Publications by authors named "Marilyn Henderson"

Cell walls are crucial for the integrity and function of all land plants and are of central importance in human health, livestock production, and as a source of renewable bioenergy. Many enzymes that mediate the biosynthesis of cell wall polysaccharides are encoded by members of the large () gene superfamily. Here, we analyzed 29 sequenced genomes and 17 transcriptomes to revise the phylogeny of the gene superfamily in angiosperms.

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Metabolism is a key health risk factor following exposures to pro-carcinogenic polycyclic aromatic hydrocarbons (PAHs) such as dibenzo[def,p]chrysene (DBC), an IARC classified 2A probable human carcinogen. Human exposure to PAHs occurs primarily from the diet in nonsmokers. However, little data is available on the metabolism and pharmacokinetics in humans of high molecular weight PAHs (≥4 aromatic rings), including DBC.

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Background: Setaria viridis has emerged as a model species for the larger C4 grasses. Here the cellulose synthase (CesA) superfamily has been defined, with an emphasis on the amounts and distribution of (1,3;1,4)-β-glucan, a cell wall polysaccharide that is characteristic of the grasses and is of considerable value for human health.

Methods: Orthologous relationship of the CesA and Poales-specific cellulose synthase-like (Csl) genes among Setaria italica (Si), Sorghum bicolor (Sb), Oryza sativa (Os), Brachypodium distachyon (Bradi) and Hordeum vulgare (Hv) were compared using bioinformatics analysis.

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Plant biomass from different species is heterogeneous, and this diversity in composition can be mined to identify materials of value to fuel and chemical industries. Agave produces high yields of energy-rich biomass, and the sugar-rich stem tissue has traditionally been used to make alcoholic beverages. Here, the compositions of Agave americana and Agave tequilana leaves are determined, particularly in the context of bioethanol production.

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Global grape production could generate up to 13 Mt/yr of wasted biomass. The compositions of Cabernet Sauvignon (red marc) and Sauvignon Blanc (white marc) were analyzed with a view to using marc as raw material for biofuel production. On a dry weight basis, 31-54% w/w of the grape marc consisted of carbohydrate, of which 47-80% was soluble in aqueous media.

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Background: The ability to increase cellulose content and improve the stem strength of cereals could have beneficial applications in stem lodging and producing crops with higher cellulose content for biofuel feedstocks. Here, such potential is explored in the commercially important crop barley through the manipulation of cellulose synthase genes (CesA).

Results: Barley plants transformed with primary cell wall (PCW) and secondary cell wall (SCW) barley cellulose synthase (HvCesA) cDNAs driven by the CaMV 35S promoter, were analysed for growth and morphology, transcript levels, cellulose content, stem strength, tissue morphology and crystalline cellulose distribution.

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Heterodera avenae (cereal cyst nematode, CCN) infects the roots of barley (Hordeum vulgare) forming syncytial feeding sites. In resistant host plants, relatively few females develop to maturity. Little is known about the physiological and biochemical changes induced during CCN infection.

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In cereals, the presence of soluble polysaccharides including (1,3;1,4)-β-glucan has downstream implications for human health, animal feed and biofuel applications. Sorghum bicolor (L.) Moench is a versatile crop, but there are limited reports regarding the content of such soluble polysaccharides.

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In plants, cell walls are one of the first lines of defence for protecting cells from successful invasion by fungal pathogens and are a major factor in basal host resistance. For the plant cell to block penetration attempts, it must adapt its cell wall to withstand the physical and chemical forces applied by the fungus. Papillae that have been effective in preventing penetration by pathogens are traditionally believed to contain callose as the main polysaccharide component.

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  • This study investigates how the mammalian flavin-containing monooxygenase (FMO) processes drugs with soft nucleophilic heteroatoms, specifically focusing on thiocarbamides and thiones.
  • Using LC-MS/MS, the researchers found that hFMO primarily converted thioureas to sulfenic acid and thiones to sulfinic acid, which then transformed into imidazole.
  • The study highlights differences in FMO isoforms across ethnicities, noting that hFMO2 is prevalent in the lungs of many mammals and is critical in metabolizing potentially toxic thioureas, while hFMO1 and hFMO3 vary in their efficiency for thione substrates.
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  • Flavin-containing monooxygenase (FMO) enzymes oxidize drugs and xenobiotics via a C4a hydroperoxy-FAD intermediate, producing hydrogen peroxide (H₂O₂) alongside oxygen consumption.
  • The genetic polymorphisms S195L and N413K in FMO2 (important in the lung) showed that S195L had significantly higher H₂O₂ production, especially without substrate, compared to the ancestral form and N413K variant.
  • The findings suggest that FMO, particularly the S195L variant, could increase the toxicity of certain xenobiotics by generating harmful metabolites and reactive oxygen species (ROS).
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To explain the low levels of starch, high levels of (1,3;1,4)-β-glucan, and thick cell walls in grains of Brachypodium distachyon L. relative to those in other Pooideae, aspects of grain development were compared between B. distachyon and barley (Hordeum vulgare L.

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Flavin-containing monooxygenases often are thought not to be inducible but we recently demonstrated aryl hydrocarbon receptor (AHR)-dependent induction of FMO mRNAs in mouse liver by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (Celius et al., Drug Metab Dispos 36:2499, 2008). We now evaluated FMO induction by other AHR ligands and xenobiotic chemicals in vivo and in mouse Hepa1c1c7 hepatoma cells (Hepa-1).

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Cell walls in commercially important cereals and grasses are characterized by the presence of (1,3;1,4)-β-d-glucans. These polysaccharides are beneficial constituents of human diets, where they can reduce the risk of hypercholesterolemia, type II diabetes, obesity and colorectal cancer. The biosynthesis of cell wall (1,3;1,4)-β-d-glucans in the Poaceae is mediated, in part at least, by the cellulose synthase-like CslF family of genes.

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Article Synopsis
  • The study focuses on the human flavin-containing monooxygenase isoform 2 (FMO2.1), which is linked to certain alleles found primarily in African and Hispanic individuals, highlighting its genetic uniqueness.
  • It examines two mutations, S195L and N413K, and how they affect the enzyme's activity, particularly showing that S195L results in significantly reduced activity under various conditions while N413K shows both higher activity and increased sensitivity to heat.
  • The findings provide insight into the functional consequences of these mutations on enzyme behavior, enhancing our understanding of the structure and function of mammalian FMO enzymes.
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  • - Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a global health issue, with a significant concern around multi-drug resistant strains that require the use of toxic second-line medications like ethionamide (ETA).
  • - ETA must be bioactivated for toxicity, and both M. tuberculosis and mammalian flavin-containing monooxygenases (FMOs) are involved in converting ETA to its active form, primarily the S-oxide (ETASO), with human and mouse models showing similar metabolic pathways.
  • - The study highlights potential factors influencing the effectiveness and toxicity of ETA treatment, including the role of specific FMOs in the liver and lung, and suggests that genetic variations in FMO2 could impact therapeutic outcomes
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  • The study investigates the roles of active versus inactive flavin-containing monooxygenase 2 (FMO2) in drug metabolism and individual sensitivity, highlighting known ethnic variations in FMO expression.
  • Researchers used real-time PCR on lung and liver samples from different mouse strains to find a mouse model closely resembling human FMO expression, particularly focusing on FMO2 predominance.
  • Results showed that while FMO2 was predominant in lung samples, both FMO1 and FMO3 levels were significant, with the dual knockout of FMO1 and FMO2 being essential to accurately simulate human lung FMO activity patterns.
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  • Flavin-containing monooxygenases (FMOs), especially FMO3, play a key role in how drugs and toxins are processed in the body, with genetic variations affecting this function among different populations.
  • In a study of various ethnic groups, three novel FMO3 variants were identified, with one, N61K, showing no activity and differing allele frequencies between non-Latino whites and African Americans, but absent in Hispanics.
  • The research revealed distinct haplotype frequencies among these populations, indicating greater diversity in African Americans and specific variant clusters associated with different activity levels in FMO3 across the groups.
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  • Flavin-containing monooxygenases (FMO) are important enzymes that help break down drugs and chemicals, but their structural similarities to other proteins remain unclear, complicating our understanding of their metabolism differences.* -
  • Researchers modified rabbit FMO2 (rF2) by making specific mutations to enhance its solubility and reduce aggregation, with one significant change being the deletion of 26 amino acids (Delta26) from the protein.* -
  • The Delta26 variants not only maintained normal enzymatic activity but also improved protein yield in low and high salt conditions, making them better candidates for crystallization studies essential for further research on FMO structures.*
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The evolution of behavioral health care financing and delivery has led to a wide variety of arrangements connecting consumers to behavioral health services. In this paper, we present a typology based on three distinguishing features of behavioral health arrangements along which there is a high degree of variability and this variability has been shown to affect the cost and quality of behavioral health care: (1) the extent to which sponsor oversight over care is outsourced by way of contracts rather than performed directly; (2) whether financing for behavioral health is partitioned from health care financing overall; and (3) the amount of financial risk shared by the sponsor with third parties.

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The authors report on a 2002 national survey of mental health mutual support groups (MSG) and self-help organizations (SHO) run by and for mental health consumers and/or family members, and consumer-operated services (COS). They found 7,467 of these groups and organizations-3,315 MSGs, 3,019 SHOs, and 1,133 COSs-greatly eclipsing the number of traditional mental health organizations (4,546). MSGs reported that 41,363 people attended their last meetings.

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Article Synopsis
  • - The study examines two alleles of the flavin-containing monooxygenase 2 (FMO2) gene, noting that the major allele (FMO2*2) produces an inactive protein, while the minor allele (FMO2*1) results in an active protein, primarily found in African- and Hispanic-American populations.
  • - Researchers aimed to analyze the prevalence of four specific SNPs in a group of Hispanic individuals and understand how these genetic variations affect the function of the FMO2 protein.
  • - Findings showed that most SNPs were less common in the Hispanic population compared to African-Americans, but the active variant (p.N413 K) was effective like the standard active protein, suggesting individuals with at least
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  • Phorate and disulfoton are organophosphate insecticides containing oxidizable sulfurs, primarily oxidized by flavin-containing monooxygenase (FMO), resulting in sulfoxide metabolites.
  • The major FMO in mammals, FMO2, has variants: FMO2*2 (non-functional) is common in Caucasians and Asians, while FMO2*1 (functional) is present in some individuals of African and Hispanic descent.
  • Studies showed that FMO2.1 efficiently metabolizes these insecticides with lower toxicity, suggesting that individuals with the FMO2*1 allele may have greater resistance to the harmful effects associated with these chemicals when exposed through the lungs.
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Thioureas are oxygenated by flavin-containing monooxygenases (FMOs), forming reactive sulfenic and/or sulfinic acids. Sulfenic acids can reversibly react with GSH and drive oxidative stress through a redox cycle. For this reason, thiourea S-oxygenation is an example of FMO-dependent bioactivation of a xenobiotic.

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