cavities. In the presence of serum albumin, MIP-NGs did not cause a significant upregulation of inflammatory reactions as measured by cytokine secretion by macrophages. To the best of our knowledge, our study is the first to use molecular recognition of albumin in nanogels to regulate the protein corona and in turn control cellular interactions. Our results provide strong evidence that MIP-NGs could utilize human serum albumin in the formation of a protein corona to avoid immune responses. We hope our results can provide important insights that translate into biomedical applications of nanomaterials.

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In mammals, the small Arf GTPase-activating protein (SMAP) subfamily of Arf GTPase-activating proteins consists of closely related members, SMAP1 and SMAP2. These factors reportedly exert distinct functions in membrane trafficking, as manifested by different phenotypes seen in single knockout mice. The present study investigated whether SMAP proteins interact genetically. We report for the first time that simultaneous loss of SMAP1 and SMAP2 promotes apoptosis in the distal region of E7.5 mouse embryos, likely resulting in embryonic lethality. Thus, at least one SMAP gene, either SMAP1 or SMAP2, is required for proper embryogenesis.