Integrated analysis of whole blood oxylipin and cytokine responses after bacterial, viral, and T cell stimulation reveals new immune networks.

Oxylipins are major immunomodulating mediators, yet studies of inflammation focus mainly on cytokines. Here, using a standardized whole-blood stimulation system, we characterized the oxylipin-driven inflammatory responses to various stimuli and their relationships with cytokine responses. We performed a pilot study in 25 healthy individuals using 6 different stimuli: 2 bacterial stimuli (LPS and live BCG), 2 viral stimuli (vaccine-grade poly I:C and live H1N1 attenuated influenza), an enterotoxin superantigen and a Null control.

The Arabidopsis B3 domain protein VERNALIZATION1 (VRN1) is involved in processes essential for development, with structural and mutational studies revealing its DNA-binding surface.

The B3 DNA-binding domain is a plant-specific domain found throughout the plant kingdom from the alga Chlamydomonas to grasses and flowering plants. Over 100 B3 domain-containing proteins are found in the model plant Arabidopsis thaliana, and one of these is critical for accelerating flowering in response to prolonged cold treatment, an epigenetic process called vernalization. Despite the specific phenotype of genetic vrn1 mutants, the VERNALIZATION1 (VRN1) protein localizes throughout the nucleus and shows sequence-nonspecific binding in vitro.

Cyclic peptides arising by evolutionary parallelism via asparaginyl-endopeptidase-mediated biosynthesis.

The cyclic miniprotein Momordica cochinchinensis Trypsin Inhibitor II (MCoTI-II) (34 amino acids) is a potent trypsin inhibitor (TI) and a favored scaffold for drug design. We have cloned the corresponding genes and determined that each precursor protein contains a tandem series of cyclic TIs terminating with the more commonly known, and potentially ancestral, acyclic TI. Expression of the precursor protein in Arabidopsis thaliana showed that production of the cyclic TIs, but not the terminal acyclic TI, depends on asparaginyl endopeptidase (AEP) for maturation.

Albumins and their processing machinery are hijacked for cyclic peptides in sunflower.

The cyclic peptide sunflower trypsin inhibitor 1 (SFTI-1) blocks trypsin and is a promising drug lead and protein engineering scaffold. We show that SFTI-1 and the newfound SFT-L1 are buried within PawS1 and PawS2, precursors for seed storage protein albumins. Proalbumins are matured by asparaginyl endopeptidase, which we show is required to liberate both ends of SFTI-1 as well as to mature PawS1 albumin.

Folate supplementation differently affects uracil content in DNA in the mouse colon and liver.

High folate intake may increase the risk of cancer, especially in the elderly. The present study examined the effects of ageing and dietary folate on uracil misincorporation into DNA, which has a mutagenic effect, in the mouse colon and liver. Old (18 months; n 42) and young (4 months; n 42) male C57BL/6 mice were pair-fed with four different amino acid-defined diets for 20 weeks: folate deplete (0 mg/kg diet); folate replete (2 mg/kg diet); folate supplemented (8 mg/kg diet); folate deplete (0 mg/kg diet) with thymidine supplementation (1·8 g/kg diet).

Ageing, chronic alcohol consumption and folate are determinants of genomic DNA methylation, p16 promoter methylation and the expression of p16 in the mouse colon.

Older age, dietary folate and chronic alcohol consumption are important risk factors for the development of colon cancer. The present study examined the effects of ageing, folate and alcohol on genomic and p16-specific DNA methylation, and p16 expression in the murine colon. Old (aged 18 months; n 70) and young (aged 4 months; n 70) male C57BL/6 mice were pair-fed either a Lieber-DeCarli liquid diet with alcohol (18 % of energy), a Lieber-DeCarli diet with alcohol (18 %) and reduced folate (0.

Polymorphisms in uracil-processing genes, but not one-carbon nutrients, are associated with altered DNA uracil concentrations in an urban Puerto Rican population.

Background: Five genes--UNG, SMUG1, MBD4, TDG, and DUT--are involved in the repair or prevention of uracil misincorporation into DNA, an anomaly that can cause mutagenic events that lead to cancer. Little is known about the determinants of uracil misincorporation, including the effects of single nucleotide polymorphisms (SNPs) in the abovementioned genes. Because of their metabolic function, folate and other one-carbon micronutrients may be important factors in the control of uracil misincorporation.

Associations between single nucleotide polymorphisms in folate uptake and metabolizing genes with blood folate, homocysteine, and DNA uracil concentrations.

Background: Folate is an essential nutrient that supports nucleotide synthesis and biological methylation reactions. Diminished folate status results in chromosome breakage and is associated with several diseases, including colorectal cancer. Folate status is also inversely related to plasma homocysteine concentrations -- a risk factor for cardiovascular disease.

Preferential response of glutathione-related enzymes to folate-dependent changes in the redox state of rat liver.

Background: Oxidative stress likely constitutes an important contributing factor in the onset of degenerative diseases associated with folate deficiency. Direct, as well as homocysteine-linked, antioxidant properties of folate could explain its preventive effect on these pathologies.

Aim Of The Study: Our study aimed at determining the changes in the redox status of adult rats as a function of folate intake.

Proteomic analysis reveals changes in the liver protein pattern of rats exposed to dietary folate deficiency.

Epidemiologic and experimental studies showed that folate deficiency is associated with increased risk of degenerative diseases by enhancing abnormal one-carbon metabolism. We studied the changes in the proteome of liver, the main tissue of folate storage and metabolism, in a rat model of dietary folate depletion. Four-month-old rats were fed for 4 wk an amino acid-defined diet without folate and compared with pair-fed rats given the same diet adequately supplemented with folic acid.

Evaluation of magnesium fluxes in rat erythrocytes using a stable isotope of magnesium.

The mechanisms that maintain intracellular Mg concentration at physiologic levels are not fully understood. In this work, we described for the first time, a new method using 25Mg stable isotopes, that allows simultaneous determination of Mg2+ efflux and Mg2+ influx in non-loaded cells at physiological levels of extracellular Mg. Erythrocytes from rats were suspended as a 10% suspension in NaCl medium or choline medium.

Age-associated B vitamin deficiency as a determinant of chronic diseases.

The number of elderly individuals is growing rapidly worldwide and degenerative diseases constitute an increasing problem in terms of both public health and cost. Nutrition plays a role in the ageing process and there has been intensive research during the last decade on B vitamin-related risk factors in vascular and neurological diseases and cancers. Data from epidemiological studies indicate that subclinical deficiency in most water-soluble B vitamins may occur gradually during ageing, possibly due to environmental, metabolic, genetic, nutritional and pathological determinants, as well as to lifestyle, gender and drug consumption.