Diana Hernandez - Academia.edu (original) (raw)
Papers by Diana Hernandez
Human Molecular Genetics, 1999
At least 8% of all human conceptions have major chromosome abnormalities and the frequency of chr... more At least 8% of all human conceptions have major chromosome abnormalities and the frequency of chromosomal syndromes in newborns is >0.5%. Despite these disorders making a large contribution to human morbidity and mortality, we have little understanding of their aetiology and little molecular data on the importance of gene dosage to mammalian cells. Trisomy 21, which results in Down syndrome (DS), is the most frequent aneuploidy in humans (1 in 600 live births, up to 1 in 150 pregnancies world-wide) and is the most common known genetic cause of mental retardation. To investigate the molecular genetics of DS, we report here the creation of mice that carry different human chromosome 21 (Hsa21) fragments as a freely segregating extra chromosome. To produce these 'transchromosomal' animals, we placed a selectable marker into Hsa21 and transferred the chromosome from a human somatic cell line into mouse embryonic stem (ES) cells using irradiation microcell-mediated chromosome transfer (XMMCT). 'Transchromosomal' ES cells containing different Hsa21 regions ranging in size from ∼50 to ∼0.2 Mb have been used to create chimeric mice. These mice maintain Hsa21 sequences and express Hsa21 genes in multiple tissues. This novel use of the XMMCT protocol is applicable to investigations requiring the transfer of large chromosomal regions into ES or other cells and, in particular, the modelling of DS and other human aneuploidy syndromes.
Aids Research and Human Retroviruses, 1991
In the present study inactivated human immunodeficiency virus type 1 (HIV-1) was conjugated to Br... more In the present study inactivated human immunodeficiency virus type 1 (HIV-1) was conjugated to Brucella abortus and tested for immunogenicity in normal and anti-L3T4-treated BALB/c mice. HIV-BA was more immunogenic than uncoupled HIV in normal mice, since 6-fold less virus in HIV-BA preparations elicited higher titer responses than HIV-1 alone. Furthermore, the HIV-BA antibody response reached higher levels before the HIV-1 response. Immunoblot analysis showed that most of the HIV-1 antigens were recognized by antibodies induced by either HIV-1 or HIV-BA. Isotype analysis revealed that HIV-1 induced similar levels of IgG1 and IgG2a antibodies, whereas the IgG2a responses to HIV-BA were more pronounced than the IgG1 response. These different IgG subclass patterns suggest that conjugation of HIV-1 to BA changed the immunogenic nature of HIV-1. The requirement for helper T cells was examined by immunizing mice that were depleted of CD4+ T cells by in vivo anti-L3T4 treatment. Under these conditions the IgG responses to HIV-1 were completely eliminated. Although HIV-BA antibody responses were markedly reduced in anti-L3T4-treated mice, anti-HIV-1 antibodies, mainly of the IgG2a isotype, were produced. The antibodies generated by HIV-1 and HIV-BA immunization were also tested for their ability to inhibit syncytia formed by infecting CD4 + CEM cells with gp160 vaccinia. Sera from normal mice, immunized with either HIV-1 or HIV-BA were capable of inhibiting syncytia. In contrast, following anti-L3T4 treatment, only mice immunized with HIV-BA, but not HIV-1, produced antibodies capable of inhibiting syncytia.
Human Mutation, 2003
Trimethylaminuria (TMAuria), or fish-odor syndrome, is due to defective flavin-containing monooxy... more Trimethylaminuria (TMAuria), or fish-odor syndrome, is due to defective flavin-containing monooxygenase 3 (FMO3). In the liver, this protein catalyzes the NADPH-dependent oxidative metabolism of odorous trimethylamine (TMA), derived in the gut from dietary sources, to nonodorous trimethylamine N-oxide (TMA N-oxide). Affected individuals are unable to carry out this reaction and consequently exude a fishy body odor, due to the secretion of TMA in their breath and sweat and its excretion in their urine. This leads to a variety of psychosocial problems, including disruption of schooling, clinical depression, and attempted suicide. Twelve missense, three nonsense, and one gross deletion mutation are known to cause TMAuria. FMO3 is also a drug-metabolizing enzyme and compromised activity is expected to have implications for the efficacy of drug treatment and the possibility of adverse drug reactions both in TMAuric patients and in the general population. To date eight polymorphic variants, not associated with TMAuria, have been reported. A human FMO3 mutation database was created using MuStar, a locus-specific database system for maintaining data about allelic variants and distributing these via the World Wide Web. The database currently contains 24 entries and is accessible on the World Wide Web via the URL http://human-fmo3.biochem.ucl.ac.uk/Human_FMO3. Additional entries can be submitted via the curator of the database or via a web-based form. Hum Mutat 22:209–213, 2003. © 2003 Wiley-Liss, Inc.
Pharmacogenetics, 2004
Objectives To date, six flavin-containing monooxygenase (FMO) genes have been identified in human... more Objectives To date, six flavin-containing monooxygenase (FMO) genes have been identified in humans, FMOs 1, 2, 3, 4 and 6, which are located within a cluster on chromosome 1, and FMO5, which is located outside the cluster. The objectives were to review and update current knowledge of the structure and expression profiles of these genes and of their mouse counterparts and to determine, via a bioinformatics approach, whether other FMO genes are present in the human and mouse genomes.
Human Mutation, 2003
Trimethylaminuria (TMAuria), or fish-odor syndrome, is due to defective flavin-containing monooxy... more Trimethylaminuria (TMAuria), or fish-odor syndrome, is due to defective flavin-containing monooxygenase 3 (FMO3). In the liver, this protein catalyzes the NADPH-dependent oxidative metabolism of odorous trimethylamine (TMA), derived in the gut from dietary sources, to nonodorous trimethylamine N-oxide (TMA N-oxide). Affected individuals are unable to carry out this reaction and consequently exude a fishy body odor, due to the secretion of TMA in their breath and sweat and its excretion in their urine. This leads to a variety of psychosocial problems, including disruption of schooling, clinical depression, and attempted suicide. Twelve missense, three nonsense, and one gross deletion mutation are known to cause TMAuria. FMO3 is also a drug-metabolizing enzyme and compromised activity is expected to have implications for the efficacy of drug treatment and the possibility of adverse drug reactions both in TMAuric patients and in the general population. To date eight polymorphic variants, not associated with TMAuria, have been reported. A human FMO3 mutation database was created using MuStar, a locus-specific database system for maintaining data about allelic variants and distributing these via the World Wide Web. The database currently contains 24 entries and is accessible on the World Wide Web via the URL http://human-fmo3.biochem.ucl.ac.uk/Human_FMO3. Additional entries can be submitted via the curator of the database or via a web-based form. Hum Mutat 22:209–213, 2003. © 2003 Wiley-Liss, Inc.
Pharmacogenetics, 2004
Objectives To date, six flavin-containing monooxygenase (FMO) genes have been identified in human... more Objectives To date, six flavin-containing monooxygenase (FMO) genes have been identified in humans, FMOs 1, 2, 3, 4 and 6, which are located within a cluster on chromosome 1, and FMO5, which is located outside the cluster. The objectives were to review and update current knowledge of the structure and expression profiles of these genes and of their mouse counterparts and to determine, via a bioinformatics approach, whether other FMO genes are present in the human and mouse genomes.
Biochemical Pharmacology, 2004
The cell-, tissue-, sex-and developmental stage-specific expression profiles of five members of t... more The cell-, tissue-, sex-and developmental stage-specific expression profiles of five members of the flavin-containing monooxygenase (FMO) family, FMO1, 2, 3, 4 and 5, were investigated in 129/SV mice, using isoform-specific antisense RNA probes. In situ hybridization localized FMO1 and 5 mRNAs to the perivenous, and FMO 2, 3 and 4 mRNAs to the periportal, regions of the liver. In kidney, each FMO mRNA is localized to the distal and proximal tubules and collecting ducts; FMO1 mRNA is present also in the glomerulus. In lung, FMO1 and 3 mRNAs are expressed in the terminal bronchiole, and FMO1 mRNA also in the alveoli. FMO1 mRNA is present in neurons of the cerebrum and in the choroid plexus. RNase protection assays showed that the most abundant isoform in newborn liver, lung, kidney and brain, and in adult lung and kidney is FMO1, but in adult liver FMO5 is present in greatest amounts. In liver, lung and kidney, expression of Fmo1, 3 and 5 peaks at 3 or 5 weeks of age, but in the brain, Fmo1 expression is greatest in newborns. In the kidney, FMO5 mRNA abundance is fourfold greater in males than in females, at all stages of development. Our results demonstrate that Fmo1, 2, 3, 4 and 5 exhibit distinct cell-, tissue-, sex-and developmental stage-specific patterns of expression. # 2004 Elsevier Inc. All rights reserved.
Biochemical Pharmacology, 2004
The cell-, tissue-, sex- and developmental stage-specific expression profiles of five members of ... more The cell-, tissue-, sex- and developmental stage-specific expression profiles of five members of the flavin-containing monooxygenase (FMO) family, FMO1, 2, 3, 4 and 5, were investigated in 129/SV mice, using isoform-specific antisense RNA probes. In situ hybridization localized FMO1 and 5 mRNAs to the perivenous, and FMO 2, 3 and 4 mRNAs to the periportal, regions of the liver. In kidney, each FMO mRNA is localized to the distal and proximal tubules and collecting ducts; FMO1 mRNA is present also in the glomerulus. In lung, FMO1 and 3 mRNAs are expressed in the terminal bronchiole, and FMO1 mRNA also in the alveoli. FMO1 mRNA is present in neurons of the cerebrum and in the choroid plexus. RNase protection assays showed that the most abundant isoform in newborn liver, lung, kidney and brain, and in adult lung and kidney is FMO1, but in adult liver FMO5 is present in greatest amounts. In liver, lung and kidney, expression of Fmo1, 3 and 5 peaks at 3 or 5 weeks of age, but in the brain, Fmo1 expression is greatest in newborns. In the kidney, FMO5 mRNA abundance is fourfold greater in males than in females, at all stages of development. Our results demonstrate that Fmo1, 2, 3, 4 and 5 exhibit distinct cell-, tissue-, sex- and developmental stage-specific patterns of expression.
Human Mutation, 2003
Trimethylaminuria (TMAuria), or fish-odor syndrome, is due to defective flavin-containing monooxy... more Trimethylaminuria (TMAuria), or fish-odor syndrome, is due to defective flavin-containing monooxygenase 3 (FMO3). In the liver, this protein catalyzes the NADPH-dependent oxidative metabolism of odorous trimethylamine (TMA), derived in the gut from dietary sources, to nonodorous trimethylamine N-oxide (TMA N-oxide). Affected individuals are unable to carry out this reaction and consequently exude a fishy body odor, due to the secretion of TMA in their breath and sweat and its excretion in their urine. This leads to a variety of psychosocial problems, including disruption of schooling, clinical depression, and attempted suicide. Twelve missense, three nonsense, and one gross deletion mutation are known to cause TMAuria. FMO3 is also a drug-metabolizing enzyme and compromised activity is expected to have implications for the efficacy of drug treatment and the possibility of adverse drug reactions both in TMAuric patients and in the general population. To date eight polymorphic variants, not associated with TMAuria, have been reported. A human FMO3 mutation database was created using MuStar, a locus-specific database system for maintaining data about allelic variants and distributing these via the World Wide Web. The database currently contains 24 entries and is accessible on the World Wide Web via the URL http://human-fmo3.biochem.ucl.ac.uk/Human_FMO3. Additional entries can be submitted via the curator of the database or via a web-based form. Hum Mutat 22:209–213, 2003. © 2003 Wiley-Liss, Inc.
Pharmacogenetics, 2004
Objectives To date, six flavin-containing monooxygenase (FMO) genes have been identified in human... more Objectives To date, six flavin-containing monooxygenase (FMO) genes have been identified in humans, FMOs 1, 2, 3, 4 and 6, which are located within a cluster on chromosome 1, and FMO5, which is located outside the cluster. The objectives were to review and update current knowledge of the structure and expression profiles of these genes and of their mouse counterparts and to determine, via a bioinformatics approach, whether other FMO genes are present in the human and mouse genomes.
Biochemical Pharmacology, 2004
The cell-, tissue-, sex-and developmental stage-specific expression profiles of five members of t... more The cell-, tissue-, sex-and developmental stage-specific expression profiles of five members of the flavin-containing monooxygenase (FMO) family, FMO1, 2, 3, 4 and 5, were investigated in 129/SV mice, using isoform-specific antisense RNA probes. In situ hybridization localized FMO1 and 5 mRNAs to the perivenous, and FMO 2, 3 and 4 mRNAs to the periportal, regions of the liver. In kidney, each FMO mRNA is localized to the distal and proximal tubules and collecting ducts; FMO1 mRNA is present also in the glomerulus. In lung, FMO1 and 3 mRNAs are expressed in the terminal bronchiole, and FMO1 mRNA also in the alveoli. FMO1 mRNA is present in neurons of the cerebrum and in the choroid plexus. RNase protection assays showed that the most abundant isoform in newborn liver, lung, kidney and brain, and in adult lung and kidney is FMO1, but in adult liver FMO5 is present in greatest amounts. In liver, lung and kidney, expression of Fmo1, 3 and 5 peaks at 3 or 5 weeks of age, but in the brain, Fmo1 expression is greatest in newborns. In the kidney, FMO5 mRNA abundance is fourfold greater in males than in females, at all stages of development. Our results demonstrate that Fmo1, 2, 3, 4 and 5 exhibit distinct cell-, tissue-, sex-and developmental stage-specific patterns of expression. # 2004 Elsevier Inc. All rights reserved.
Environmental Pollution, 2006
Pig-slurry application to soil decreased Cu(II) and Zn(II) binding affinities of soil humic acids.
Geoderma, 2007
Soil amendment with sewage sludge (SS) from municipal wastewater treatment plants is nowadays a c... more Soil amendment with sewage sludge (SS) from municipal wastewater treatment plants is nowadays a common practice for both increasing soil organic matter and nutrient contents and waste disposal. However, the application of organic amendments that are not sufficiently mature and stable may adversely affect soil properties. Composting and thermal drying are treatments designed to minimize these possible deleterious effects and to facilitate the use of SS as a soil organic amendment. In this work, an arid soil either unamended or amended with composted sewage sludge (CSS) or thermally-dried sewage sludge (TSS) was moistened to an equivalent of 60% soil water holding capacity and incubated for 60 days at 28°C. The C-CO 2 emission from the samples was periodically measured in order to study C mineralization kinetics and evaluate the use of these SS as organic amendments. In all cases, C mineralization decreased after the first day. TSS-amended soil showed significantly higher mineralization rates than unamended and CSS-amended soils during the incubation period. The data of cumulative C-CO 2 released from unamended and SS-amended soils were fitted to six different kinetic models. A two simultaneous reactions model, which considers two organic pools with different degree of biodegradability, was found to be the most appropriate to describe C mineralization kinetics for all the soils. The parameters derived from this model suggested a larger presence of easily biodegradable compounds in TSS-amended soil than in CSS-amended soil, which in turn presented a C mineralization pattern very similar to that of the unamended soil. Furthermore, net mineralization coefficient and complementary mineralization coefficient were calculated from C mineralization data. The largest losses of C were measured for TSS-amended soil probably due to an extended microbial activity. The results obtained thus indicated that CSS is more efficient for increasing total organic C in arid soils.
Human Molecular Genetics, 1999
At least 8% of all human conceptions have major chromosome abnormalities and the frequency of chr... more At least 8% of all human conceptions have major chromosome abnormalities and the frequency of chromosomal syndromes in newborns is >0.5%. Despite these disorders making a large contribution to human morbidity and mortality, we have little understanding of their aetiology and little molecular data on the importance of gene dosage to mammalian cells. Trisomy 21, which results in Down syndrome (DS), is the most frequent aneuploidy in humans (1 in 600 live births, up to 1 in 150 pregnancies world-wide) and is the most common known genetic cause of mental retardation. To investigate the molecular genetics of DS, we report here the creation of mice that carry different human chromosome 21 (Hsa21) fragments as a freely segregating extra chromosome. To produce these 'transchromosomal' animals, we placed a selectable marker into Hsa21 and transferred the chromosome from a human somatic cell line into mouse embryonic stem (ES) cells using irradiation microcell-mediated chromosome transfer (XMMCT). 'Transchromosomal' ES cells containing different Hsa21 regions ranging in size from ∼50 to ∼0.2 Mb have been used to create chimeric mice. These mice maintain Hsa21 sequences and express Hsa21 genes in multiple tissues. This novel use of the XMMCT protocol is applicable to investigations requiring the transfer of large chromosomal regions into ES or other cells and, in particular, the modelling of DS and other human aneuploidy syndromes.
Aids Research and Human Retroviruses, 1991
In the present study inactivated human immunodeficiency virus type 1 (HIV-1) was conjugated to Br... more In the present study inactivated human immunodeficiency virus type 1 (HIV-1) was conjugated to Brucella abortus and tested for immunogenicity in normal and anti-L3T4-treated BALB/c mice. HIV-BA was more immunogenic than uncoupled HIV in normal mice, since 6-fold less virus in HIV-BA preparations elicited higher titer responses than HIV-1 alone. Furthermore, the HIV-BA antibody response reached higher levels before the HIV-1 response. Immunoblot analysis showed that most of the HIV-1 antigens were recognized by antibodies induced by either HIV-1 or HIV-BA. Isotype analysis revealed that HIV-1 induced similar levels of IgG1 and IgG2a antibodies, whereas the IgG2a responses to HIV-BA were more pronounced than the IgG1 response. These different IgG subclass patterns suggest that conjugation of HIV-1 to BA changed the immunogenic nature of HIV-1. The requirement for helper T cells was examined by immunizing mice that were depleted of CD4+ T cells by in vivo anti-L3T4 treatment. Under these conditions the IgG responses to HIV-1 were completely eliminated. Although HIV-BA antibody responses were markedly reduced in anti-L3T4-treated mice, anti-HIV-1 antibodies, mainly of the IgG2a isotype, were produced. The antibodies generated by HIV-1 and HIV-BA immunization were also tested for their ability to inhibit syncytia formed by infecting CD4 + CEM cells with gp160 vaccinia. Sera from normal mice, immunized with either HIV-1 or HIV-BA were capable of inhibiting syncytia. In contrast, following anti-L3T4 treatment, only mice immunized with HIV-BA, but not HIV-1, produced antibodies capable of inhibiting syncytia.
Human Mutation, 2003
Trimethylaminuria (TMAuria), or fish-odor syndrome, is due to defective flavin-containing monooxy... more Trimethylaminuria (TMAuria), or fish-odor syndrome, is due to defective flavin-containing monooxygenase 3 (FMO3). In the liver, this protein catalyzes the NADPH-dependent oxidative metabolism of odorous trimethylamine (TMA), derived in the gut from dietary sources, to nonodorous trimethylamine N-oxide (TMA N-oxide). Affected individuals are unable to carry out this reaction and consequently exude a fishy body odor, due to the secretion of TMA in their breath and sweat and its excretion in their urine. This leads to a variety of psychosocial problems, including disruption of schooling, clinical depression, and attempted suicide. Twelve missense, three nonsense, and one gross deletion mutation are known to cause TMAuria. FMO3 is also a drug-metabolizing enzyme and compromised activity is expected to have implications for the efficacy of drug treatment and the possibility of adverse drug reactions both in TMAuric patients and in the general population. To date eight polymorphic variants, not associated with TMAuria, have been reported. A human FMO3 mutation database was created using MuStar, a locus-specific database system for maintaining data about allelic variants and distributing these via the World Wide Web. The database currently contains 24 entries and is accessible on the World Wide Web via the URL http://human-fmo3.biochem.ucl.ac.uk/Human_FMO3. Additional entries can be submitted via the curator of the database or via a web-based form. Hum Mutat 22:209–213, 2003. © 2003 Wiley-Liss, Inc.
Pharmacogenetics, 2004
Objectives To date, six flavin-containing monooxygenase (FMO) genes have been identified in human... more Objectives To date, six flavin-containing monooxygenase (FMO) genes have been identified in humans, FMOs 1, 2, 3, 4 and 6, which are located within a cluster on chromosome 1, and FMO5, which is located outside the cluster. The objectives were to review and update current knowledge of the structure and expression profiles of these genes and of their mouse counterparts and to determine, via a bioinformatics approach, whether other FMO genes are present in the human and mouse genomes.
Human Mutation, 2003
Trimethylaminuria (TMAuria), or fish-odor syndrome, is due to defective flavin-containing monooxy... more Trimethylaminuria (TMAuria), or fish-odor syndrome, is due to defective flavin-containing monooxygenase 3 (FMO3). In the liver, this protein catalyzes the NADPH-dependent oxidative metabolism of odorous trimethylamine (TMA), derived in the gut from dietary sources, to nonodorous trimethylamine N-oxide (TMA N-oxide). Affected individuals are unable to carry out this reaction and consequently exude a fishy body odor, due to the secretion of TMA in their breath and sweat and its excretion in their urine. This leads to a variety of psychosocial problems, including disruption of schooling, clinical depression, and attempted suicide. Twelve missense, three nonsense, and one gross deletion mutation are known to cause TMAuria. FMO3 is also a drug-metabolizing enzyme and compromised activity is expected to have implications for the efficacy of drug treatment and the possibility of adverse drug reactions both in TMAuric patients and in the general population. To date eight polymorphic variants, not associated with TMAuria, have been reported. A human FMO3 mutation database was created using MuStar, a locus-specific database system for maintaining data about allelic variants and distributing these via the World Wide Web. The database currently contains 24 entries and is accessible on the World Wide Web via the URL http://human-fmo3.biochem.ucl.ac.uk/Human_FMO3. Additional entries can be submitted via the curator of the database or via a web-based form. Hum Mutat 22:209–213, 2003. © 2003 Wiley-Liss, Inc.
Pharmacogenetics, 2004
Objectives To date, six flavin-containing monooxygenase (FMO) genes have been identified in human... more Objectives To date, six flavin-containing monooxygenase (FMO) genes have been identified in humans, FMOs 1, 2, 3, 4 and 6, which are located within a cluster on chromosome 1, and FMO5, which is located outside the cluster. The objectives were to review and update current knowledge of the structure and expression profiles of these genes and of their mouse counterparts and to determine, via a bioinformatics approach, whether other FMO genes are present in the human and mouse genomes.
Biochemical Pharmacology, 2004
The cell-, tissue-, sex-and developmental stage-specific expression profiles of five members of t... more The cell-, tissue-, sex-and developmental stage-specific expression profiles of five members of the flavin-containing monooxygenase (FMO) family, FMO1, 2, 3, 4 and 5, were investigated in 129/SV mice, using isoform-specific antisense RNA probes. In situ hybridization localized FMO1 and 5 mRNAs to the perivenous, and FMO 2, 3 and 4 mRNAs to the periportal, regions of the liver. In kidney, each FMO mRNA is localized to the distal and proximal tubules and collecting ducts; FMO1 mRNA is present also in the glomerulus. In lung, FMO1 and 3 mRNAs are expressed in the terminal bronchiole, and FMO1 mRNA also in the alveoli. FMO1 mRNA is present in neurons of the cerebrum and in the choroid plexus. RNase protection assays showed that the most abundant isoform in newborn liver, lung, kidney and brain, and in adult lung and kidney is FMO1, but in adult liver FMO5 is present in greatest amounts. In liver, lung and kidney, expression of Fmo1, 3 and 5 peaks at 3 or 5 weeks of age, but in the brain, Fmo1 expression is greatest in newborns. In the kidney, FMO5 mRNA abundance is fourfold greater in males than in females, at all stages of development. Our results demonstrate that Fmo1, 2, 3, 4 and 5 exhibit distinct cell-, tissue-, sex-and developmental stage-specific patterns of expression. # 2004 Elsevier Inc. All rights reserved.
Biochemical Pharmacology, 2004
The cell-, tissue-, sex- and developmental stage-specific expression profiles of five members of ... more The cell-, tissue-, sex- and developmental stage-specific expression profiles of five members of the flavin-containing monooxygenase (FMO) family, FMO1, 2, 3, 4 and 5, were investigated in 129/SV mice, using isoform-specific antisense RNA probes. In situ hybridization localized FMO1 and 5 mRNAs to the perivenous, and FMO 2, 3 and 4 mRNAs to the periportal, regions of the liver. In kidney, each FMO mRNA is localized to the distal and proximal tubules and collecting ducts; FMO1 mRNA is present also in the glomerulus. In lung, FMO1 and 3 mRNAs are expressed in the terminal bronchiole, and FMO1 mRNA also in the alveoli. FMO1 mRNA is present in neurons of the cerebrum and in the choroid plexus. RNase protection assays showed that the most abundant isoform in newborn liver, lung, kidney and brain, and in adult lung and kidney is FMO1, but in adult liver FMO5 is present in greatest amounts. In liver, lung and kidney, expression of Fmo1, 3 and 5 peaks at 3 or 5 weeks of age, but in the brain, Fmo1 expression is greatest in newborns. In the kidney, FMO5 mRNA abundance is fourfold greater in males than in females, at all stages of development. Our results demonstrate that Fmo1, 2, 3, 4 and 5 exhibit distinct cell-, tissue-, sex- and developmental stage-specific patterns of expression.
Human Mutation, 2003
Trimethylaminuria (TMAuria), or fish-odor syndrome, is due to defective flavin-containing monooxy... more Trimethylaminuria (TMAuria), or fish-odor syndrome, is due to defective flavin-containing monooxygenase 3 (FMO3). In the liver, this protein catalyzes the NADPH-dependent oxidative metabolism of odorous trimethylamine (TMA), derived in the gut from dietary sources, to nonodorous trimethylamine N-oxide (TMA N-oxide). Affected individuals are unable to carry out this reaction and consequently exude a fishy body odor, due to the secretion of TMA in their breath and sweat and its excretion in their urine. This leads to a variety of psychosocial problems, including disruption of schooling, clinical depression, and attempted suicide. Twelve missense, three nonsense, and one gross deletion mutation are known to cause TMAuria. FMO3 is also a drug-metabolizing enzyme and compromised activity is expected to have implications for the efficacy of drug treatment and the possibility of adverse drug reactions both in TMAuric patients and in the general population. To date eight polymorphic variants, not associated with TMAuria, have been reported. A human FMO3 mutation database was created using MuStar, a locus-specific database system for maintaining data about allelic variants and distributing these via the World Wide Web. The database currently contains 24 entries and is accessible on the World Wide Web via the URL http://human-fmo3.biochem.ucl.ac.uk/Human_FMO3. Additional entries can be submitted via the curator of the database or via a web-based form. Hum Mutat 22:209–213, 2003. © 2003 Wiley-Liss, Inc.
Pharmacogenetics, 2004
Objectives To date, six flavin-containing monooxygenase (FMO) genes have been identified in human... more Objectives To date, six flavin-containing monooxygenase (FMO) genes have been identified in humans, FMOs 1, 2, 3, 4 and 6, which are located within a cluster on chromosome 1, and FMO5, which is located outside the cluster. The objectives were to review and update current knowledge of the structure and expression profiles of these genes and of their mouse counterparts and to determine, via a bioinformatics approach, whether other FMO genes are present in the human and mouse genomes.
Biochemical Pharmacology, 2004
The cell-, tissue-, sex-and developmental stage-specific expression profiles of five members of t... more The cell-, tissue-, sex-and developmental stage-specific expression profiles of five members of the flavin-containing monooxygenase (FMO) family, FMO1, 2, 3, 4 and 5, were investigated in 129/SV mice, using isoform-specific antisense RNA probes. In situ hybridization localized FMO1 and 5 mRNAs to the perivenous, and FMO 2, 3 and 4 mRNAs to the periportal, regions of the liver. In kidney, each FMO mRNA is localized to the distal and proximal tubules and collecting ducts; FMO1 mRNA is present also in the glomerulus. In lung, FMO1 and 3 mRNAs are expressed in the terminal bronchiole, and FMO1 mRNA also in the alveoli. FMO1 mRNA is present in neurons of the cerebrum and in the choroid plexus. RNase protection assays showed that the most abundant isoform in newborn liver, lung, kidney and brain, and in adult lung and kidney is FMO1, but in adult liver FMO5 is present in greatest amounts. In liver, lung and kidney, expression of Fmo1, 3 and 5 peaks at 3 or 5 weeks of age, but in the brain, Fmo1 expression is greatest in newborns. In the kidney, FMO5 mRNA abundance is fourfold greater in males than in females, at all stages of development. Our results demonstrate that Fmo1, 2, 3, 4 and 5 exhibit distinct cell-, tissue-, sex-and developmental stage-specific patterns of expression. # 2004 Elsevier Inc. All rights reserved.
Environmental Pollution, 2006
Pig-slurry application to soil decreased Cu(II) and Zn(II) binding affinities of soil humic acids.
Geoderma, 2007
Soil amendment with sewage sludge (SS) from municipal wastewater treatment plants is nowadays a c... more Soil amendment with sewage sludge (SS) from municipal wastewater treatment plants is nowadays a common practice for both increasing soil organic matter and nutrient contents and waste disposal. However, the application of organic amendments that are not sufficiently mature and stable may adversely affect soil properties. Composting and thermal drying are treatments designed to minimize these possible deleterious effects and to facilitate the use of SS as a soil organic amendment. In this work, an arid soil either unamended or amended with composted sewage sludge (CSS) or thermally-dried sewage sludge (TSS) was moistened to an equivalent of 60% soil water holding capacity and incubated for 60 days at 28°C. The C-CO 2 emission from the samples was periodically measured in order to study C mineralization kinetics and evaluate the use of these SS as organic amendments. In all cases, C mineralization decreased after the first day. TSS-amended soil showed significantly higher mineralization rates than unamended and CSS-amended soils during the incubation period. The data of cumulative C-CO 2 released from unamended and SS-amended soils were fitted to six different kinetic models. A two simultaneous reactions model, which considers two organic pools with different degree of biodegradability, was found to be the most appropriate to describe C mineralization kinetics for all the soils. The parameters derived from this model suggested a larger presence of easily biodegradable compounds in TSS-amended soil than in CSS-amended soil, which in turn presented a C mineralization pattern very similar to that of the unamended soil. Furthermore, net mineralization coefficient and complementary mineralization coefficient were calculated from C mineralization data. The largest losses of C were measured for TSS-amended soil probably due to an extended microbial activity. The results obtained thus indicated that CSS is more efficient for increasing total organic C in arid soils.