Crystallization and X-ray diffraction analysis of the RNA primer/promoter-binding domain of influenza A virus RNA-dependent RNA polymerase PB2

The C-terminal domain protein of the PB2 subunit of influenza A virus RNA-dependent RNA polymerase was expressed and crystallized and diffraction data were obtained from the crystals

Effects of Pre-Germinated Brown Rice on Blood Glucose and Lipid Levels in Free-Living Patients with Impaired Fasting Glucose or Type 2 Diabetes

White rice (WR) is made by polishing brown rice (BR) and has lost various nutrients; however, most people prefer it to BR, maybe because of the hardness of BR. Pre-germinated brown rice (PGBR) improves the problem of BR. It is made by soaking BR kernels in water to germinate and becomes softer than BR. In this study we compared the effects of WR and PGBR on blood glucose and lipid concentrations in the impaired fasting glucose (IFG) or type 2 diabetes patients. Six men and 5 women with impaired fasting glucose (IFG) or type 2 diabetes were randomly allocated to 6wk on WR or PGBR diet separated by a 2wk washout interval in a crossover design. Each subject was instructed to consume 3 packs of cooked WR or PGBR (180g/pack) daily in each intervention phase. Blood samples were collected 4 times (in study weeks 0, 6, 8 and 14) for biochemical examination. Blood concentrations of fasting blood glucose, fructosamine, serum total cholesterol and triacylglycerol levels were favorably improved on the PGBR diet (p<0.01), but not on the WR diet. The present results suggest that diets including PGBR may be useful to control bl ood glucose level

Fasting remnant lipoproteins can predict postprandial hyperlipidemia

Abstract Background Hypertriglyceridemia and postprandial hyperlipidemia is thought to play an important role in atherosclerosis, but to select patients at high-risk for cardiovascular diseases is difficult with triglycerides (TG) alone in these patients. Methods To predict postprandial hyperlipidemia without inconvenient test meal loading, we examined lipid concentrations before and after test meal loading and fasting adiponectin, and investigated which of these other than TG were significant during the fasting period in 45 healthy individuals (men: women, 26:19). Results TG, remnant-like particle-cholesterol and -triglyceride (RemL-C, RLP-C, and RLP-TG), and TG/apolipoprotein(apo)B were significantly elevated after loading and fasting values significantly and positively correlated with incremental area under the curve (iAUC) (r=0.80, r=0.79, r=0.63, r=0.58, r=0.54; p Conclusion Fasting triglyceride-rich lipoprotein-related values, especially RemL-C, RLP-C, RLP-TG, and TG/apoB are useful predictors of postprandial hyperlipidemia in young healthy individuals. Although fasting adiponectin concentration correlated with the iAUCs for TG, RemL-C, RLP-C, RLP-TG, and TG/apoB, it was not a significant predictor of postprandial hyperlipidemia in multivariable linear regression analysis.</p

Gas6 derived from cancer-associated fibroblasts promotes migration of Axl-expressing lung cancer cells during chemotherapy

金沢大学医薬保健研究域医学系Alterations to the tumor stromal microenvironment induced by chemotherapy could influence the behavior of cancer cells. In the tumor stromal microenvironment, cancer-associated fibroblasts (CAFs) play an important role. Because the receptor tyrosine kinase Axl and its ligand Gas6 could be involved in promoting non-small cell lung cancer (NSCLC), we investigated the role of Gas6 secreted by CAFs during chemotherapy in NSCLC. In a murine model, we found that Gas6 expression by CAFs was upregulated following cisplatin treatment. Gas6 expression might be influenced by intratumoral hypoperfusion during chemotherapy, and it increased after serum starvation in a human lung CAF line, LCAFhTERT. Gas6 is associated with LCAFhTERT cell growth. Recombinant Gas6 promoted H1299 migration, and conditioned medium (CM) from LCAFhTERT cells activated Axl in H1299 cells and promoted migration. Silencing Gas6 in LCAFhTERT reduced the Axl activation and H1299 cell migration induced by CM from LCAFhTERT. In clinical samples, stromal Gas6 expression increased after chemotherapy. Five-year disease-free survival rates for patients with tumor Axl- and stromal Gas6-positive tumors (n = 37) was significantly worse than for the double negative group (n = 12) (21.9% vs 51.3%, p = 0.04). Based on these findings, it is presumed that Gas6 derived from CAFs promotes migration of Axl-expressing lung cancer cells during chemotherapy and is involved in poor clinical outcome. © 2017 The Author(s)

Hereditary diffuse gastric cancer in a Japanese family with CDH1 mutation three case reports

Abstract Background Germline pathogenic variants in the E-cadherin gene CDH1 cause hereditary diffuse gastric cancer (HDGC), which is an autosomal dominant cancer syndrome, accounting for 1–3% of all gastric cancers. HDGC harboring a CDH 1 variant is extremely rare in Japan. Method In this study we report the clinical courses of three cases with HDGC from a single Japanese family. Results The proband exhibited advanced and metastatic gastric cancer, and was found to have a previously reported heterozygous frameshift variant in CDH1 (NM_004360.3:c.1009_1010del:p.Ser337Phefs*12). Five at-risk relatives underwent presymptomatic molecular testing after careful genetic counseling, and three were molecularly diagnosed as positive for the variant. Esophagogastroduodenoscopy was performed in these relatives revealing abnormal small pale mucosal patches, small ulcerative lesion and no abnormal findings. Moreover, random and targeted biopsies were compatible with pathological diagnosis of HDGC in the three cases, all of which underwent total prophylactic gastrectomy. Conclusion It is critical for the assessment and management of HDGC patients to be actively offered a multidisciplinary and familial-oriented approach. Notably, genetic screening in suspected individuals and familial members is a determining piece for a higher detection rate and the identification of clinical relevant mutations in both low and high-incidence gastric cancer countries

An AsCas12f-based compact genome-editing tool derived by deep mutational scanning and structural analysis

SpCas9 and AsCas12a are widely utilized as genome-editing tools in human cells. However, their relatively large size poses a limitation for delivery by cargo-size-limited adeno-associated virus (AAV) vectors. The type V-F Cas12f from Acidibacillus sulfuroxidans is exceptionally compact (422 amino acids) and has been harnessed as a compact genome-editing tool. Here, we developed an approach, combining deep mutational scanning and structure-informed design, to successfully generate two AsCas12f activity-enhanced (enAsCas12f) variants. Remarkably, the enAsCas12f variants exhibited genome-editing activities in human cells comparable with those of SpCas9 and AsCas12a. The cryoelectron microscopy (cryo-EM) structures revealed that the mutations stabilize the dimer formation and reinforce interactions with nucleic acids to enhance their DNA cleavage activities. Moreover, enAsCas12f packaged with partner genes in an all-in-one AAV vector exhibited efficient knock-in/knock-out activities and transcriptional activation in mice. Taken together, enAsCas12f variants could offer a minimal genome-editing platform for in vivo gene therapy