No abstract

High-fat diet (HFD) during lactation alters milk composition and is associated with development of metabolic diseases in the offspring. We hypothesized that HFD affects milk microRNA (miRNA) and mRNA content, which potentially impact offspring development. Our objective was to determine the effect of maternal HFD on secreted milk transcriptome. To meet this objective, 4 wk old female ICR mice were divided into two treatments: control diet containing 10% kcal fat and HFD containing 60% kcal fat. After 4 wk on CD or HFD, mice were bred while continuously fed the same diets. On postnatal day 2 (P2), litters were normalized to 10 pups, and half the pups in each litter were cross-fostered between treatments. Milk was collected from dams on P10 and P12. Total RNA was isolated from milk fat fraction of P10 samples and used for mRNA-Seq and small RNA-Seq. P12 milk was used to determine macronutrient composition. After 4 wk of prepregnancy feeding HFD mice weighed significantly more than did the control mice. Lactose and fat concentration were significantly ( P < 0.05) higher in milk of HFD dams. Pup weight was significantly greater ( P < 0.05) in groups suckled by HFD vs. control dams. There were 25 miRNA and over 1,500 mRNA differentially expressed (DE) in milk of HFD vs. control dams. DE mRNA and target genes of DE miRNA enriched categories that were primarily related to multicellular organismal development. Maternal HFD impacts mRNA and miRNA content of milk, if bioactive nucleic acids are absorbed by neonate differences may affect development.

No abstract

A b s t r a c tWe investigate the feasibility of using instruction compression at some level in a multi-level memory hierarchy to increase memory system performance. For example, compressing at main memory means that main memory and the file system would contain compressed instructions, but upstream caches would see normal uncompressed instructions. Compression effectively increases the memory size and the block size reducing the miss rate at the expense of increased access latency due to decompression delays. We present a simple compression scheme using the most frequently used symbols and evaluate it with several other compression schemes. On a SPARC processor, our scheme obtained compression rirtio of 150% for most programs.We analytically evaluate the impact of compression on the average memory access (ime for various memory systems and compression approaches. Our results show that feasibility of using compression is sensitive to the miss rates and miss penalties at the point of compression and to a lesser extent the amount of compression possible. For high performance workstations of today, compression already shows promise; as miss penalties increase in future, compression will only become more feasible.

Immunometabolic reprogramming due to CD73-produced adenosine is a recognized immunosuppressive mechanism contributing to immune evasion in solid tumors. Adenosine is not only known to contribute to tumor progression, but it has specific roles in driving dysfunction of immune cells, including natural killer (NK) cells. Here, we engineered NK cells to directly target the CD73-adenosine axis by blocking the enzymatic activity of CD73. In doing so, the engineered NK cells not only impaired adenosinergic metabolism driven by the hypoxic uptake of ATP by cancer cells, but also mediated killing of tumor cells due to the specific recognition of overexpressed CD73. This results in a "single agent" immunotherapy that combines antibody specificity, blockade of purinergic signaling, and killing of targets mediated by NK cells. We also showed that CD73-targeted NK cells are potent in vivo and result in tumor arrest, while promoting NK cell infiltration into CD73+ tumors and enhanced intratumoral activation.