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Abstract: Antisocial behavior is a product of multiple interacting sociohereditary variables, yet there is increasing evidence that metal exposure, particularly, manganese and lead, play a role in its epigenesis. Other metals, such as arsenic, cadmium, chromium, and mercury, and exposure to traffic-related air pollution, such as fine particulate matter (≤2.5μm) have been associated with neurological deficits, yet largely unexplored with respect to their relationship with delinquent behavior. The purpose of this study is to evaluate the ecological relationship between county-wide reported airborne emissions of air metals, particulate matter, and youth adjudicated for criminal activity. Metal exposure data were collected from the Environmental Protection Agency AirData. Population statistics were obtained from the United States Census 2000 and adjudication data was obtained from the Courts of Common Pleases from each Ohio County. Simple correlations were calculated with the percentage of adjudications, all covariates, and estimated metal air emissions. Separate negative binomial regression models for each pollutant were used to provide an estimated risk ratio of pollutant emissions on the risk of adjudication for all Ohio counties adjusting for urban–rural residence, percentage of African Americans, median family income, percentage of family below poverty, percentage of high school graduation in 25 years and older populations, and population density. Metal emissions and PM in 1999 were all correlated with adjudication rate (2003–2005 average). Metal emissions were associated with slightly higher risk of adjudication, with about 3–4% increased risk per natural log unit of metal emission except chromium. The associations achieved statistical significance for manganese and mercury. The particulate matter ≤2.5 and ≤10μm emissions had a higher risk estimate, with 12% and 19% increase per natural log unit emission, respectively, and also achieved statistical significance. In summary, airborne exposure to manganese, mercury, and particulate matter are associated with increased risk of adjudication. Causality cannot be proven in observational studies such as this one, but the association warrants further examination in other research studies. Comprehensive epidemiologic investigations of metal exposure in pediatric populations should include social health outcomes, including measures of delinquent or criminal activity. Furthermore, the influence of metals on the neurotoxic pathway leading to delinquent activity should be further explored. [Copyright &y& Elsevier]

Abstract: We present a combination of database screening, synthesis and in vitro testing to identify novel histone acetyltransferase (HAT) inhibitors. The National Cancer Institute compound collection (NCI) and several commercial databases were filtered by similarity-based virtual screening to find new HAT inhibitors. Employing the recombinant HAT p300/CBP-associated factor (PCAF) and two different histone substrates for screening, pyridoisothiazolones were identified as inhibitors of human PCAF. Due to the limited solubility of the initial hits, we synthesized and tested them on PCAF. The compounds inhibit the proliferation of cancer cells. In summary, valuable chemical tools and potential lead candidates for new anticancer agents directed against HATs as new targets have been identified. [Copyright &y& Elsevier]

Histone deactylase inhibitors have emerged as a promising epigenetic therapy for neoplasic indications. The US Food and Drug Administration granted approval to romidepsin for treatment of cutaneous T cell lymphoma (CTCL) in 2009. Phase I/II trials of romidepsin as monotherapy or hybird therapy have demonstrated substantial efficacy profoundly in CTCL and peripheral T-cell lymphoma and marginally in other hematogological malignancies and solid tumors, with a tolerable safety and toxicity profile. The current status of the clinical evaluation of romidepsin is detailed in the present contribution. [ABSTRACT FROM AUTHOR]

The approval of suberoylanilide hydroxamic acid by the FDA for the treatment of cutaneous T-cell lymphoma in October, 2006 sparked a dramatic increase in the development of inhibitors for the class of enzymes known as the histone deacetylases (HDACs). In recent years, a large number of combination therapies involving histone deacetylase inhibitors (HDACIs) have been developed for the treatment of a variety of malignancies and neurodegenerative disorders. Promising evidence has been reported for the treatment of pancreatic cancer, prostate cancer, and leukemia as well as a number of other previously difficult to treat cancers. Drug combination approaches have also shown promise for the treatment of mood disorders including bipolar disorder and depression. In addition to these drug combination approaches, HDACIs alone have demonstrated effectiveness in the treatment of Parkinson''s disease, Alzheimer''s disease, Rubinstein–Taybi syndrome, Rett syndrome, Friedreich''s ataxia, Huntington''s disease, multiple sclerosis, anxiety, and schizophrenia. Adverse inflammatory affects observed with traumatic brain injury and arthritis have also been alleviated by treatment with certain HDACIs. Based on the diverse utility and wide range of mechanistic actions observed with this class of drugs, the future development of better drug combination therapies and more selective HDACIs is warranted. [Copyright &y& Elsevier]

The article presents an interview with Randy L. Jirtle, a professor of radiation oncology at Duke University in Durham, North Carolina, about his career. The interview begins with the selection of Jirtle as the recipient of the Epigenetic Medicine Award in 2008. Jirtle then recalls the individuals who have had an impact on his career path. He also talks about research being conducted in epigenomics.

Presents a historical background on the discussion of epigenetics at the 2004 Cold Spring Harbor Symposia on Quantitative Biology in the U.S. Return to the examination of eukaryotic chromosomes; Propagation of a chromatin mark; Modifications of histone.

Provides information on a study about an epigenetic hypothesis for human brain laterality, handedness and psychosis development that was presented at the 69th Cold Spring Harbor Symposia on Quantitative Biology in the U.S. in 2004. Correlation of brain laterality with hand-use preference; Etiology of handedness; Background on strand-specific imprinting and segregation model for the laterality and the development.

Focuses on a study which deals with the composition of prions of yeast that was presented at the 69th Cold Spring Harbor Symposia on Quantitative Biology in the U.S. in 2004. Information on epigenetics and prions; Constitution of a prion domain in the amino terminus of nonchromosomal genes 2p (Ure2p); Architecture of amyloid filament that was formed from Ure2p.

Highlights a study on the implications of the new field of epigenomics for cancer and other common disease research that was presented at the 69th Cold Spring Harbor Symposia on Quantitative Biology in the U.S. in 2004. Information on the epigenomic approach to cancer; Background on the epigenetics of hereditary disorders; Common disease genetic and epigenetic hypothesis.

Provides information on a study about the epigenetic regulation in the control of flowering (FLC) that was presented at the 69th Cold Spring Harbor Symposia on Quantitative Biology in the U.S. in 2004. Significance of FLC in the vernalization process; Use of an FLC translational fusion for the selection of mutants in FLC regulation; Histone modifications that are associated with epigenetic silencing of FLC.

Focuses on a study on RNA interference and epigenetic control of heterochromatin assembly in fission yeast that was presented at the 69th Cold Spring Harbor Symposia on Quantitative Biology in the U.S. in 2004. Factors of heterochromatin assembly factors in fission yeast; Information on histone code and heterochromatin assembly; Propagation and inheritance of heterochromatin structures.

Focuses on a study about polycomb silencing mechanisms in Drosophila that was presented at the 69th Cold Spring Harbor Symposia on Quantitative Biology in the U.S. in 2004. Maintenance of the epigenetic state; Assembly of polycomb group (PcG) gene proteins in two complexes; Conservation of pre sequences across Drosophila species; Information on the targeting of PcG complexes by DNA-binding domain fusions.

Presents information on a study about the involvement of histone modifications in epigenetic regulation that was presented at the 69th Cold Spring Harbor Symposia on Quantitative Biology in the U.S. in 2004. Types of terminally differentiated cells in gametogenesis; Diagram of cell differentiation based on epigenetic mechanisms; Fundamental roles of histones in orchestrating the epigenetic information.

Presents information on the origin of epigenetics that was presented at the 69th Cold Spring Harbor Symposia on Quantitative Biology in the U.S. in 2004. Definition of epigenetics for molecular biologists; Similarities between epigenetics and epigenesis; Background on epigenetics according to several researchers.

The article discusses epigenetics which is the study of heritable traits that are not reliant on DNA sequence changes. According to the author, epigenetics was known to cell biologists long before it became a popular scientific field as a result of the discovery of mechanisms, such as DNA methylation, that did not change DNA sequences but affected subsequent generations of cells. Topics include how the human genome project sparked an interest in epigenetics, three ways that DNA-inherited messages are altered in organisms, such as small RNA modification of gene expression, and the creation of kits, reagents, and equipment for epigenetic assays. Also discussed are technological innovations for studying DNA methylation including bisulfite treatment and chromatin immunoprecipitation (ChIP).

The article discusses researches which explore the role of epigenetics in determining a baby's weight. Scientists at two U.S. Department of Agriculture (USDA) Agricultural Research Service (ARS) are examining whether the mother's overweight status during pregnancy could affect the child's ability to regulate his or her weight. The research suggests that a baby is more susceptible to become obese if he or she was exposed to the mother's obesity while in the womb.

Highlights a study on a possible epigenetic mechanism for the persistence of memory that was presented at the 69th Cold Spring Harbor Symposia on Quantitative Biology in the U.S. in 2004. Information on synaptic plasticity; Significance of cytoplasmic polyadenylation element binding (CPEB) protein to synaptic protein synthesis; Conformational states of CPEB.

The article focuses on the U.S. National Institutes of Health's (NIH) Roadmap Epigenomics Project and its first data release. It claims that the data include more than 300 maps of epigenetic changes in 56 cell and tissue types that represent a substantial step towards the full epigenome. It adds that the project aims to identify and map human epigenome that would be useful to disease research, fund work on specific diseases and develop novel technologies.

Head and neck squamous cell carcinomas (HNSCCs) represent clinically and etiologically heterogeneous tumors affecting >40 000 patients per year in the USA. Previous research has identified individual epigenetic alterations and, in some cases, the relationship of these alterations with carcinogen exposure or patient outcomes, suggesting that specific exposures give rise to specific types of molecular alterations in HNSCCs. Here, we describe how different etiologic factors are reflected in the molecular character and clinical outcome of these tumors. In a case series of primary, incident HNSCC (n = 68), we examined the DNA methylation profile of 1413 autosomal CpG loci in 773 genes, in relation to exposures and etiologic factors. The overall pattern of epigenetic alteration could significantly distinguish tumor from normal head and neck epithelial tissues (P P < 0.01), we did not observe an association between these profiles and overall patient survival after adjustment for stage; although methylation of a number of specific loci falling in different cellular pathways was associated with overall patient survival. We found that the etiologic heterogeneity of HNSCC is reflected in specific patterns of molecular epigenetic alterations within the tumors and that the DNA methylation profiles may hold clinical promise worthy of further study. [ABSTRACT FROM AUTHOR]

This article discusses research being done on epigenomics of human and mouse tumors. It references two separate studies published in "Cancer Prevention Research" and "Genes, Chromosomes, Cancer" in 2008. Scientists at the University of Southern California revealed the long-term effects of an epigenetic drug in mice. The second study compared methylation profiles in mouse and human mammary tumor cell lines.

The article focuses on the issues concerning the multi-million-dollar project to explore epigenomics in the U.S. It states that the National Institutes of Health (NIH) has already handed out the first payments of the project, but some researchers are outcrying concerns regarding the scientific and economic justification of the program. According to researcher Kevin Struhl of Harvard Medical School in Boston, Massachusetts, the scientists think that the project is a humongous waste of money. He notes that scientific community stresses that focusing on this type of gene modification overlooks key processes such as the work of transcription factors as well as other deoxyribonucleic acid (DNA)-binding proteins.

The article focuses on the two five-year programs of biological research which includes epigenetics and the microbes of bodies host. Epigenetics will catalog genetic changes that affect gene expression but do not involve a change in DNA sequence. The Human Microbiome Project will examine the body's microbial communities and their relation to disease. These programs will be the second round of research initiatives that cut across all 27 institutes and centers at the U.S. National Institutes of Health.