Detection of levamisole and its metabolites in horses after oral levamisole administration over seven days.

Objective: Levamisole is a regulated substance sometimes administered to racehorses to treat equine protozoal myelitis. Metabolites include compound II, aminorex, and pemoline. Aminorex and pemoline are Horseracing Integrity and Safety Authority-banned substances.

Expression of select mRNA in Thoroughbreds with catastrophic racing injuries.

Background: The ability to identify horses at risk for catastrophic injuries continues to be a pressing issue for the racing industry, especially given recent events in North America.

Objectives: Since most catastrophic injuries occur in areas of existing pathology and this pathology is likely to elicit an inflammatory response, it was hypothesised that analysis of messenger RNA (mRNA) expression would detect significant changes in select genes in horses at risk for a catastrophic injury.

Study Design: Prospective cohort study.

Epigenome comparisons reveal linkage between gene expression and postnatal remodeling of chromatin domain topology.

Substantial evidence has accumulated linking epigenome change to alterations in stem cell function during postnatal development and aging. Yet much remains to be learned about causal relationships, and large gaps remain in our understanding of epigenome-transcriptome interactions. Here we investigate structural features of large histone H3K27me3-enriched regions in human stem cell-like monocytes and their dendritic cell derivatives, where the H3K27me3 modification is considered to demarcate Polycomb (PcG) domains.

Hepatic Pregnancy Suspected at Term and Successful Delivery of a Live Neonate With Placental Attachment to the Right Lobe of the Liver.

Background: Hepatic pregnancy is an exceptionally rare form of extrauterine pregnancy. Only 21 cases have been reported in the English medical literature over the past 60 years, of which only 29% progressed beyond the first trimester.

Case: We present a case of advanced hepatic pregnancy that was diagnosed at term.

DNA methylome and transcriptome sequencing in human ovarian granulosa cells links age-related changes in gene expression to gene body methylation and 3'-end GC density.

Diminished ovarian function occurs early and is a primary cause for age-related decline in female fertility; however, its underlying mechanism remains unclear. This study investigated the roles that genome and epigenome structure play in age-related changes in gene expression and ovarian function, using human ovarian granulosa cells as an experimental system. DNA methylomes were compared between two groups of women with distinct age-related differences in ovarian functions, using both Methylated DNA Capture followed by Next Generation Sequencing (MethylCap-seq) and Reduced Representation Bisulfite Sequencing (RRBS); their transcriptomes were investigated using mRNA-seq.

Global 'bootprinting' reveals the elastic architecture of the yeast TFIIIB-TFIIIC transcription complex in vivo.

TFIIIB and TFIIIC are multi-subunit factors required for transcription by RNA polymerase III. We present a genome-wide high-resolution footprint map of TFIIIB-TFIIIC complexes in Saccharomyces cerevisiae, obtained by paired-end sequencing of micrococcal nuclease-resistant DNA. On tRNA genes, TFIIIB and TFIIIC form stable complexes with the same distinctive occupancy pattern but in mirror image, termed 'bootprints'.

Genome-wide mapping of nucleosomes in yeast using paired-end sequencing.

The DNA of eukaryotic cells is packaged into chromatin by histone proteins, which play a central role in regulating access to genetic information. The nucleosome core is the basic structural unit of chromatin: it is composed of an octamer of the four major core histones (two molecules each of H2A, H2B, H3, and H4), around which are wrapped ∼1.75 negative superhelical turns of DNA, a total of 145-147bp.

Postnatal development- and age-related changes in DNA-methylation patterns in the human genome.

Alterations in DNA methylation have been reported to occur during development and aging; however, much remains to be learned regarding post-natal and age-associated epigenome dynamics, and few if any investigations have compared human methylome patterns on a whole genome basis in cells from newborns and adults. The aim of this study was to reveal genomic regions with distinct structure and sequence characteristics that render them subject to dynamic post-natal developmental remodeling or age-related dysregulation of epigenome structure. DNA samples derived from peripheral blood monocytes and in vitro differentiated dendritic cells were analyzed by methylated DNA Immunoprecipitation (MeDIP) or, for selected loci, bisulfite modification, followed by next generation sequencing.

Activation-induced disruption of nucleosome position clusters on the coding regions of Gcn4-dependent genes extends into neighbouring genes.

We have used paired-end sequencing of yeast nucleosomal DNA to obtain accurate genomic maps of nucleosome positions and occupancies in control cells and cells treated with 3-aminotriazole (3AT), an inducer of the transcriptional activator Gcn4. In control cells, 3AT-inducible genes exhibit a series of distinct nucleosome occupancy peaks. However, the underlying position data reveal that each nucleosome peak actually consists of a cluster of mutually exclusive overlapping positions, usually including a dominant position.

The centromeric nucleosome of budding yeast is perfectly positioned and covers the entire centromere.

The centromeres of budding yeast are ~120 bp in size and contain three functional elements: an AT-rich region flanked by binding sites for Cbf1 and CBF3. A specialized nucleosome containing the H3 variant Cse4 (CenH3) is formed at the centromere. Our genome-wide paired-end sequencing of nucleosomal DNA reveals that the centromeric nucleosome contains a micrococcal nuclease-resistant kernel of 123-135 bp, depending on the centromere, and is therefore significantly shorter than the canonical nucleosome.

Crystal structures of a halophilic archaeal malate synthase from Haloferax volcanii and comparisons with isoforms A and G.

Background: Malate synthase, one of the two enzymes unique to the glyoxylate cycle, is found in all three domains of life, and is crucial to the utilization of two-carbon compounds for net biosynthetic pathways such as gluconeogenesis. In addition to the main isoforms A and G, so named because of their differential expression in E. coli grown on either acetate or glycolate respectively, a third distinct isoform has been identified.

Chemoradiation in advanced vulval carcinoma.

Introduction: Vulval carcinoma is uncommon, affecting approximately 2 per 100,000 women annually. The treatment of choice is radical vulvectomy and inguinal lymph node dissection. Advanced vulval carcinomas involve midline structures (such as clitoris, urethra, or anus) and/or adjacent pelvic organs or bone, and adequate excision may require urinary diversion, colostomy, or pelvic exenteration.

Episodic ataxia associated with EAAT1 mutation C186S affecting glutamate reuptake.

Background: Episodic ataxia (EA) is variably associated with additional neurologic symptoms. At least 4 genes have been implicated. Recently, a mutation in the SLC1A3 gene encoding the glutamate transporter EAAT1 was identified in a patient with severe episodic and progressive ataxia, seizures, alternating hemiplegia, and migraine headache.

Meeting report: risk assessment of tamiflu use under pandemic conditions.

On 3 October 2007, 40 participants with diverse expertise attended the workshop Tamiflu and the Environment: Implications of Use under Pandemic Conditions to assess the potential human health impact and environmental hazards associated with use of Tamiflu during an influenza pandemic. Based on the identification and risk-ranking of knowledge gaps, the consensus was that oseltamivir ethylester-phosphate (OE-P) and oseltamivir carboxylate (OC) were unlikely to pose an ecotoxicologic hazard to freshwater organisms. OC in river water might hasten the generation of OC-resistance in wildfowl, but this possibility seems less likely than the potential disruption that could be posed by OC and other pharmaceuticals to the operation of sewage treatment plants.

Developmental and epigenetic regulation of the human TLR3 gene.

The receptor encoded by the human TLR3 gene recognizes double-strand RNAs (dsRNAs) associated with viral infection. TLR3 expression is strongly activated upon differentiation of monocytes to dendritic cells, and can be further stimulated by the dsRNA analog polyinosine:polycytosine (PI:C). We report evidence for developmental regulation of the TLR3 gene.

Methylmercury in a predatory fish (Cichla spp.) inhabiting the Brazilian Amazon.

This research tested whether limnological conditions, biological characteristics of fish and anthropogenic impacts influenced the assimilation of methylmercury into the muscle of a sedentary piscivorous fish, Cichla spp., from three rivers (Negro, Madeira, Tapajós) and two hydroelectric reservoirs (Balbina, Tucuruí) within the Brazilian Amazon. Methylmercury in this fish ranged from 0.

Complementary roles for histone deacetylases 1, 2, and 3 in differentiation of pluripotent stem cells.

In eukaryotic cells, covalent modifications to core histones contribute to the establishment and maintenance of cellular phenotype via regulation of gene expression. Histone acetyltransferases (HATs) cooperate with histone deacetylases (HDACs) to establish and maintain specific patterns of histone acetylation. HDAC inhibitors can cause pluripotent stem cells to cease proliferating and enter terminal differentiation pathways in culture.

Structure of the antiviral assembly inhibitor CAP-1 complex with the HIV-1 CA protein.

The CA domain of the human immunodeficiency virus type 1 (HIV-1) Gag polyprotein plays critical roles in both the early and late phases of viral replication and is therefore an attractive antiviral target. Compounds with antiviral activity were recently identified that bind to the N-terminal domain of CA (CA N) and inhibit capsid assembly during viral maturation. We have determined the structure of the complex between CA N and the antiviral assembly inhibitor N-(3-chloro-4-methylphenyl)-N'-{2-[({5-[(dimethylamino)-methyl]-2-furyl}-methyl)-sulfanyl]ethyl}-urea) (CAP-1) using a combination of NMR spectroscopy and X-ray crystallography.

Implications for viral capsid assembly from crystal structures of HIV-1 Gag(1-278) and CA(N)(133-278).

Gag, the major structural protein of retroviruses such as HIV-1, comprises a series of domains connected by flexible linkers. These domains drive viral assembly by mediating multiple interactions between adjacent Gag molecules and by binding to viral genomic RNA and host cell membranes. Upon viral budding, Gag is processed by the viral protease to liberate distinct domains as separate proteins.

Pigmented epithelioid melanocytoma: two case reports.

Because of indolent course without mortality, the term "pigmented epithelioid melanocytoma" has been suggested as a replacement for "equine" or "animal-type" melanoma and for the epithelioid blue nevus of the Carney type, from which they are histologically indistinguishable. This report reviews this concept and recounts in detail two of eighteen cases occurring in residents of the Central Coast of California. This paper also contains clinical photographs of pigmented epithelioid melanocytoma, unlike prior reports.

Mapping development-related and age-related chromatin remodeling by a high throughput ChIP-HPLC approach.

Common to numerous differentiation pathways in vertebrate organisms is the regulation of key genes through epigenetic mechanisms. Less well studied is to what extent cells of a given differentiation state, but examined at different points within the life history of an organism, are distinct at the level of the epigenome. A few instances of such variation have been reported, and it would be of considerable value to have at hand a means to characterize additional examples more efficiently.

Semirandom sampling to detect differentiation-related and age-related epigenome remodeling.

With completion of the human genome project, patterns of higher order chromatin structure can be easily related to other features of genome organization. A well-studied aspect of chromatin, histone H4 acetylation, is examined here on the basis of its role in setting competence for gene activation. Three applications of a new hybrid genome sampling-chromatin immunoprecipitation strategy are described.

Human histone deacetylase SIRT2 interacts with the homeobox transcription factor HOXA10.

Histone deacetylases are required for transcriptional repression in eukaryotes. Saccharomyces cerevisiae has several histone deacetylases, of which ySir2p is the most conserved throughout evolution. Currently, there is no report on the interacting protein partner of a human Sir2 homolog, SIRT2.

Structural insights into the catalytic mechanism of cyclophilin A.

Cyclophilins constitute a ubiquitous protein family whose functions include protein folding, transport and signaling. They possess both sequence-specific binding and proline cis-trans isomerase activities, as exemplified by the interaction between cyclophilin A (CypA) and the HIV-1 CA protein. Here, we report crystal structures of CypA in complex with HIV-1 CA protein variants that bind preferentially with the substrate proline residue in either the cis or the trans conformation.

Interaction of histone acetylases and deacetylases in vivo.

Having opposing enzymatic activities, histone acetylases (HATs) and deacetylases affect chromatin and regulate transcription. The activities of the two enzymes are thought to be balanced in the cell by an unknown mechanism that may involve their direct interaction. Using fluorescence resonance energy transfer analysis, we demonstrated that the acetylase PCAF and histone deacetylase 1 (HDAC1) are in close spatial proximity in living cells, compatible with their physical interaction.