KRAS (G12D) cooperates with AML1/ETO to initiate a mouse model mimicking human acute myeloid leukemia.

BACKGROUND/AIMS: It has been demonstrated that KRAS mutations represent about 90% of cancer-associated mutations, and that KRAS mutations play an essential role in neoplastic transformation. Cancer-associated RAS mutations occur frequently in acute myeloid leukemia (AML), suggesting a functional role for Ras in leukemogenesis. METHODS: We successfully established a mouse model of human leukemia by transplanting bone marrow cells co-transfected with the K-ras (G12D) mutation and AML1/ETO fusion protein. RESULTS: Mice transplanted with AML/ETO+KRAS co-transduced cells had the highest mortality rate than mice transplanted with AML/ETO- or KRAS-transduced cells (115d vs. 150d). Upon reaching a terminal disease stage, EGFP-positive cells dominated their spleen, lymph nodes, peripheral blood and central nervous system tissue. Immunophenotyping, cytologic analyses revealed that AML/ETO+KRAS leukemias predominantly contained immature myeloid precursors (EGFP(+)/c-Kit(+)/Mac-1(-)/Gr-1(-)). Histologic analyses revealed that massive leukemic infiltrations were closely packed in dense sheets that effaced the normal architecture of spleen and thymus in mice transplanted with AML1/ETO + KRAS co-transduced cells. K-ras mRNA and protein expression were upregulated in bone marrow cells of the K-ras group and AML1/ETO + Kras group. The phosphorylation of MEK/ERK was significantly enhanced in the AML1/ETO + Kras group. The similar results of the AML1/ETO + Nras group were consistent with those reported previously. CONCLUSION: Co-transduction of Kras(G12D) and AML1/ETO induces acute monoblastic leukemia. Since expression of mutant K-ras alone was insufficient to induce leukemia, this model may be useful for investigating the multi-step leukemogenesis model of human leukemia.

Coevolutionary insights between promoters and transcription factors in the plant and animal kingdoms.

The divergence and continuous evolution of plants and animals contribute to ecological diversity. Promoters and transcription factors (TFs) are key determinants of gene regulation and transcription throughout life. However, the evolutionary trajectories and relationships of promoters and TFs are still poorly understood. Here, we conducted extensive analysis of large-scale multi-omics sequences in 420 animal species and 223 plant species spanning nearly a billion years of evolutionary history. Results showed that promoter GC-content and TF isoelectric points, as features/signatures that accompany long biological evolution, exhibited increasing growth in animal cells but a decreasing trend in plant cells. Furthermore, the evolutionary trajectories of promoter and TF signatures in the animal kingdom provided further evidence that Mammalia as well as Aves evolved directly from the ancestor Reptilia. The strong correlation between promoter and TF signatures indicates that promoters and TFs formed antagonistic coevolution in the animal kingdom, but mutualistic coevolution in the plant kingdom. The distinct coevolutionary patterns potentially drive the plant-animal divergence，divergent evolution and ecological diversity.

Post-thawing metabolite profile and amino acid oxidation of thawed pork tenderloin by HVEF-A short communication.

The post-thawing quality, metabolite profile and amino acid oxidation of frozen pork tenderloin following the use of a high-voltage electrostatic field (HVEF) were investigated in this study. There were not significant differences of pH for pork thawed by air and HVEF, which were consistent with the lactic acid level and glycogen content. No changes in the tenderness of thawed pork were found. There were only 6 volatiles with different contents in the pork tenderloin (P < 0.05). Moreover, there were no oxidized cysteine and methionine residues in myosin of thawed pork by HVEF. A total of 23 discriminating metabolites between the air-thawed and HVEF-thawed pork after orthogonal partial least squares-discriminate analysis (OPLS-DA). There were 10 pathways containing >5 discriminating metabolites, among them, there were 10 discriminating metabolites in the glycerophospholipid metabolism (ssc00564) and retrograde endocannabinoid signaling (ssc04723). The glycerophospholipid metabolism could be related to the pork spoilage processes.

Effect of electrical stimulation and hot boning on the eating quality of Gannan yak longissimus lumborum.

The objective of this study was to evaluate the effects of electrical stimulation (ES) versus non-electrical stimulation (NES) and type of boning (hot versus cold) on the eating quality of Gannan yak longissimus lumborum. Eighteen Gannan yak bulls were randomly divided into two groups: ES and NES. Hot boning (HB) and cold boning (CB) were applied to the left and right side of the carcasses, respectively. All of the four treatments missed the "ideal" pH/temperature window. HB reduced the rate of pH decline, decreased meat tenderness and water holding capacity. ES increased the rate of pH decline and improved yak meat tenderness (P<0.05); however, ES explained only 1% of the variation in WBSF. HB and ES had no significant effects on cooking loss, L* or b* values of yak meat. Postmortem aging increased yak meat tenderness and improved meat color parameters. HB had negative effects on yak meat quality, while ES could not reverse these deleterious effects.

Development of near infrared reflectance spectroscopy to predict chemical composition with a wide range of variability in beef.

A total of 182 beef samples were minced and divided into calibration set (n=140) and independent validation set (n=42). Calibration models of NIRS (1000-1800nm) were built using partial least squares regression (PLSR) on the calibration set of samples. Both the coefficient of determination in calibration (R(2)C) and the coefficient of determination in prediction (R(2)P) were over 0.98 for all chemical compositions. The ratio performance deviation (RPD) was 17.37, 5.12 and 10.43 for fat, protein and moisture, respectively. The results of the present study indicate the outstanding ability of NIRS to predict chemical composition in beef.

Patient assessment of chronic illness care, glycemic control and the utilization of community health care among the patients with type 2 diabetes in Shanghai, China.

OBJECTIVES: To evaluate the relationship between Patient Assessment of Chronic Illness Care in community health centers and self-management behaviors and glycemic control and to examine the relationship between Patient Assessment of Chronic Illness Care in community health centers and the utilization of community health centers for monitoring and treating diabetes among the patients with type 2 diabetes. METHODS: A questionnaire including self-management behaviors, glycemic control, Patient Assessment of Chronic Illness Care in community health centers and the most often utilized medical institutions for monitoring and treating diabetes (community health centers vs. hospitals) was administered to 960 patients with type 2 diabetes in Shanghai, China. The relationships between Patient Assessment of Chronic Illness Care and self-management behaviors, self-management behaviors and glycemic control, Patient Assessment of Chronic Illness Care and glycemic control, Patient Assessment of Chronic Illness Care and the most often utilized medical institutions for monitoring and treating diabetes were examined. RESULTS: Wilcoxon rank sum tests showed that the high scores of total Patient Assessment of Chronic Illness Care and five subscales in community health centers were positively related to almost all the proper self-management behaviors and good glycemic control (p<0.05). Almost all of the proper self-management behaviors were positively related to good glycemic control (p<0.01). High summary score of the Patient Assessment of Chronic Illness Care was positively associated with the utilization of community health centers for monitoring and treating diabetes (p<0.001). CONCLUSIONS: Patient Assessment of Chronic Illness Care (implementation of the Chronic Care Model) in community health centers was associated with patients' self-management behaviors and glycemic control, and finally was associated with the utilization of community health centers for monitoring and treating diabetes.