Effect of fructose overfeeding and fish oil administration on hepatic de novo lipogenesis and insulin sensitivity in healthy men.

High-fructose diet stimulates hepatic de novo lipogenesis (DNL) and causes hypertriglyceridemia and insulin resistance in rodents. Fructose-induced insulin resistance may be secondary to alterations of lipid metabolism. In contrast, fish oil supplementation decreases triglycerides and may improve insulin resistance. Therefore, we studied the effect of high-fructose diet and fish oil on DNL and VLDL triglycerides and their impact on insulin resistance. Seven normal men were studied on four occasions: after fish oil (7.2 g/day) for 28 days; a 6-day high-fructose diet (corresponding to an extra 25% of total calories); fish oil plus high-fructose diet; and control conditions. Following each condition, fasting fractional DNL and endogenous glucose production (EGP) were evaluated using [1-13C]sodium acetate and 6,6-2H2 glucose and a two-step hyperinsulinemic-euglycemic clamp was performed to assess insulin sensitivity. High-fructose diet significantly increased fasting glycemia (7 +/- 2%), triglycerides (79 +/- 22%), fractional DNL (sixfold), and EGP (14 +/- 3%, all P < 0.05). It also impaired insulin-induced suppression of adipose tissue lipolysis and EGP (P < 0.05) but had no effect on whole- body insulin-mediated glucose disposal. Fish oil significantly decreased triglycerides (37%, P < 0.05) after high-fructose diet compared with high-fructose diet without fish oil and tended to reduce DNL but had no other significant effect. In conclusion, high-fructose diet induced dyslipidemia and hepatic and adipose tissue insulin resistance. Fish oil reversed dyslipidemia but not insulin resistance.

Human chorionic gonadotropin in pregnancy and maternal risk of breast cancer.

Full-term pregnancies are associated with long-term reductions in maternal risk of breast cancer, but the biological determinants of the protection are unknown. Experimental observations suggest that human chorionic gonadotropin (hCG), a major hormone of pregnancy, could play a role in this association. A case-control study (242 cases and 450 controls) nested within the Northern Sweden Maternity Cohort included women who had donated a blood sample during the first trimester of a first full-term pregnancy. Total hCG was determined on Immulite 2000 analyzer. Odds ratios (OR) and 95% confidence intervals (CI) were estimated through conditional logistic regression. Maternal breast cancer risk decreased with increasing hCG (upper tertile OR, 0.67; CI, 0.46-0.99), especially for pregnancies before age 25 (upper tertile OR, 0.41; CI, 0.21-0.80). The association diverged according to age at diagnosis: risk was reduced after age 40 (upper tertile OR, 0.60; CI, 0.39-0.91) and seemed to increase before age 40 (upper tertile OR, 1.78; CI, 0.72-4.38). Risk was reduced among those diagnosed 10 years or longer after blood draw (upper tertile OR, 0.60; CI, 0.40-0.90), but not so among those diagnosed within 10 years (upper tertile OR, 4.33; CI, 0.86-21.7). These observations suggest that the association between pregnancy hCG and subsequent maternal risk of breast cancer is modified by age at diagnosis. Although the hormone seems to be a determinant of the reduced risk around or after age 50, it might not confer protection against, or it could even increase the risk of, cancers diagnosed in the years immediately following pregnancy.

Perdas de solo e água por erosão hídrica influenciadas por métodos de preparo, classes de declive e níveis de fertilidade do solo

A erosão é a forma mais prejudicial de degradação do solo. Além de reduzir sua capacidade produtiva para as culturas, ela pode causar sérios danos ambientais, como assoreamento e poluição das fontes de água. Contudo, usando adequados sistemas de manejo do solo e bem planejadas práticas conservacionistas de suporte, os problemas de erosão podem ser satisfatoriamente resolvidos. Com o propósito de obter informações quantitativas sobre o assunto, para servirem de guia nos planejamentos conservacionistas de uso da terra, realizou-se um experimento de erosão sob chuva natural, em Latossolo Vermelho distroférrico típico textura muito argilosa, no município de Santo Ângelo, região das Missões (RS), de dezembro de 1994 a maio de 1996, objetivando quantificar as perdas de solo e água causadas por erosão hídrica. Os tratamentos consistiram dos métodos de preparo do solo convencional, reduzido e semeadura direta, avaliados sob as condições "solo com fertilidade corrigida" nas classes de declividade de 0-0,04; 0,04-0,08 e 0,08-0,12 m m-1 (com gradientes médios de, respectivamente, 0,035; 0,065 e 0,095 m m-1) e "solo com fertilidade atual" na classe de declividade de 0,04-0,08 m m-1. As operações de preparo do solo e semeadura foram efetuadas todas transversalmente ao declive, exceto para o tratamento-testemunha (preparo convencional, sem cultivo, continuamente descoberto e sem crosta), no qual as operações de aração e gradagem foram realizadas no sentido do declive. A seqüência de culturas utilizada na avaliação da erosão foi constituída de dois ciclos culturais de soja (Glycine max, L.), no período de primavera-verão de 1994/95 e 1995/96, e um de aveia preta (Avena strigosa, S.), no período de outono-inverno de 1995. O índice de erosividade das chuvas (EI30) calculado no período experimental (1,5 ano) foi de 10.236 MJ mm ha-1 h-1 e concentrou-se, repetidamente, em 1995 e 1996, nos meses de janeiro a março, perfazendo, acumuladamente nestes duplos períodos, 70 % do total. Perdas significativas de solo por erosão hídrica (até 80 Mg ha-1 em um único ciclo cultural) ocorreram somente no preparo convencional sem cultivo e estabelecido no sentido do declive (testemunha), embora o solo na parcela tenha apresentado um valor de erodibilidade muito baixo (fator K igual a 0,0091 Mg ha h MJ-1 mm-1 ha-1 ). Sob cultivo, porém em valores bem mais baixos, as perdas de solo continuaram sendo as maiores no preparo convencional (ao redor de 13,0 Mg ha-1 em 1,5 ano), notadamente nas classes de declividade média e alta, ficando o preparo reduzido com as intermediárias (ao redor de 4,0 Mg ha-1 em 1,5 ano) e a semeadura direta com as menores (ao redor de 1,0 Mg ha-1 em 1,5 ano), enquanto as perdas de água foram todas muito baixas e pouco diferenciadas. A condição "solo com fertilidade corrigida" aumentou muito a quantidade de fitomassa aérea produzida pelas culturas e, conseqüentemente, a massa de resíduos culturais, a percentagem de cobertura morta do solo e as perdas de solo por erosão hídrica, especialmente no preparo convencional; contudo, ela praticamente não influenciou as perdas de água. Apesar das operações de preparo do solo e semeadura em contorno, fertilidade do solo melhorada e alta resistência do solo à erosão, o sistema de produção aveia preta-soja em preparo convencional apresentou, em declives superiores a 0,04 m m-1, perdas anuais de solo por erosão muito próximas ao limite tolerável, já no curto comprimento de rampa de 21 m utilizado nas parcelas experimentais deste estudo.

Inclusive fitness theory and eusociality.

Arising from M. A. Nowak, C. E. Tarnita & E. O. Wilson 466, 1057-1062 (2010); Nowak et al. reply. Nowak et al. argue that inclusive fitness theory has been of little value in explaining the natural world, and that it has led to negligible progress in explaining the evolution of eusociality. However, we believe that their arguments are based upon a misunderstanding of evolutionary theory and a misrepresentation of the empirical literature. We will focus our comments on three general issues.

Fripon, bouffon, sot : pour une relecture de M. Bakhtine

Le philosophe et théoricien russe de la littérature Mikhaïl Bakhtine a discuté des fonctions du fripon, du bouffon et du sot dans son étude "Les formes du temps et du chronotope dans le roman". Pour Bakhtine, ces trois figures jouent un rôle important dans l'évolution du roman européen, dans la mesure où elles reflètent la démarche du romancier: plutôt que de prendre part à la vie, les fripons, bouffons et sots l'observent et la mettent à nu. Afin d'évaluer s'il s'agit toujours des mêmes concepts, ce triple paradigme est interrogé dans ce recueil à travers différentes traditions culturelles.

Interstitial dendritic cell guidance by haptotactic chemokine gradients.

Directional guidance of cells via gradients of chemokines is considered crucial for embryonic development, cancer dissemination, and immune responses. Nevertheless, the concept still lacks direct experimental confirmation in vivo. Here, we identify endogenous gradients of the chemokine CCL21 within mouse skin and show that they guide dendritic cells toward lymphatic vessels. Quantitative imaging reveals depots of CCL21 within lymphatic endothelial cells and steeply decaying gradients within the perilymphatic interstitium. These gradients match the migratory patterns of the dendritic cells, which directionally approach vessels from a distance of up to 90-micrometers. Interstitial CCL21 is immobilized to heparan sulfates, and its experimental delocalization or swamping the endogenous gradients abolishes directed migration. These findings functionally establish the concept of haptotaxis, directed migration along immobilized gradients, in tissues.

Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits.

Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5×10(-8)), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.

Black holes as fundamental strings: Comparing the absorption of scalars

The recently proposed correspondence principle of Horowitz and Polchinski provides a concrete means to relate (among others) black holes with electric Neveu-SchwarzNeveu-Schwarz charges to fundamental strings and correctly match their entropies. We further test this correspondence by examining the greybody factors in the absorption rates of neutral, minimally coupled scalars by a near extremal black hole. Perhaps surprisingly, the results disagree in general with the absorption by weakly coupled strings. Though this does not disprove the correspondence, it indicates that it might not be simple in this region of the black hole parameter space.

Physical-hydraulic properties of a sandy loam typic paleudalf soil under organic cultivation of 'montenegrina' mandarin (Citrus deliciosa Tenore)¹

Citrus plants are the most important fruit species in the world, with emphasis to oranges, mandarins and lemons. In Rio Grande do Sul, Brazil, most fruit production is found on small properties under organic cultivation. Soil compaction is one of the factors limiting production and due to the fixed row placement of this crop, compaction can arise in various manners in the interrows of the orchard. The aim of this study was to evaluate soil physical properties and water infiltration capacity in response to interrow management in an orchard of mandarin (Citrus deliciosa Tenore 'Montenegrina') under organic cultivation. Interrow management was performed through harrowing, logs in em "V", mowing, and cutting/knocking down plants with a knife roller. Soil physical properties were evaluated in the wheel tracks of the tractor (WT), between the wheel tracks (BWT), and in the area under the line projection of the canopy (CLP), with undisturbed soil samples collected in the 0.00-0.15, 0.15-0.30, 0.30-0.45, and 0.45-0.60 m layers, with four replicates. The soil water infiltration test was performed using the concentric cylinder method, with a maximum time of 90 min for each test. In general, soil analysis showed a variation in the physical-hydraulic properties of the Argissolo Vermelho-Amarelo distrófico arênico (sandy loam Typic Paleudalf) in the three sampling sites in all layers, regardless of the management procedure in the interrows. Machinery traffic leads to heterogeneity in the soil physical-hydraulic properties in the interrows of the orchard. Soil porosity and bulk density are affected especially in the wheel tracks of the tractor (WT), which causes a reduction in the constant rate of infiltration and in the accumulated infiltration of water in this sampling site. The use of the disk harrow and mower leads to greater harmful effects on the soil, which can interfere with mandarin production.

Thermogenesis and fructose metabolism in humans.

Resting metabolic rate was measured in 10 healthy volunteers (25 yr, 73 kg, 182 cm) for 1 h before and 4 h during intravenous (iv) fructose administration (20% at 50 mumol.kg-1.min-1) with (+P) or without (-P) propranolol (100 micrograms/kg, 1 microgram.kg-1.min-1) during the last 2 h. Some subjects were studied a further 2 h with fructose infusion and +P or -P in hyperinsulinemic (2.9 pmol.kg-1.min-1) euglycemic conditions. Glucose turnover ([3-3H]glucose, 20 muCi bolus and 0.2 muCi/min) was calculated over 30 min at 0, 2, 4, and 6 h. The thermic effect of iv fructose was approximately 7.5% and decreased to 4.9 +/- 0.4% (P less than 0.01) +P. During the euglycemic clamp the thermic effect was 6.2 +/- 0.9% (-P) and 5.3 +/- 0.9% (+P). Hepatic glucose production (HGP) was 11.7 mumol.kg-1.min-1 (0 h) and did not change after 2 h iv fructose (11.8 +/- 0.5 and 9.8 +/- 0.6 mumol.kg-1.min-1 -P and +P, respectively) but increased to 13.8 +/- 0.9 (-P) and 12.9 +/- 0.8 mumol.kg-1.min-1 (+P) (P less than 0.01) after 4 h. HGP was suppressed to varying degrees during the euglycemic clamp. It is concluded that 1) the greater thermic effect of fructose compared with glucose is probably due to continued gluconeogenesis (which is suppressed by glucose or glucose-insulin) and the energy cost of fructose metabolism to glucose in the liver. 2) There is a sympathetically mediated component to the thermic effect of fructose (approximately 30%) that is not mediated by elevated plasma insulin concentrations similar to those observed with iv glucose.

Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study.

The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10(-8)) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10(-8)). The top IBC association for SBP was rs2012318 (P= 6.4 × 10(-6)) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10(-6)) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity.

Medication use in pregnancy: a cross-sectional, multinational web-based study.

OBJECTIVES: Intercountry comparability between studies on medication use in pregnancy is difficult due to dissimilarities in study design and methodology. This study aimed to examine patterns and factors associated with medications use in pregnancy from a multinational perspective, with emphasis on type of medication utilised and indication for use. DESIGN: Cross-sectional, web-based study performed within the period from 1 October 2011 to 29 February 2012. Uniform collection of drug utilisation data was performed via an anonymous online questionnaire. SETTING: Multinational study in Europe (Western, Northern and Eastern), North and South America and Australia. PARTICIPANTS: Pregnant women and new mothers with children less than 1 year of age. PRIMARY AND SECONDARY OUTCOME MEASURES: Prevalence of and factors associated with medication use for acute/short-term illnesses, chronic/long-term disorders and over-the-counter (OTC) medication use. RESULTS: The study population included 9459 women, of which 81.2% reported use of at least one medication (prescribed or OTC) during pregnancy. Overall, OTC medication use occurred in 66.9% of the pregnancies, whereas 68.4% and 17% of women reported use of at least one medication for treatment of acute/short-term illnesses and chronic/long-term disorders, respectively. The extent of self-reported medicated illnesses and types of medication used by indication varied across regions, especially in relation to urinary tract infections, depression or OTC nasal sprays. Women with higher age or lower educational level, housewives or women with an unplanned pregnancy were those most often reporting use of medication for chronic/long-term disorders. Immigrant women in Western (adjusted OR (aOR): 0.55, 95% CI 0.34 to 0.87) and Northern Europe (aOR: 0.50, 95% CI 0.31 to 0.83) were less likely to report use of medication for chronic/long-term disorders during pregnancy than non-immigrants. CONCLUSIONS: In this study, the majority of women in Europe, North America, South America and Australia used at least one medication during pregnancy. There was a substantial inter-region variability in the types of medication used.