Nutrient gene interactions in lipid metabolism

Purpose of review To summarize recent findings relating to the impact of dietary fat composition on whole body lipid metabolism, and common gene variants on the blood lipid response to dietary fat change. Recent findings In recent years a more comprehensive understanding of the impact of polyunsaturated fat (PUFA) intake on the regulation of transcription factors involved in lipogenesis and fatty acid and lipoprotein metabolism has emerged. The evidence is suggestive of a greater potency of the long chain n-3 PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and in particular their oxidative products, relative to n-6 Pi In the area of nutrigenetics a number of common gene variants have been identified which may be important determinants of the blood lipid response to altered dietary fat composition. However, confirmation of associations in independent cohorts, and an understanding of the size effect of individual or combinations of genotypes, is often lacking. Summary Although in the future, genotyping holds the potential as a public health tool to target and personalize dietary advice, nutrigenetics is a relatively new science, and further research is needed to address the existing inconsistencies and knowledge gaps.

Antitumor activity of Titanocene Y in xenografted PC3 tumors in mice

Chemotherapeutic options for androgen-independent prostate cancer are extremely limited with minimum survival advantage. The benzyl-substituted unbridged titanocene bis-[(p-methoxybenzyl) cyclopentadienyl] titanium(IV) dichloride (Titanocene Y) was tested in vitro against the human prostate cancer androgen-independent cell, PC-3, which demonstrated an IC50 value of 56 x 10(-6) mol/L compared to 5.6 x 10(-6) mol/L for cisplatin. Then Titanocene Y was given at the maximum tolerable dose of 40 mg/kg/d on five consecutive days to one cohort of eight PC3 tumor-bearing male NMRI: nu/nu mice, while a second cohort was treated similarly with 3 mg/kg/d of cisplatin. Both of these mouse cohorts showed a statistically significant tumor growth reduction with respect to the third solvent-treated control group, which led to T/C values of 42% for cisplatin and 52% for Titanocene Y at the end of the experiment. This encouraging activity of Titanocene Y against prostate tumors in vivo, which is almost comparable with respect to cisplatin hopefully leads to further development of Titanocene Y in the future.

A model for self-directed problem-based learning for renal therapeutics

Objective To introduce a new approach to problem-based learning (PBL) for self-directed learning in renal therapeutics. Design This 5-week course, designed for large student cohorts using minimal teaching resources, was based on a series of case studies and subsequent pharmaceutical care plans, followed by intensive and regular feedback from the instructor. Assessment Assessment of achievement of the learning outcomes was based on weekly-graded care plans and peer review assessment, allowing each student to judge the contributions of each group member and their own, along with a written case-study based examination. The pharmaceutical care plan template, designed using a “tick-box” system, significantly reduced staff time for feedback and scoring. Conclusion The proposed instructional model achieved the desired learning outcomes with appropriate student feedback, while promoting skills that are essential for the students' future careers as health care professionals.

‘Anything can happen in the next half-hour’: Gerry Anderson’s transnational science fiction

Gerry Anderson’s 1960s puppet series have hybrid identities in relation to their medial, geographical, and production histories. This chapter ranges over his science fiction series from Supercar (1961) to Joe 90 (1968), arguing that Anderson’s television science fiction in that period crossed many kinds of boundary and border. Anderson’s television series were a compromise between his desire to make films for adults versus an available market for children’s television puppet programs, and aimed to appeal to a cross-generational family audience. They were made on film, using novel effects, for a UK television production culture that still relied largely on live and videotaped production. While commissioned by British ITV companies, the programs had notable success in the USA, achieving national networked screening as well as syndication, and they were designed to be transatlantic products. The transnational hero teams and security organisations featured in the series supported this internationalism, and simultaneously negotiated between the cultural meanings of Britishness and Americanness. By discussing their means of production, the aesthetic and narrative features of the programs, their institutional contexts, and their international distribution, this chapter argues that Anderson’s series suggest ways of rethinking the boundaries of British science fiction television in the 1960s.

An evaluation of the UK Food Standards Agency's salt campaign

Excessive salt intake is linked to cardiovascular disease and several other health problems around the world. The UK Food Standards Agency initiated a campaign at the end of 2004 to reduce salt intake in the population. There is disagreement over whether the campaign was effective in curbing salt intake or not. We provide fresh evidence on the impact of the campaign, by using data on spot urinary sodium readings and socio-demographic variables from the Health Survey for England over 2003–2007 and combining it with food price information from the Expenditure and Food Survey. Aggregating the data into a pseudo-panel, we estimate fixed effects models to examine the trend in salt intake over the period and to deduce the heterogeneous effects of the policy on the intake of socio-demographic groups. Our results are consistent with a previous hypothesis that the campaign reduced salt intakes by approximately 10%. The impact is shown to be stronger among women than among men. Older cohorts of men show a larger response to the salt campaign compared to younger cohorts, while among women, younger cohorts respond more strongly than older cohorts.

Statistical monitoring of student performance: an early warning system

Weekly monitoring of profiles of student performances on formative and summative coursework throughout the year can be used to quickly identify those who need additional help, possibly due to acute and sudden-onset problems. Such an early-warning system can help retention, but also assist students in overcoming problems early on, thus helping them fulfil their potential in the long run. We have developed a simple approach for the automatic monitoring of student mark profiles for individual modules, which we intend to trial in the near future. Its ease of implementation means that it can be used for very large cohorts with little additional effort when marks are already collected and recorded on a spreadsheet.

Dietary intakes and food sources of phytoestrogens in the European Prospective Investigation into Cancer and Nutrition (EPIC) 24-hour dietary recall cohort

BACKGROUND/OBJECTIVES: Phytoestrogens are estradiol-like natural compounds found in plants that have been associated with protective effects against chronic diseases, including some cancers, cardiovascular diseases and osteoporosis. The purpose of this study was to estimate the dietary intake of phytoestrogens, identify their food sources and their association with lifestyle factors in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. SUBJECTS/METHODS: Single 24-hour dietary recalls were collected from 36 037 individuals from 10 European countries, aged 35–74 years using a standardized computerized interview programe (EPIC-Soft). An ad hoc food composition database on phytoestrogens (isoflavones, lignans, coumestans, enterolignans and equol) was compiled using data from available databases, in order to obtain and describe phytoestrogen intakes and their food sources across 27 redefined EPIC centres. RESULTS: Mean total phytoestrogen intake was the highest in the UK health-conscious group (24.9 mg/day in men and 21.1 mg/day in women) whereas lowest in Greece (1.3 mg/day) in men and Spain-Granada (1.0 mg/day) in women. Northern European countries had higher intakes than southern countries. The main phytoestrogen contributors were isoflavones in both UK centres and lignans in the other EPIC cohorts. Age, body mass index, educational level, smoking status and physical activity were related to increased intakes of lignans, enterolignans and equol, but not to total phytoestrogen, isoflavone or coumestan intakes. In the UK cohorts, the major food sources of phytoestrogens were soy products. In the other EPIC cohorts the dietary sources were more distributed, among fruits, vegetables, soy products, cereal products, non-alcoholic and alcoholic beverages. CONCLUSIONS: There was a high variability in the dietary intake of total and phytoestrogen subclasses and their food sources across European regions.

Children of the revolution: fathers and sons in antifascist DEFA films

The article looks at three antifascist films from the 1980s by the East German film company DEFA: Jürgen Brauer's Pugowitza (1981), Egon Schlegel's Die Schüsse der Arche Noah (1983), and Helmut Dziuba's Jan auf der Zille (1986), which during this final decade of the East German state re-examine an ideologically seminal constellation of the GDR's official antifascism – the relationship between antifascist father and son. Linking generational and political succession, the father-son relationship helped to legitimise the GDR as a state in which the young continued the antifascist fight of the old communists against the Nazi dictatorship. From the 1950s on, DEFA films contributed to the visualisation of this relationship, codifying it not only as heroic but also as ‘natural’: the assumed innocence of the communist son was meant to naturalise the father's antifascist/communist cause. The 1980s saw this naturalised political succession questioned. By re-telling the canonised father-son story, the three films visualise the generational antifascist contract as flawed. Re-deploying the son's assumed innocence in a critique of the father, they explore new endings to the antifascist story and revive the discussion of categories like ‘victim’ and ‘perpetrator’.// Der Aufsatz untersucht drei antifaschistische Filme der ostdeutschen Filmgesellschaft DEFA aus den 1980er Jahren: Jürgen Brauers Pugowitza (1981), Egon Schlegels Die Schüsse der Arche Noah (1983) und Helmut Dziubas Jan auf der Zille (1986). Alle drei Filme wurden im letzten Jahrzehnt der DDR gedreht und greifen eine ideologisch tragende Konstellation des offiziellen DDR-Antifaschismus auf – die Beziehung zwischen antifaschistischem Vater und Sohn. In der Vater-Sohn-Beziehung verband sich Generationenabfolge mit politischer Nachkommenschaft, eine Verbindung, die half, die DDR als einen Staat zu legitimieren, in dem die Jungen den antifaschistischen Kampf der alten Kommunisten gegen die Nazi-Diktatur weiterführten. Seit den 1950er Jahren beteiligte sich die DEFA an der Visuali-sierung dieser Beziehung und kodifizierte sie nicht nur als heldenhaft, sondern auch als ‘natürlich’: die behauptete Unschuld der kommunistschen Söhne diente dazu, den antifaschistisch-kommunistischen Kampf der Väter zu naturalisieren. Die solcher Art politisch interpretierte Generationenabfolge verlor ihre Natürlichkeit, als sie in den 1980er Jahren kritisch befragt wurde. Im nochmaligen Erzählen der kanonisierten Vater-Sohn-Geschichte wird die Brüchigkeit des antifaschistischen Gesellschaftsvertrags in allen drei Filmen sichtbar. Die vermeintliche Unschuld der Söhne wird nun zu einer Kritik der Väter genutzt, wobei die Filme ein neues Ende für die antifaschistische Geschichte erkunden und die Debatte über Kategorien wie ‘Opfer’ und ‘Täter’ wieder aufnehmen.

Thinking out of the box – skills for work

Since the Dearing Report .1 there has been an increased emphasis on the development of employability and transferable (‘soft’) skills in undergraduate programmes. Within STEM subject areas, recent reports concluded that universities should offer ‘greater and more sustainable variety in modes of study to meet the changing demands of industry and students’.2 At the same time, higher education (HE) institutions are increasingly conscious of the sensitivity of league table positions on employment statistics and graduate destinations. Modules that are either credit or non-credit bearing are finding their way into the core curriculum at HE. While the UK government and other educational bodies argue the way forward over A-level reform, universities must also meet the needs of their first year cohorts in terms of the secondary to tertiary transition and developing independence in learning.

Circulating insulin-like factor 3 (INSL3) in healthy and infertile women

STUDY QUESTION: How does insulin-like factor 3 (INSL3) concentration in blood vary across the menstrual cycle in women? SUMMARY ANSWER: INSL3 is secreted by the theca interna cells of growing antral follicles and is phasic in its expression. WHAT IS KNOWN ALREADY: The relaxin-like hormone INSL3 is known to be expressed in follicles of several mammal species, and was recently shown in cows to be specifically secreted into the bloodstream by growing antral follicles, corresponding to follicular waves. In males INSL3 is known to be acutely independent of the hormones of the hypothalamic-pituitary-gonadal axis, suggesting that in women INSL3 might be a novel biomarker for antral follicle recruitment and development. STUDY DESIGN, SIZE, DURATION: Two cohorts of women were studied. First, 18 healthy women of reproductive age were followed longitudinally for one and a half cycles, with blood sampling and hormone measurement every 2-3 days. A second cohort comprised a cross-sectional study of 909 women attending an infertility clinic, with a single blood sample taken at entry, together with other clinical and hormonal parameters. PARTICIPANTS/MATERIALS, SETTING, METHODS: Blood samples from both retrospective cohorts were analyzed for INSL3 using a highly sensitive time-resolved fluorescent immunoassay, and data were analyzed in comparison with other clinical and hormonal parameters. MAIN RESULT AND THE ROLE OF CHANCE: For young healthy women of reproductive age, we showed a phasic expression of INSL3 corresponding to antral follicle growth in both the follicular and luteal phases of the cycle, which was significantly (P < 0.05) elevated compared with that during menses. For women attending an infertility clinic, those with diagnosed polycystic ovarian syndrome indicated significantly (P < 0.0005) greater circulating INSL3 levels and those with low ovarian reserve showed significantly (P < 0.002) decreased INSL3 values. LIMITATIONS, REASONS FOR CAUTION: These were retrospective studies and the results were obtained from natural cycles only, with their inherent variability. WIDER IMPLICATIONS OF THE FINDINGS: We show for the first time that INSL3 in women does vary across the menstrual cycle, and appears to reflect the number of growing antral follicles recruited within both follicular and luteal phases. STUDY FUNDING/COMPETING INTEREST(S): The present retrospective study was largely supported by departmental funds. There were no competing interests.

Influence of dietary protein intake and glycemic index on the association between TCF7L2 HapA and weight gain

BACKGROUND: Genetic polymorphisms of transcription factor 7-like 2 (TCF7L2) have been associated with type 2 diabetes and BMI. OBJECTIVE: The objective was to investigate whether TCF7L2 HapA is associated with weight development and whether such an association is modulated by protein intake or by the glycemic index (GI). DESIGN: The investigation was based on prospective data from 5 cohort studies nested within the European Prospective Investigation into Cancer and Nutrition. Weight change was followed up for a mean (±SD) of 6.8 ± 2.5 y. TCF7L2 rs7903146 and rs10885406 were successfully genotyped in 11,069 individuals and used to derive HapA. Multiple logistic and linear regression analysis was applied to test for the main effect of HapA and its interaction with dietary protein or GI. Analyses from the cohorts were combined by random-effects meta-analysis. RESULTS: HapA was associated neither with baseline BMI (0.03 ± 0.07 BMI units per allele; P = 0.6) nor with annual weight change (8.8 ± 11.7 g/y per allele; P = 0.5). However, a previously shown positive association between intake of protein, particularly of animal origin, and subsequent weight change in this population proved to be attenuated by TCF7L2 HapA (P-interaction = 0.01). We showed that weight gain becomes independent of protein intake with an increasing number of HapA alleles. Substitution of protein with either fat or carbohydrates showed the same effects. No interaction with GI was observed. CONCLUSION: TCF7L2 HapA attenuates the positive association between animal protein intake and long-term body weight change in middle-aged Europeans but does not interact with the GI of the diet.

A genome-wide association meta-analysis identifies new childhood obesity loci

Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of 14 studies consisting of 5,530 cases (≥95th percentile of body mass index (BMI)) and 8,318 controls (<50th percentile of BMI) of European ancestry. Taking forward the eight newly discovered signals yielding association with P < 5 × 10(-6) in nine independent data sets (2,818 cases and 4,083 controls), we observed two loci that yielded genome-wide significant combined P values near OLFM4 at 13q14 (rs9568856; P = 1.82 × 10(-9); odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 × 10(-9); OR = 1.14). Both loci continued to show association when two extreme childhood obesity cohorts were included (2,214 cases and 2,674 controls). These two loci also yielded directionally consistent associations in a previous meta-analysis of adult BMI(1).

Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

The Gly482Ser genotype at the PPARGC1A gene and elevated blood pressure: a meta-analysis involving 13,949 individuals.

The protein encoded by the PPARGC1A gene is expressed at high levels in metabolically active tissues and is involved in the control of oxidative stress via reactive oxygen species detoxification. Several recent reports suggest that the PPARGC1A Gly482Ser (rs8192678) missense polymorphism may relate inversely with blood pressure. We used conventional meta-analysis methods to assess the association between Gly482Ser and systolic (SBP) or diastolic blood pressures (DBP) or hypertension in 13,949 individuals from 17 studies, of which 6,042 were previously unpublished observations. The studies comprised cohorts of white European, Asian, and American Indian adults, and adolescents from South America. Stratified analyses were conducted to control for population stratification. Pooled genotype frequencies were 0.47 (Gly482Gly), 0.42 (Gly482Ser), and 0.11 (Ser482Ser). We found no evidence of association between Gly482Ser and SBP [Gly482Gly: mean = 131.0 mmHg, 95% confidence interval (CI) = 130.5-131.5 mmHg; Gly482Ser mean = 133.1 mmHg, 95% CI = 132.6-133.6 mmHg; Ser482Ser: mean = 133.5 mmHg, 95% CI = 132.5-134.5 mmHg; P = 0.409] or DBP (Gly482Gly: mean = 80.3 mmHg, 95% CI = 80.0-80.6 mmHg; Gly482Ser mean = 81.5 mmHg, 95% CI = 81.2-81.8 mmHg; Ser482Ser: mean = 82.1 mmHg, 95% CI = 81.5-82.7 mmHg; P = 0.651). Contrary to previous reports, we did not observe significant effect modification by sex (SBP, P = 0.966; DBP, P = 0.715). We were also unable to confirm the previously reported association between the Ser482 allele and hypertension [odds ratio: 0.97, 95% CI = 0.87-1.08, P = 0.585]. These results were materially unchanged when analyses were focused on whites only. However, statistical evidence of gene-age interaction was apparent for DBP [Gly482Gly: 73.5 (72.8, 74.2), Gly482Ser: 77.0 (76.2, 77.8), Ser482Ser: 79.1 (77.4, 80.9), P = 4.20 x 10(-12)] and SBP [Gly482Gly: 121.4 (120.4, 122.5), Gly482Ser: 125.9 (124.6, 127.1), Ser482Ser: 129.2 (126.5, 131.9), P = 7.20 x 10(-12)] in individuals <50 yr (n = 2,511); these genetic effects were absent in those older than 50 yr (n = 5,088) (SBP, P = 0.41; DBP, P = 0.51). Our findings suggest that the PPARGC1A Ser482 allele may be associated with higher blood pressure, but this is only apparent in younger adults.

Task design and second language performance: the effect of narrative type on learner output

This article presents a study examining how narrative structure and narrative complexity might influence the performance of second language learners. Forty learners of English in London and sixty learners in Teheran were asked to retell cartoon stories from picture prompts. Each performed two of four narrative tasks that had different degrees of narrative structure (loose or tight) and of storyline complexity (with or without background events). Results support the findings of previous research that tight task structure is connected to increased accuracy and that narratives involving background information give rise to more complex syntax. A comparison of the data from the London and Teheran cohorts showed that the learners in London used significantly more complex syntax and diverse vocabulary even though they did not differ from the Teheran learners in other performance dimensions.