The impact of <Emphasis Type="Italic">MTHFR</Emphasis> 677C → T risk knowledge on changes in folate intake: findings from the Food4Me study

Background

It is hypothesised that individuals with knowledge of their genetic risk are more likely to make health-promoting dietary and lifestyle changes. The present study aims to test this hypothesis using data from the Food4Me study. This was a 6-month Internet-based randomised controlled trial conducted across seven centres in Europe where individuals received either general healthy eating advice or varying levels of personalised nutrition advice. Participants who received genotype-based personalised advice were informed whether they had the risk (CT/TT) (n?=?178) or non-risk (CC) (n?=?141) alleles of the methylenetetrahydrofolate reductase (MTHFR) gene in relation to cardiovascular health and the importance of a sufficient intake of folate. General linear model analysis was used to assess changes in folate intake between the MTHFR risk, MTHFR non-risk and control groups from baseline to month 6 of the intervention.

Results

There were no differences between the groups for age, gender or BMI. However, there was a significant difference in country distribution between the groups (p?=?0.010). Baseline folate intakes were 412?±?172, 391?±?190 and 410?±?186 μg per 10 MJ for the risk, non-risk and control groups, respectively. There were no significant differences between the three groups in terms of changes in folate intakes from baseline to month 6. Similarly, there were no changes in reported intake of food groups high in folate.

Conclusions

These results suggest that knowledge of MTHFR 677C?→?T genotype did not improve folate intake in participants with the risk variant compared with those with the non-risk variant.

Trial registration

ClinicalTrials.gov NCT01530139

     

Effect of Dietary Patterns on Muscle Strength and Physical Performance in the Very Old: Findings from the Newcastle 85+ Study

Background

Healthy diet has been associated with better muscle strength and physical performance in cross-sectional studies of older adults but the effect of dietary patterns (DP) on subsequent decline, particularly in the very old (aged 85+), has not been determined.

Objective

We investigated the association between previously established DP and decline in muscle strength and physical performance in the very old.

Design

791 participants (61.8% women) from the Newcastle 85+ Study were followed-up for change in hand grip strength (HGS) and Timed Up-and Go (TUG) test over 5 years (four waves 1.5 years apart). Mixed models were used to determine the effects of DP on muscle strength and physical performance in the entire cohort and separately by sex.

Results

Previously we have established three DP that varied in intake of red meats, potato, gravy and butter and differed with key health and social factors. HGS declined linearly by 1.59 kg_F in men and 1.08 kg_F in women (both p<0.001), and TUG slowed by 0.13 log₁₀-transformed seconds (log₁₀-s) in men and 0.11 log₁₀-s in women per wave after adjusting for important covariates (both p<0.001), and also showed a nonlinear change (p<0.001). Men in DP1 (‘High Red Meat’) had worse overall HGS (β = -1.70, p = 0.05), but men in DP3 (‘High Butter’) had a steeper decline (β = -0.63, p = 0.05) than men in DP2 (‘Low Meat’). Men in DP1 and women in DP3 also had overall slower TUG than those in DP2 (β = 0.08, p = 0.001 and β = 0.06, p = 0.01, respectively), but similar rate of decline after adjusting for sociodemographic, lifestyle, health, and functioning factors. The results for HGS and TUG were not affected by participants’ cognitive status.

Conclusions

DP high in red meats, potato and gravy (DP1), or butter (DP3) may adversely affect muscle strength and physical performance in later life, independently of important covariates and cognitive status.     

Negative feedback regulation of FGF signaling levels by Pyst1/MKP3 in chick embryos

BACKGROUND: The importance of endogenous antagonists in intracellular signal transduction pathways is becoming increasingly recognized. There is evidence in cultured mammalian cells that Pyst1/MKP3, a dual specificity protein phosphatase, specifically binds to and inactivates ERK1/2 mitogen-activated protein kinases (MAPKs). High-level Pyst1/Mkp3 expression has recently been found at many sites of known FGF signaling in mouse embryos, but the significance of this association and its function are not known. RESULTS: We have cloned chicken Pyst1/Mkp3 and show that high-level expression in neural plate correlates with active MAPK. We show that FGF signaling regulates Pyst1 expression in developing neural plate and limb bud by ablating and/or transplanting tissue sources of FGFs and by applying FGF protein or a specific FGFR inhibitor (SU5402). We further show by applying a specific MAP kinase kinase inhibitor (PD184352) that Pyst1 expression is regulated via the MAPK cascade. Overexpression of Pyst1 in chick embryos reduces levels of activated MAPK in neural plate and alters its morphology and retards limb bud outgrowth. CONCLUSIONS: Pyst1 is an inducible antagonist of FGF signaling in embryos and acts in a negative feedback loop to regulate the activity of MAPK. Our results demonstrate both the importance of MAPK signaling in neural induction and limb bud outgrowth and the critical role played by dual specificity MAP kinase phosphatases in regulating developmental outcomes in vertebrates.     

定向进化人α型干扰素基因家族的研究

应用DNA改组(DNAshuffling)技术重组了12种人α型干扰素基因,并结合噬菌体表面呈现(phagedisplay)技术构建了噬菌体干扰素改组文库,采用简便的、功能性的定向竞争筛选方法,获得了比活达1 0×109IU/mg的新型α型基因工程复合干扰素,是目前国际上已投产的α2型干扰素的5倍,具有生产应用前景,上述策略也为其它细胞因子或酶的改造提供了借鉴方法。     

Spontaneous and GABA-induced single channel currents in cultured murine spinal cord neurons

Intracellular and patch clamp recordings were made from embryonic mouse spinal cord neurons growing in primary cell culture. Outside-out membrane patches obtained from these cells usually showed spontaneous single channel currents when studied at the resting potential (-56 +/- 1.5 mV). In 18 out of 30 patches tested, spontaneous single channel activity was abolished by making Tris+ the major cation on both sides of the membrane. The remaining patches continued to display spontaneous single channel currents under these conditions. These events reversed polarity at a patch potential of 0 mV and displayed a mean single channel conductance of 24 +/- 1.2 pS. Application of the putative inhibitory transmitter gamma-aminobutyric acid (0.5-10 microM) to outside-out patches of spinal cord cell membrane induced single channel currents in 10 out of 15 patches tested. These channels had a primary conductance of 29 +/- 2.8 pS in symmetrical 145 mM Cl- solutions. Frequency distributions for the open times of these channels were well fit by the sum of a fast exponential term ("of") with a time constant tau of = 4 +/- 1.3 ms and a slow exponential term ("os") with a time constant tau os = 24 +/- 8.1 ms. Frequency distributions for channel closed times were also well fit by a double exponential equation, with time constants tau cf = 2 +/- 0.2 ms and tau cs = 62 +/- 20.9 ms.     

Folate intake and bowel cancer risk

Folate is a B vitamin required for one-carbon transfer reactions including methylation of cell macromolecules including DNA and synthesis of the purines adenosine and guanosine and the pyrimidine thymidine. Epidemiological evidence suggests that diets providing higher amounts of folates lower the risk of colo-rectal cancer (CRC) and these observations are supported by plausible biological mechanisms. Inadequate folate supply results in DNA damage through (a) the incorporation of uracil (in place of thymidine) into DNA and subsequent unsuccessful attempts at DNA repair and (b) aberrant patterns of DNA methylation. However, human intervention studies using relatively large doses (500–5,000 μg/day) of folic acid (a synthetic form of folate) have provided no evidence of benefit in terms of adenoma recurrence. Indeed, there is some evidence of potential harm in increased risk of prostate cancer. Possible reasons for the apparent divergence in findings from the observational and intervention studies include the use of (unphysiologically) large doses of folic acid in the intervention studies whereas smaller intakes of food folates appeared to offer “protection” against CRC in case–control and prospective cohort studies. With intakes of folic acid greater than 400 μg/day, unmetabolised folic acid appears in peripheral blood and there are suggestions that this folic acid may have adverse effects e.g. reduced cytotoxicity of Natural Killer cells. Until the benefit-risk relationship associated with mandatory fortification with folic acid has been clarified (and, in particular, the possible risk of inducing extra cases of bowel or other cancer), it would seem wise to delay further mandatory folic acid fortification.     

Phosphoglucose isomerase and esterase phenotypes in Crassostrea angulata and C. gigas

The phenotype distributions and the allele frequencies of the phosphoglucose isomerase and esterase loci examined in the samples of Crassostrea angulata (Essex, England) and C. gigas (Brittany) do not differ significantly and the two populations as such are indistinguishable. The validity of the species C. angulata is questioned and it is postulated that the two samples may be geographic isolates of the same species, i.e. C. gigas. The hatchery reared population of C. gigas from Conway is distinguishable from the other samples of Crassostrea examined. The lack of phenotype diversity is attributed to founder effects of the small parental stock imported in 1965. The distributions of all phenotypes are in agreement with Hardy-Weinberg expectations. Phosphoglucose isomerase (E.C. 5.3.1.9.) is a dimer governed by at least four alleles in C. angulata and five alleles in C. gigas. The slower (Es-S) zone of the esterase electrophoretogram would appear, in both species to be governed by four alleles at a single locus. There was no esterase banding which was specific to either species of Crassostrea.