Recombinant yeast screen for new inhibitors of human acetyl-CoA carboxylase 2 identifies potential drugs to treat obesity

Acetyl-CoA carboxylase (ACC) is a key enzyme of fatty acid metabolism with multiple isozymes often expressed in different eukaryotic cellular compartments. ACC-made malonyl-CoA serves as a precursor for fatty acids; it also regulates fatty acid oxidation and feeding behavior in animals. ACC provides an important target for new drugs to treat human diseases. We have developed an inexpensive nonradioactive high-throughput screening system to identify new ACC inhibitors. The screen uses yeast gene-replacement strains depending for growth on cloned human ACC1 and ACC2. In “proof of concept” experiments, growth of such strains was inhibited by compounds known to target human ACCs. The screen is sensitive and robust. Medium-size chemical libraries yielded new specific inhibitors of human ACC2. The target of the best of these inhibitors was confirmed with in vitro enzymatic assays. This compound is a new drug chemotype inhibiting human ACC2 with 2.8 μM IC₅₀ and having no effect on human ACC1 at 100 μM.     

Smoking and risk of glioma: a meta-analysis

Objective  

Although causal relationships between smoking and cancer risk have been established for many sites, most studies of brain cancer have not supported an association. However, two recent cohort studies showed increased risks of glioma among smokers. We quantified the association between smoking and glioma through a meta-analysis of the literature.     

A prolyl endopeptidase-inhibiting benzofuran dimer from Polyozellus multiflex.

A new benzofuran dimer, 5,6,5',6'-tetrahydroxy[3,3']bibenzofuranyl-2,2'-dicarboxylic acid dimethyl ester (kynapcin-24), was isolated from Polyozellus multiflex and shown to noncompetitively inhibit prolyl endopeptidase (PEP), with an IC(50) value of 1.14 microM. Kynapcin-24 was less inhibitory to other serine proteases such as chymotrypsin, trypsin, and elastase.     

Influenza (H5N1) viruses in poultry, Russian Federation, 2005-2006

We studied 7 influenza (H5N1) viruses isolated from poultry in western Siberia and the European part of the Russian Federation during July 2005-February 2006. Full genome sequences showed high homology to Qinghai-like influenza (H5N1) viruses. Phylogenetic analysis not only showed a close genetic relationship between the H5N1 strains isolated from poultry and wild migratory waterfowls but also suggested genetic reassortment among the analyzed isolates. Analysis of deduced amino acid sequences of the M2 and neuraminidase proteins showed that all isolates are potentially sensitive to currently available antiviral drugs. Pathogenicity testing showed that all studied viruses were highly pathogenic in chickens; for 3 isolates tested in mice and 2 tested in ferrets, pathogenicity was heterogeneous. Pathogenicity in mammalian models was generally correlated with Lys at residue 627 of polymerase basic protein 2.     

School food practices of prospective teachers

BACKGROUND: Schoolteachers can affect students' eating habits in several ways: through nutrition knowledge, positive role modeling, and avoidance of unhealthy classroom food practices. In this study, the knowledge, attitudes, and eating behaviors of prospective teachers as determinants of intended classroom food practices and the school environment and its potential impact on classroom food practices were examined and explored. METHODS: One hundred and three students (response rate 79%) enrolled in the final year of a bachelor of education program with at least 22 weeks of practice teaching completed a self-administered questionnaire adapted from the Teens Eating for Energy and Nutrition at School teaching staff survey. Indexes related to classroom food practices, school food environment, personal health, fat intake, and nutrition knowledge were constructed and explored quantitatively using linear modeling techniques and contingency table analysis. RESULTS: The majority of respondents reported a high fat intake (65%) and had mid-to-low nutrition knowledge (72%). While most respondents (93%) believed that a healthy school food environment was important, two thirds reported unhealthy classroom food practices. Unhealthy classroom food practices were more likely to be used by those intending to teach at the secondary level, those who held a high personal health belief, and those who demonstrated less support for a healthy school environment. CONCLUSIONS: These findings suggest that knowledge, attitudes, and food behaviors of prospective teachers may be barriers to promoting healthy food habits to their future students. Further, prospective teachers would benefit from policies and programs that support healthy classroom practices and from compulsory nutrition education in the teacher training curriculum.