Project description:Methanol (MeOH) is considered to be a poison in humans because of the alcohol dehydrogenase (ADH)-mediated conversion of MeOH into toxic formaldehyde (FA). Our recent genome-wide analysis of the mouse brain demonstrated that an increase in endogenous MeOH after ADH inhibition led to a significant increase in the plasma MeOH concentration and the modification of mRNA synthesis. These findings suggest endogenous MeOH involvement in homeostasis regulation by controlling mRNA levels. Here, we demonstrate directly that study volunteers displayed increasing concentrations of MeOH and FA in their blood plasma when consuming citrus pectin, ethanol and red wine. A microarray analysis of white blood cells (WBC) in volunteers after pectin intake showed various responses for 30 differentially regulated mRNAs. Most of the mRNAs were somehow involved in the pathogenesis of Alzheimer's disease (AD). There was also a decreased synthesis of hemoglobin mRNA, HBA and HBB, the presence of which in WBC RNA was not a result of red blood cells contamination because erythrocyte-specific marker genes did not show significant change. A qRT-PCR analysis of volunteer WBC after pectin and red wine intake confirmed the complicated dependence between plasma MeOH content and the mRNA accumulation of previously identified genes, namely GAPDH and SNX27, and MME, SORL1, DDIT4, HBA and HBB genes revealed in this study. We hypothesized that human plasma MeOH, which is replenished from endogenous and exogenous sources (diet), has an impact on the WBC mRNA levels of genes involved in AD pathogenesis and signaling. The subjects fasted for 12 hours prior to beginning each experiment and evaluation session. Each volunteer swallowed capsules with PME containing citrus pectin (6 g) (Nittary Pharmaceuticals, VitaLine, Inc., USA). After 120 min blood samples were obtained. Total RNA was isolated from WBCs with TriReagent (MRC, USA) according to the manufacturer’s protocol.
Project description:Methanol (MeOH) is considered to be a poison in humans because of the alcohol dehydrogenase (ADH)-mediated conversion of MeOH into toxic formaldehyde (FA). Our recent genome-wide analysis of the mouse brain demonstrated that an increase in endogenous MeOH after ADH inhibition led to a significant increase in the plasma MeOH concentration and the modification of mRNA synthesis. These findings suggest endogenous MeOH involvement in homeostasis regulation by controlling mRNA levels. Here, we demonstrate directly that study volunteers displayed increasing concentrations of MeOH and FA in their blood plasma when consuming citrus pectin, ethanol and red wine. A microarray analysis of white blood cells (WBC) in volunteers after pectin intake showed various responses for 30 differentially regulated mRNAs. Most of the mRNAs were somehow involved in the pathogenesis of Alzheimer's disease (AD). There was also a decreased synthesis of hemoglobin mRNA, HBA and HBB, the presence of which in WBC RNA was not a result of red blood cells contamination because erythrocyte-specific marker genes did not show significant change. A qRT-PCR analysis of volunteer WBC after pectin and red wine intake confirmed the complicated dependence between plasma MeOH content and the mRNA accumulation of previously identified genes, namely GAPDH and SNX27, and MME, SORL1, DDIT4, HBA and HBB genes revealed in this study. We hypothesized that human plasma MeOH, which is replenished from endogenous and exogenous sources (diet), has an impact on the WBC mRNA levels of genes involved in AD pathogenesis and signaling. The subjects fasted for 12 hours prior to beginning each experiment and evaluation session. Each volunteer swallowed capsules with PME containing citrus pectin (6 g) (Nittary Pharmaceuticals, VitaLine, Inc., USA). After 120 min blood samples were obtained. Total RNA was isolated from WBCs with TriReagent (MRC, USA) according to the manufacturer’s protocol.
Project description:Methanol (MeOH) is considered to be a poison in humans because of the alcohol dehydrogenase (ADH)-mediated conversion of MeOH into toxic formaldehyde (FA). Our recent genome-wide analysis of the mouse brain demonstrated that an increase in endogenous MeOH after ADH inhibition led to a significant increase in the plasma MeOH concentration and the modification of mRNA synthesis. These findings suggest endogenous MeOH involvement in homeostasis regulation by controlling mRNA levels. Here, we demonstrate directly that study volunteers displayed increasing concentrations of MeOH and FA in their blood plasma when consuming citrus pectin, ethanol and red wine. A microarray analysis of white blood cells (WBC) in volunteers after pectin intake showed various responses for 30 differentially regulated mRNAs. Most of the mRNAs were somehow involved in the pathogenesis of Alzheimer's disease (AD). There was also a decreased synthesis of hemoglobin mRNA, HBA and HBB, the presence of which in WBC RNA was not a result of red blood cells contamination because erythrocyte-specific marker genes did not show significant change. A qRT-PCR analysis of volunteer WBC after pectin and red wine intake confirmed the complicated dependence between plasma MeOH content and the mRNA accumulation of previously identified genes, namely GAPDH and SNX27, and MME, SORL1, DDIT4, HBA and HBB genes revealed in this study. We hypothesized that human plasma MeOH, which is replenished from endogenous and exogenous sources (diet), has an impact on the WBC mRNA levels of genes involved in AD pathogenesis and signaling. The subjects fasted for 12 hours prior to beginning each experiment and evaluation session. Each volunteer swallowed capsules with PME containing citrus pectin (6 g) (Nittary Pharmaceuticals, VitaLine, Inc., USA). After 120 min blood samples were obtained. Total RNA was isolated from WBCs with TriReagent (MRC, USA) according to the manufacturer’s protocol.
Project description:Methanol (MeOH) is considered to be a poison in humans because of the alcohol dehydrogenase (ADH)-mediated conversion of MeOH into toxic formaldehyde (FA). Our recent genome-wide analysis of the mouse brain demonstrated that an increase in endogenous MeOH after ADH inhibition led to a significant increase in the plasma MeOH concentration and the modification of mRNA synthesis. These findings suggest endogenous MeOH involvement in homeostasis regulation by controlling mRNA levels. Here, we demonstrate directly that study volunteers displayed increasing concentrations of MeOH and FA in their blood plasma when consuming citrus pectin, ethanol and red wine. A microarray analysis of white blood cells (WBC) in volunteers after pectin intake showed various responses for 30 differentially regulated mRNAs. Most of the mRNAs were somehow involved in the pathogenesis of Alzheimer's disease (AD). There was also a decreased synthesis of hemoglobin mRNA, HBA and HBB, the presence of which in WBC RNA was not a result of red blood cells contamination because erythrocyte-specific marker genes did not show significant change. A qRT-PCR analysis of volunteer WBC after pectin and red wine intake confirmed the complicated dependence between plasma MeOH content and the mRNA accumulation of previously identified genes, namely GAPDH and SNX27, and MME, SORL1, DDIT4, HBA and HBB genes revealed in this study. We hypothesized that human plasma MeOH, which is replenished from endogenous and exogenous sources (diet), has an impact on the WBC mRNA levels of genes involved in AD pathogenesis and signaling.
Project description:Methanol (MeOH) is considered to be a poison in humans because of the alcohol dehydrogenase (ADH)-mediated conversion of MeOH into toxic formaldehyde (FA). Our recent genome-wide analysis of the mouse brain demonstrated that an increase in endogenous MeOH after ADH inhibition led to a significant increase in the plasma MeOH concentration and the modification of mRNA synthesis. These findings suggest endogenous MeOH involvement in homeostasis regulation by controlling mRNA levels. Here, we demonstrate directly that study volunteers displayed increasing concentrations of MeOH and FA in their blood plasma when consuming citrus pectin, ethanol and red wine. A microarray analysis of white blood cells (WBC) in volunteers after pectin intake showed various responses for 30 differentially regulated mRNAs. Most of the mRNAs were somehow involved in the pathogenesis of Alzheimer's disease (AD). There was also a decreased synthesis of hemoglobin mRNA, HBA and HBB, the presence of which in WBC RNA was not a result of red blood cells contamination because erythrocyte-specific marker genes did not show significant change. A qRT-PCR analysis of volunteer WBC after pectin and red wine intake confirmed the complicated dependence between plasma MeOH content and the mRNA accumulation of previously identified genes, namely GAPDH and SNX27, and MME, SORL1, DDIT4, HBA and HBB genes revealed in this study. We hypothesized that human plasma MeOH, which is replenished from endogenous and exogenous sources (diet), has an impact on the WBC mRNA levels of genes involved in AD pathogenesis and signaling.
Project description:Methanol (MeOH) is considered to be a poison in humans because of the alcohol dehydrogenase (ADH)-mediated conversion of MeOH into toxic formaldehyde (FA). Our recent genome-wide analysis of the mouse brain demonstrated that an increase in endogenous MeOH after ADH inhibition led to a significant increase in the plasma MeOH concentration and the modification of mRNA synthesis. These findings suggest endogenous MeOH involvement in homeostasis regulation by controlling mRNA levels. Here, we demonstrate directly that study volunteers displayed increasing concentrations of MeOH and FA in their blood plasma when consuming citrus pectin, ethanol and red wine. A microarray analysis of white blood cells (WBC) in volunteers after pectin intake showed various responses for 30 differentially regulated mRNAs. Most of the mRNAs were somehow involved in the pathogenesis of Alzheimer's disease (AD). There was also a decreased synthesis of hemoglobin mRNA, HBA and HBB, the presence of which in WBC RNA was not a result of red blood cells contamination because erythrocyte-specific marker genes did not show significant change. A qRT-PCR analysis of volunteer WBC after pectin and red wine intake confirmed the complicated dependence between plasma MeOH content and the mRNA accumulation of previously identified genes, namely GAPDH and SNX27, and MME, SORL1, DDIT4, HBA and HBB genes revealed in this study. We hypothesized that human plasma MeOH, which is replenished from endogenous and exogenous sources (diet), has an impact on the WBC mRNA levels of genes involved in AD pathogenesis and signaling.
Project description:Patients with early stage CLL were recruited into the study and administered a course of omega 3 dietary supplements. Expression profiling of each patient was performed at baseline (before administering the supplement) and after consumption of supplements. Patients were divided into two groups according to the level of NFkB activation at baseline, and then within each of the two groups significant changes in gene expression between baseline and the highest dose of supplements consumed were sought. Patients were divided into two groups based on initial NFkB levels being below (low expressers) or above (high expressers) the median NFkB Activity level (2.14x10^6 NFkB Luminescence units/µg protein). Within each group, paired two class SAM was performed using the maximum supplement dose for each patient versus the baseline.
Project description:Dietary fiber degradation is a key function of the human gut microbiota. The aim of this study was to increase our knowledge on the degradation of plant cell wall polysaccharide degradation by a prominent human gut bacterial species, Bacteroides xylanisolvens. The transcriptome analysis of B. xylanisolvens XB1AT revealed the existence of six and two genomic loci dedicated to the degradation of pectins and xylan, respectively. These loci or PUL ("Polysaccharide Utilization Loci") are known to encode enzyme systems in Bacteroides that are specific to a particular polysaccharide. Simple two-way comparisons between pectin or xylan sources (treatment) and glucose or xylose (control), collected during mid- and late-log phase. Three replicates per condition.
Project description:Similar to other plant-parasitic nematodes, root lesion nematodes possess an array of enzymes that are involved in degradation of the plant cell wall. Here we report the identification of a gene encoding a cell wall degrading enzyme, pectin methylesterase PME (EC 3.1.1.11), in the root lesion nematode Pratylenchus penetrans. Both genomic and coding sequences of the gene were cloned for this species, showing the presence of four introns that excluded a potential bacterial contamination. Expression of the Pp-pme gene was localized in the esophageal glands of P. penetrans as determined by in situ hybridization. Temporal expression of Pp-pme in planta was validated for early time points of infection. The possible function and activity of the gene were assessed by transient expression of Pp-pme in N. benthamiana plants via a Potato virus X-based vector. To our knowledge, this is the first report on identification and characterization of a PME gene within the phylum Nematoda.