E2F7 and E2F8 Play a Critical Role in Regulating Cell Cycle Progression

Biological Sciences Undergraduate Research ForumE2f7 and E2f8 are the most recently discovered members of the E2F family of transcription factors. The conventional knockout of one or the other of these genes in mice results in no observable phenotype. However, the concurrent loss of both genes results in massive apoptosis and dilation of blood vessels in the embryo and abnormal clustering of cells in the placenta, leading to embryonic lethality at day 11.5 (E11.5). This indicated that the E2F7 and E2F8 proteins are functionally redundant and critical for embryonic viability during mid-gestation. Until recently however, the tissues, cellular processes, and molecular pathways regulated by these two proteins remained unknown. Here, we show through use of a conditional knockout system, that the extra-embryonic functions of E2F7 and E2F8 are both necessary and sufficient for embryonic viability at mid-gestation. We have also defined their roles as cell cycle regulators, with their critical function lying at the G1/S transition. Finally, we have determined the molecular role of E2F7/E2F8 by investigating its activitiy as a transcriptional repressor and illuminating its interactions with E2F3a, a critical member of the E2F activator subclass. By defining the molecular functions and cellular roles of these two proteins, we may better understand the critical roles of E2Fs in cell cycle regulation and learn more about their roles in cancer developmentA five-year embargo was granted for this item

Maize Cultivar Performance under Diverse Organic Production Systems

Maize (Zea mays L.) performance can vary widely between different production systems. The need for high-performing hybrids for organic systems with wide adaptation to various macroenvironments is becoming increasingly important. The goal of this study was to characterize inbred lines developed by distinct breeding programs for their combining ability and hybrid yield performance across diverse organic environments. Parent lines were selected from five different breeding programs to give a sample of publically available germplasm with potential for use in organic production systems with expired plant variety protection (Ex-PVP) and current commercial inbreds as benchmarks. A North Carolina Design II mating design was used to produce all possible cross combinations between seven lines designated as males and seven lines designated as females. A significantly positive general combining ability for the female inbred UHF134 suggests that it performs well in hybrid combination. Significant general combining ability was not observed for any male inbred line in this study. Several significantly positive specific combining abilities suggest that nonadditive genetic effects play an important role in determining yield in this germplasm. Further analysis revealed that hybrids containing either an Ex-PVP line or a commercial inbred line were on average superior to hybrids containing only inbreds developed by the cooperators of this study. This demonstrates the utility of testing inbreds from diverse sources when developing hybrids for organic production systems

Isoniazid Preventive Therapy and Risk for Resistant Tuberculosis

Preventive therapy may increase risk for drug resistance

Canonical and Atypical E2Fs Regulate the Mammalian Endocycle

SUMMARY The endocycle is a variant cell cycle consisting of successive DNA synthesis and Gap phases that yield highly polyploid cells. Although essential for metazoan development, relatively little is known about its control or physiologic role in mammals. Using novel lineage-specific cre mice we identified two opposing arms of the E2F program, one driven by canonical transcription activation (E2F1, E2F2 and E2F3) and the other by atypical repression (E2F7 and E2F8), that converge on the regulation of endocycles in vivo. Ablation of canonical activators in the two endocycling tissues of mammals, trophoblast giant cells in the placenta and hepatocytes in the liver, augmented genome ploidy, whereas ablation of atypical repressors diminished ploidy. These two antagonistic arms coordinate the expression of a unique G2/M transcriptional program that is critical for mitosis, karyokinesis and cytokinesis. These results provide in vivo evidence for a direct role of E2F family members in regulating non-traditional cell cycles in mammals

Management of latent Mycobacterium tuberculosis infection:WHO guidelines for low tuberculosis burden countries

ABSTRACT Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing an

Longitudinal, population-based study of racial/ethnic differences in colorectal cancer survival: impact of neighborhood socioeconomic status, treatment and comorbidity

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer, if detected early, has greater than 90% 5-year survival. However, survival has been shown to vary across racial/ethnic groups in the United States, despite the availability of early detection methods.</p> <p>Methods</p> <p>This study evaluated the joint effects of sociodemographic factors, tumor characteristics, census-based socioeconomic status (SES), treatment, and comorbidities on survival after colorectal cancer among and within racial/ethnic groups, using the SEER-Medicare database for patients diagnosed in 1992–1996, and followed through 1999.</p> <p>Results</p> <p>Unadjusted colorectal cancer-specific mortality rates were higher among Blacks and Hispanic males than whites (relative rates (95% confidence intervals) = 1.34 (1.26–1.42) and 1.16 (1.04–1.29), respectively), and lower among Japanese (0.78 (0.70–0.88)). These patterns were evident for all-cause mortality, although the magnitude of the disparity was larger for colorectal cancer mortality. Adjustment for stage accounted for the higher rate among Hispanic males and most of the lower rate among Japanese. Among Blacks, stage and SES accounted for about half of the higher rate relative to Whites, and within stage III colon and stages II/III rectal cancer, SES completely accounted for the small differentials in survival between Blacks and Whites. Comorbidity did not appear to explain the Black-White differentials in colorectal-specific nor all-cause mortality, beyond stage, and treatment (surgery, radiation, chemotherapy) explained a very small proportion of the Black-White difference. The fully-adjusted relative mortality rates comparing Blacks to Whites was 1.14 (1.09–1.20) for all-cause mortality and 1.21 (1.14–1.29) for colorectal cancer specific mortality. The sociodemographic, tumor, and treatment characteristics also had different impacts on mortality within racial/ethnic groups.</p> <p>Conclusion</p> <p>In this comprehensive analysis, race/ethnic-specific models revealed differential effects of covariates on survival after colorectal cancer within each group, suggesting that different strategies may be necessary to improve survival in each group. Among Blacks, half of the differential in survival after colorectal cancer was primarily attributable to stage and SES, but differences in survival between Blacks and Whites remain unexplained with the data available in this comprehensive, population-based, analysis.</p

Maternal High Fat Diet Is Associated with Decreased Plasma n–3 Fatty Acids and Fetal Hepatic Apoptosis in Nonhuman Primates

To begin to understand the contributions of maternal obesity and over-nutrition to human development and the early origins of obesity, we utilized a non-human primate model to investigate the effects of maternal high-fat feeding and obesity on breast milk, maternal and fetal plasma fatty acid composition and fetal hepatic development. While the high-fat diet (HFD) contained equivalent levels of n-3 fatty acids (FA's) and higher levels of n-6 FA's than the control diet (CTR), we found significant decreases in docosahexaenoic acid (DHA) and total n-3 FA's in HFD maternal and fetal plasma. Furthermore, the HFD fetal plasma n-6∶n-3 ratio was elevated and was significantly correlated to the maternal plasma n-6∶n-3 ratio and maternal hyperinsulinemia. Hepatic apoptosis was also increased in the HFD fetal liver. Switching HFD females to a CTR diet during a subsequent pregnancy normalized fetal DHA, n-3 FA's and fetal hepatic apoptosis to CTR levels. Breast milk from HFD dams contained lower levels of eicosopentanoic acid (EPA) and DHA and lower levels of total protein than CTR breast milk. This study links chronic maternal consumption of a HFD with fetal hepatic apoptosis and suggests that a potentially pathological maternal fatty acid milieu is replicated in the developing fetal circulation in the nonhuman primate

Nutrition and cancer: A review of the evidence for an anti-cancer diet

It has been estimated that 30–40 percent of all cancers can be prevented by lifestyle and dietary measures alone. Obesity, nutrient sparse foods such as concentrated sugars and refined flour products that contribute to impaired glucose metabolism (which leads to diabetes), low fiber intake, consumption of red meat, and imbalance of omega 3 and omega 6 fats all contribute to excess cancer risk. Intake of flax seed, especially its lignan fraction, and abundant portions of fruits and vegetables will lower cancer risk. Allium and cruciferous vegetables are especially beneficial, with broccoli sprouts being the densest source of sulforophane. Protective elements in a cancer prevention diet include selenium, folic acid, vitamin B-12, vitamin D, chlorophyll, and antioxidants such as the carotenoids (α-carotene, β-carotene, lycopene, lutein, cryptoxanthin). Ascorbic acid has limited benefits orally, but could be very beneficial intravenously. Supplementary use of oral digestive enzymes and probiotics also has merit as anticancer dietary measures. When a diet is compiled according to the guidelines here it is likely that there would be at least a 60–70 percent decrease in breast, colorectal, and prostate cancers, and even a 40–50 percent decrease in lung cancer, along with similar reductions in cancers at other sites. Such a diet would be conducive to preventing cancer and would favor recovery from cancer as well