Characterization of the iron-sulfur clusters in the nitrogenase-like reductase CfbC/D required for coenzyme F biosynthesis.

Coenzyme F is a nickel-containing tetrapyrrole, serving as the prosthetic group of methyl-coenzyme M reductase in methanogenic and methanotrophic archaea. During coenzyme F biosynthesis, the tetrapyrrole macrocycle is reduced by the nitrogenase-like CfbC/D system consisting of the reductase component CfbC and the catalytic component CfbD. Both components are homodimeric proteins, each carrying a [4Fe-4S] cluster.

Low potential enzymatic hydride transfer via highly cooperative and inversely functionalized flavin cofactors.

Hydride transfers play a crucial role in a multitude of biological redox reactions and are mediated by flavin, deazaflavin or nicotinamide adenine dinucleotide cofactors at standard redox potentials ranging from 0 to -340 mV. 2-Naphthoyl-CoA reductase, a key enzyme of oxygen-independent bacterial naphthalene degradation, uses a low-potential one-electron donor for the two-electron dearomatization of its substrate below the redox limit of known biological hydride transfer processes at E°' = -493 mV. Here we demonstrate by X-ray structural analyses, QM/MM computational studies, and multiple spectroscopy/activity based titrations that highly cooperative electron transfer (n = 3) from a low-potential one-electron (FAD) to a two-electron (FMN) transferring flavin cofactor is the key to overcome the resonance stabilized aromatic system by hydride transfer in a highly hydrophobic pocket.

Apd1 and Aim32 Are Prototypes of Bishistidinyl-Coordinated Non-Rieske [2Fe-2S] Proteins.

Apd1, a cytosolic yeast protein, and Aim32, its counterpart in the mitochondrial matrix, have a C-terminal thioredoxin-like ferredoxin (TLF) domain and a widely divergent N-terminal domain. These proteins are found in bacteria, plants, fungi, and unicellular pathogenic eukaryotes but not in Metazoa. Our chemogenetic experiments demonstrate that the highly conserved cysteine and histidine residues within the C-X-C-X-H-X-G-G-H motif of the TLF domain of Apd1 and Aim32 proteins are essential for viability of yeast cells upon treatment with the redox mediators gallobenzophenone or pyrogallol, respectively.

A Comparison of Prompting Strategies to Teach Intraverbals to an Adolescent with Down Syndrome.

Ingvarsson and Hollobaugh (2011) investigated tact- or echoic-to-intraverbal transfer of stimulus control to "wh" questions for three preschool-aged boys with autism. The current study was a systematic replication of this study with an adolescent girl with Down syndrome. A multielement design was used to compare the effectiveness and efficiency of picture or echoic prompts presented on an iPad or in vivo to teach "wh" questions.

Tolerance of rising dietary concentrations of esterified propoxylated glycerol (EPG) among human volunteers.

A solid form of esterified propoxylated glycerol (EPG) was administered to 16 healthy male volunteers in butter-like spread and baked goods, resulting in intakes that rose in 30-g increments from 30 to 150 g; each level was administered on a single day, followed by a 2-day washout period. Elevated serum transaminase (ALT and/or AST) and lower HDL cholesterol levels were noted at 60 g and greater, possibly related to changes in the diet (high-carbohydrate and increasingly low-fat), rather than to EPG itself. There was no apparent association between EPG consumption and adverse effects reported.

Article series: Safety of esterified propoxylated glycerol (EPG), a nonabsorbable fat replacer.

This article introduces a series of articles addressing the safety of esterified propoxylated glycerols (EPGs), a family of fat- and oil-like substances that resemble triglycerides in structure and appearance, but have been modified to prevent or limit their digestion when consumed in food. A general summary of the history, composition, metabolism, and safety of EPGs is provided.

Assessment of the effect of esterified propoxylated glycerol (EPG) on the status of fat-soluble vitamins and select water-soluble nutrients following dietary administration to humans for 8 weeks.

This double-blind, randomized, controlled study assessed the effect of esterified propoxylated glycerol (EPG) on fat-soluble vitamins and select nutrients in human subjects. For 8 weeks, 139 healthy volunteers consumed a core diet providing adequate caloric and nutrient intakes. The diet included items (spread, muffins, cookies, and biscuits) providing EPG (10, 25, and 40 g/day) vs.

Genotoxicity testing of esterified propoxylated glycerol (EPG).

Four versions of esterified propoxylated glycerols (EPGs) were evaluated for potential genotoxicity using a range of in vitro and in vivo assays. H-EPG-05 HR/SO 9:1, H-EPG-05 soyate, and H-EPG-14 soyate were non-mutagenic in reverse mutation assays (maximum concentration 1000 μg/plate) using Salmonella typhimurium and Escherichia coli. Heated and unheated H-EPG-05 HR/SO 9:1 and EPG-05 HR/ST 45:55 were likewise non-mutagenic in reverse mutation assays in S.

90-day dietary toxicity study with esterified propoxylated glycerol (EPG) in micropigs.

The subchronic (90-day) toxicity of esterified propoxylated glycerol (EPG) was assessed in micropigs. Animals (5/sex/group) received feed containing 5%, 10%, and 17% EPG, mixed accordingly throughout the study to deliver 1.5, 3, and 5 g/kg bw/day of EPG, respectively.

Developmental toxicity evaluation of esterified propoxylated glycerol (EPG) administered in the diet to New Zealand white rabbits.

The safety of a "core" version of esterified propoxylated glycerols (EPGs) was assessed in a developmental toxicity study in New Zealand white rabbits, Hra:(NZW)SPF. Four groups each of 18 inseminated female rabbits received diets ad libitum containing concentrations of 0%, 2.5%, 5%, and 10% EPG (w/w) with 6% corn oil (w/w).

90-day dietary toxicity study with esterified propoxylated glycerol (EPG) in rats.

The subchronic (90-day) toxicity of a "core" version of EPG was assessed in rats. Crl:CD-1®(ICR)BR rats (70/sex) received diets containing a constant level of 5% EPG (w/w) or adjusted to deliver 0 (control), 0.5, 1, or 2g/kg of body weight/day (g/kg bw/day).

One-generation reproduction study of esterified propoxylated glycerol (EPG) administered in the feed to CD® (Sprague-Dawley) rats.

This one-generation study assessed the potential of esterified propoxylated glycerol (EPG) to affect reproduction and offspring development in rats. Male and female Crl:CD(SD)BR rats (30/sex/group) were exposed to EPG at 0, 0.5, 1, and 2g/kg bw/day or at 5% (w/w) in the diet prior to (13 weeks), during, and after two consecutive matings.

Effects of leptin Arg25Cys on peripheral mononuclear cell counts and antibody response to vaccination in beef cattle.

A single nucleotide polymorphism (SNP) in the leptin gene that results in Arg25Cys has been associated with beef carcass quality and milk composition in dairy cattle. However, leptin (LEP) also plays a role in immune performance and hence it was important to determine whether selection based on this SNP would negatively affect immune cell numbers or antibody production. LEP c.

Associations between immune function in yearling beef cattle and airborne emissions of sulfur dioxide, hydrogen sulfide, and VOCs from oil and natural gas facilities.

Researchers assessed the associations between airborne emissions from oil and gas field facilities and the structure and function of the immune system of yearling beef cattle in 27 herds during spring 2002. They evaluated the immune systems of these animals by enumerating B lymphocytes and T-lymphocyte subtypes (CD4, CD8, gammadelta, and WC1) in peripheral circulation and by measuring systemic antibody production in response to vaccination. Researchers prospectively measured exposure to sulfur dioxide, hydrogen sulfide, and volatile organic compounds (VOCs) by using air-quality data from passive monitors installed in pastures and wintering areas.

Associations between in utero exposure to airborne emissions from oil and gas production and processing facilities and immune system outcomes in neonatal beef calves.

To determine if oil- and gas-facility emissions prospectively measured as airborne sulfur dioxide and volatile organic compounds (VOCs) were associated with immunomodulation in neonatal beef calves, veterinarians collected samples from 325 calves from 60 western Canadian herds in the spring of 2002. Researchers assessed immune system effects by enumerating B-lymphocytes and specific T-lymphocyte subtypes (CD4, CD8, gammadelta, and WC1) in peripheral circulation using flow cytometry. They estimated in utero exposure for each calf from the earliest possible breeding date of the dam to the calving date, using air-quality data from passive monitors installed in pastures and wintering areas.

Associations between immune function in yearling beef cattle and airborne polycyclic aromatic hydrocarbons and PM1.0 near oil and natural gas field facilities.

Researchers determined the potential associations between exposure to airborne fine particulate matter (ie, particulate matter that is < 1 microm in diameter, or PM1.0) and polycyclic aromatic hydrocarbons (PAHs) and immune system function in beef cattle by using blood samples collected from yearling cattle in 22 herds in the spring of 2002. The herds were located at variable distances from industry field facilities in the major oil- and gas-producing areas of western Canada.

Molecular biology of Hodgkin's and Reed/Sternberg cells in Hodgkin's lymphoma.

Hodgkin's and Reed/Sternberg (HRS) cells, the tumour cells in classical Hodgkin's lymphoma (HL), represent transformed B cells in nearly all cases. The detection of destructive somatic mutations in the rearranged immunoglobulin (Ig) genes of HRS cells in classical HL indicated that they originate from preapoptotic germinal centre (GC) B cells that lost the capacity to express a high-affinity B-cell receptor (BCR). Several aberrantly activated signalling pathways and transcription factors have been identified that contribute to the rescue of HRS cells from apoptosis.

Transformation of BCR-deficient germinal-center B cells by EBV supports a major role of the virus in the pathogenesis of Hodgkin and posttransplantation lymphomas.

In classic Hodgkin lymphoma (HL) and posttransplantation lymphoproliferative disease (PTLD), 2 malignancies frequently associated with Epstein-Barr virus (EBV), the tumor cells often appear to derive from B-cell receptor (BCR)-deficient and therefore preapoptotic germinal center (GC) B cells. To test whether EBV can rescue BCR-less GC B cells, we infected human tonsillar CD77+ GC B cells in vitro with EBV. More than 60 monoclonal lymphoblastoid cell lines (LCLs) were established.

Absence of immunoglobulin class switch in primary lymphomas of the central nervous system.

Primary lymphomas of the central nervous system (PCNSLs) were investigated for their capacity to perform further maturation steps. We studied a series of 11 PCNSLs derived from immunocompetent patients for immunoglobulin (Ig) class switch recombination (CSR) by performing reverse transcriptase-polymerase chain reaction (RT-PCR) for transcripts of Ig constant region gene segments (IGHC). This analysis revealed exclusive transcription of IgM and IgD mRNA in the absence of IgG, IgA, or IgE transcription.

Toxicology review and risk assessment of resorcinol: thyroid effects.

Resorcinol administered at high doses to rodents can disrupt thyroid hormone synthesis and can produce goitrogenic effects. These effects were not seen in a 2-year bioassay at doses of up to 520 mg/kg/day. There are species-specific differences in synthesis, binding, and transport of thyroid hormone that complicate interpretation of goitrogenesis in rodents.

Liposomal bleomycin: increased therapeutic activity and decreased pulmonary toxicity in mice.

Conventional and sterically stabilized liposomes derived from phosphatidylcholine or the antitumor agents, hexadecylphosphocholine and octadecyl-(1,1-dimethyl-4-piperidino-4-yl)-phosphate, as bilayer forming constituents, containing bleomycin, were developed and tested. Liposomal encapsulation of bleomycin enhanced strongly the antitumor activity against P388 leukemia and the Lewis lung carcinoma. This effect was clearly dependent on the size and lipid composition of the bleomycin-containing liposomes.

Lack of UDS activity in the livers of rats exposed to allylisothiocyanate.

Allylisothiocyanate (AITC) has been evaluated for its ability to initiate unscheduled DNA synthesis (UDS) in the livers of male rats in vivo. Specific Pathogen Free outbred albino Hsd/Ola Sprague-Dawley rats were exposed by oral gavage to 37.5 or 125 mg/kg AITC in corn oil and hepatocytes assessed for UDS by autoradiography 2 and 14 h later.

Relative contribution of calories from dietary fat, carbohydrate, and fiber in the promotion of DMBA-induced mammary tumors in Sprague-Dawley rats.

It is well known that caloric restriction inhibits, whereas excess calories promote, mammary tumorigenesis in rats. However, the relative contribution to carcinogenesis by calories derived from fat or from carbohydrate are not well established. To determine the relative effects of calories from fat or from carbohydrate, as well as any interaction of dietary fiber on the promotion of 7,12-dimethylbenz[a]anthracene-induced mammary tumors, we fed isocalorically nine diets containing different ratios of fat, carbohydrate, and fiber to female Sprague-Dawley rats treated with 7,12-dimethylbenz[a]anthracene (30/group).