The expression of ferritin, lactoferrin, transferrin receptor and solute carrier family 11A1 in the host response to BCG-vaccination and Mycobacterium tuberculosis challenge

Iron is an essential cofactor for both mycobacterial growth during infection and for a successful protective immune response by the host. The immune response partly depends on the regulation of iron by the host, including the tight control of expression of the iron-storage protein, ferritin. BCG vaccination can protect against disease following Mycobacterium tuberculosis infection, but the mechanisms of protection remain unclear. To further explore these mechanisms, splenocytes from BCG-vaccinated guinea pigs were stimulated ex vivo with purified protein derivative from M. tuberculosis and a significant down-regulation of ferritin light- and heavy-chain was measured by reverse-transcription quantitative-PCR (P ≤0.05 and ≤0.01, respectively). The mechanisms of this down-regulation were shown to involve TNFα and nitric oxide. A more in depth analysis of the mRNA expression profiles, including genes involved in iron metabolism, was performed using a guinea pig specific immunological microarray following ex vivo infection with M. tuberculosis of splenocytes from BCG-vaccinated and naïve guinea pigs. M. tuberculosis infection induced a pro-inflammatory response in splenocytes from both groups, resulting in down-regulation of ferritin (P ≤0.05). In addition, lactoferrin (P ≤0.002), transferrin receptor (P ≤0.05) and solute carrier family 11A1 (P ≤0.05), were only significantly down-regulated after infection of the splenocytes from BCG-vaccinated animals. The results show that expression of iron-metabolism genes is tightly regulated as part of the host response to M. tuberculosis infection and that BCG-vaccination enhances the ability of the host to mount an iron-restriction response which may in turn help to combat invasion by mycobacteria.

Effective separation of the actinides Am(III) and Cm(III) by electronic modulation of bis-(1,2,4-triazin-3-yl)phenanthrolines

It has been shown that modification of the phenanthroline backbone of CyMe4-BTPhen leads to subtle electronic modulation, permitting differential ligation of Am(III) and Cm(III) resulting in separation factors up to 7.

A SNP-based consensus genetic map for synteny-based trait targeting in faba bean (Vicia faba L.)

Faba bean (Vicia faba L.) is a globally important nitrogen-fixing legume, which is widely grown in a diverse range of environments. In this work, we mine and validate a set of 845 SNPs from the aligned transcriptomes of two contrasting inbred lines. Each V. faba SNP is assigned by BLAST analysis to a single Medicago orthologue. This set of syntenically anchored polymorphisms were then validated as individual KASP assays, classified according to their informativeness and performance on a panel of 37 inbred lines, and the best performing 757 markers used to genotype six mapping populations. The six resulting linkage maps were merged into a single consensus map on which 687 SNPs were placed on six linkage groups, each presumed to correspond to one of the six V. faba chromosomes. This sequence-based consensus map was used to explore synteny with the most closely-related crop species, lentil, and the most closely related fully sequenced genome, Medicago. Large tracts of uninterrupted colinearity were found between faba bean and Medicago, making it relatively straightforward to predict gene content and order in mapped genetic interval. As a demonstration of this, we mapped a flower colour gene to a 2 cM interval of Vf chromosome 2 which was highly collinear with Mt3. The obvious candidate gene from 77 gene models in the collinear Medicago chromosome segment was the previously characterized MtWD40-1 gene (Mt3g092830, Mt3g092840) controlling anthocyanin production in Medicago and re-sequencing of the Vf orthologue showed a putative causative deletion of the entire 5’ end of the gene.

Associations between FTO genotype and total energy and macronutrients intake: a systematic review and meta-analysis

Risk variants of the fat-mass and obesity-associated (FTO) gene have been associated with increased obesity. However, the evidence for associations between FTO genotype and macronutrients intake has not been reviewed systematically. Our aim was to evaluate potential associations between FTO genotype and intakes of total energy, fat, carbohydrate and protein. We undertook a systematic literature search in Medline, Scopus, EMBASE and Cochrane of associations between macronutrients intake and FTO genotype in adults. Beta coefficients and confidence intervals were used for per-allele comparisons. Random-effects models assessed the pooled effect sizes. We identified 56 eligible studies reporting on 213 173 adults. For each copy of the FTO risk allele, individuals reported 6.46 kcal/day (95% CI: 10.76, 2.16) lower total energy intake (P=0.003). Total fat (P=0.028) and protein (P=0.006), but not carbohydrate intakes, were higher in those carrying the FTO risk allele. After adjustment for body weight, total energy intakes remained significantly lower in individuals with the FTO risk genotype (P=0.028). The FTO risk allele is associated with a lower reported total energy intake and with altered patterns of macronutrients intake. Although significant, these differences are small and further research is needed to determine whether the associations are independent of dietary misreporting.

Interaction between BMI and APOE genotype is associated with changes in the plasma long-chain-PUFA response to a fish-oil supplement in healthy participants

BACKGROUND: Carriers of the apolipoprotein E ɛ4 (APOE4) allele are lower responders to a docosahexaenoic acid (DHA) supplement than are noncarriers. This effect could be exacerbated in overweight individuals because DHA metabolism changes according to body mass index (BMI; in kg/m²). OBJECTIVES: We evaluated the plasma fatty acid (FA) response to a DHA-rich supplement in APOE4 carriers and noncarriers consuming a high-saturated fat diet (HSF diet) and, in addition, evaluated whether being overweight changed this response. DESIGN: This study was part of the SATgenɛ trial. Forty-one APOE4 carriers and 41 noncarriers were prospectively recruited and consumed an HSF diet for 8-wk followed by 8 wk of consumption of an HSF diet with the addition of DHA and eicosapentaenoic acid (EPA) (HSF + DHA diet; 3.45 g DHA/d and 0.5 g EPA/d). Fasting plasma samples were collected at the end of each intervention diet. Plasma total lipids (TLs) were separated into free FAs, neutral lipids (NLs), and phospholipids by using solid-phase extraction, and FA profiles in each lipid class were quantified by using gas chromatography. RESULTS: Because the plasma FA response to the HSF + DHA diet was correlated with BMI in APOE4 carriers but not in noncarriers, the following 2 groups were formed according to the BMI median: low BMI (<25.5) and high BMI (≥25.5). In response to the HSF + DHA diet, there were significant BMI × genotype interactions for changes in plasma concentrations of arachidonic acid and DHA in phospholipids and TLs and of EPA in NLs and TLs (P ≤ 0.05). APOE4 carriers were lower plasma responders to the DHA supplement than were noncarriers but only in the high-BMI group. CONCLUSIONS: Our findings indicate that apolipoprotein E genotype and BMI may be important variables that determine the plasma long-chain PUFA response to dietary fat manipulation. APOE4 carriers with BMI ≥25.5 may need higher intakes of DHA for cardiovascular or other health benefits than do noncarriers

Transcendental Brauer groups of products of CM elliptic curves

Let L be a number field and let E/L be an elliptic curve with complex multiplication by the ring of integers O_K of an imaginary quadratic field K. We use class field theory and results of Skorobogatov and Zarhin to compute the transcendental part of the Brauer group of the abelian surface ExE. The results for the odd order torsion also apply to the Brauer group of the K3 surface Kum(ExE). We describe explicitly the elliptic curves E/Q with complex multiplication by O_K such that the Brauer group of ExE contains a transcendental element of odd order. We show that such an element gives rise to a Brauer-Manin obstruction to weak approximation on Kum(ExE), while there is no obstruction coming from the algebraic part of the Brauer group.

Interaction between FTO gene variants and lifestyle factors on metabolic traits in an Asian Indian population

Background Lifestyle factors such as diet and physical activity have been shown to modify the association between fat mass and obesity–associated (FTO) gene variants and metabolic traits in several populations; however, there are no gene-lifestyle interaction studies, to date, among Asian Indians living in India. In this study, we examined whether dietary factors and physical activity modified the association between two FTO single nucleotide polymorphisms (rs8050136 and rs11076023) (SNPs) and obesity traits and type 2 diabetes (T2D). Methods The study included 734 unrelated T2D and 884 normal glucose-tolerant (NGT) participants randomly selected from the urban component of the Chennai Urban Rural Epidemiology Study (CURES). Dietary intakes were assessed using a validated interviewer administered semi-quantitative food frequency questionnaire (FFQ). Physical activity was based upon the self-report. Interaction analyses were performed by including the interaction terms in the linear/logistic regression model. Results There was a significant interaction between SNP rs8050136 and carbohydrate intake (% energy) (Pinteraction = 0.04), where the ‘A’ allele carriers had 2.46 times increased risk of obesity than those with ‘CC’ genotype (P = 3.0 × 10−5) among individuals in the highest tertile of carbohydrate intake (% energy, 71 %). A significant interaction was also observed between SNP rs11076023 and dietary fibre intake (Pinteraction = 0.0008), where individuals with AA genotype who are in the 3rd tertile of dietary fibre intake had 1.62 cm lower waist circumference than those with ‘T’ allele carriers (P = 0.02). Furthermore, among those who were physically inactive, the ‘A’ allele carriers of the SNP rs8050136 had 1.89 times increased risk of obesity than those with ‘CC’ genotype (P = 4.0 × 10−5). Conclusions This is the first study to provide evidence for a gene-diet and gene-physical activity interaction on obesity and T2D in an Asian Indian population. Our findings suggest that the association between FTO SNPs and obesity might be influenced by carbohydrate and dietary fibre intake and physical inactivity. Further understanding of how FTO gene influences obesity and T2D through dietary and exercise interventions is warranted to advance the development of behavioral intervention and personalised lifestyle strategies, which could reduce the risk of metabolic diseases in this Asian Indian population.