Exclusion of the Locus for Autosomal Recessive Pseudohypoaldosteronism Type 1 from the Mineralocorticoid Receptor Gene Region on Human Chromosome 4q by Linkage Analysis.

Pseudohypoaldosteronism type 1 (PHA1) is an uncommon inherited disorder characterized by salt-wasting in infancy arising from target organ unresponsiveness to mineralocorticoids. Clinical expression of the disease varies from severely affected infants who may die to apparently asymptomatic individuals. Inheritance is Mendelian and may be either autosomal dominant or autosomal recessive. A defect in the mineralocorticoid receptor has been implicated as a likely cause of PHA1. The gene for human mineralocorticoid receptor (MLR) has been cloned and physically mapped to human chromosome 4q31.1-31.2. The etiological role of MLR in autosomal recessive PHA1 was investigated by performing linkage analysis between PHA1 and three simple sequence length polymorphisms (D4S192, D4S1548, and D4S413) on chromosome 4q in 10 consanguineous families. Linkage analysis was carried out assuming autosomal recessive inheritance with full penetrance and zero phenocopy rate using the MLINK program for two-point analysis and the HOMOZ program for multipoint analysis. Lod scores of less than -2 were obtained over the whole region from D4S192 to D4S413 encompassing MLR. This provdes evidence against MLR as the site of mutations causing PHA1 in the majority of autosomal recessive families

Crossover from 2D to 3D in a weakly interacting Fermi gas

We have studied the transition from two to three dimensions in a low temperature weakly interacting $^6$Li Fermi gas. Below a critical atom number, $N_{2D}$, only the lowest transverse vibrational state of a highly anisotropic oblate trapping potential is occupied and the gas is two-dimensional. Above $N_{2D}$ the Fermi gas enters the quasi-2D regime where shell structure associated with the filling of individual transverse oscillator states is apparent. This dimensional crossover is demonstrated through measurements of the cloud size and aspect ratio versus atom number.Comment: Replaced with published manuscrip

Structurally-related (−)-epicatechin metabolites in humans: assessment using de novo chemically synthesized authentic standards

Accumulating data suggest that diets rich in flavanols and procyanidins are beneficial for human health. In this context, there has been a great interest in elucidating the systemic levels and metabolic profiles at which these compounds occur in humans. While recent progress has been made, there still exist considerable differences and various disagreements with regard to the mammalian metabolites of these compounds, which in turn is largely a consequence of the lack of availability of authentic standards that would allow for the directed development and validation of expedient analytical methodologies. In the present study, we developed a method for the analysis of structurally-related flavanol metabolites using a wide range of authentic standards. Applying this method in the context of a human dietary intervention study using comprehensively characterized and standardized flavanol- and procyanidin-containing cocoa, we were able to identify the structurally-related (−)-epicatechin metabolites (SREM) postprandially extant in the systemic circulation of humans. Our results demonstrate that (−)-epicatechin-3′-β-D-glucuronide, (−)-epicatechin-3′-sulfate, and a 3′-O-methyl(−)-epicatechin-5/7-sulfate are the predominant SREM in humans, and further confirm the relevance of the stereochemical configuration in the context of flavanol metabolism. In addition, we also identified plausible causes for the previously reported discrepancies regarding flavanol metabolism, consisting to a significant extent of inter-laboratory differences in sample preparation (enzymatic treatment and sample conditioning for HPLC analysis) and detection systems. Thus, these findings may also aid in the establishment of consensus on this topic

Estimated intake of dietary phyto-oestrogens in Australian women and evaluation of correlates of phyto-oestrogen intake.

The role of dietary phyto-oestrogens in health has been of continued interest and debate, but data available on the distribution of intake in the Australian diet are scarce. Therefore, we aimed to estimate phyto-oestrogen consumption in Australian women, describe the pattern of intake and identify correlates of high phyto-oestrogen intake. Study participants were 2078 control women (18-79 years) from two population-based case-control studies on gynaecological cancers (2002-2007). Dietary information was obtained using a 135-item FFQ, and the intakes of isoflavones, lignans, enterolignans and coumestans, including their individual components, were estimated using a database of phyto-oestrogen content in food developed in the UK. Median total intake (energy-adjusted) of phyto-oestrogens was 1·29 mg/d, including 611 µg/d isoflavones, 639 µg/d lignans, 21 µg/d enterolignans and 8 µg/d coumestrol. Both isoflavone and lignan intakes were strongly skewed towards higher values and positively correlated with age. Women consumed on average two servings of soyabean foods/week. Compared to lower phyto-oestrogen consumers (≤1·29 mg/d, median split), higher phyto-oestrogen consumers (>1·29 mg/d) were slightly older, less likely to be smokers, had a higher educational and physical activity level, lower BMI, lower intake of dietary fat, and higher intake of fibre, selected micronutrients and soyabean foods (all P < 0·03). The daily intake of phyto-oestrogens in Australian women with predominantly Caucasian ethnicity is approximately 1 mg; this is similar to other Western populations, but considerably lower than that among Asian women. However, those with a relatively high phyto-oestrogen diet seem to have a healthier lifestyle and a more favourable dietary profile compared to others

The diet-body offset in human nitrogen isotopic values: a controlled dietary study

The ‘trophic level enrichment’ between diet and body results in an overall increase in nitrogen isotopic values as the food chain is ascended. Quantifying the diet–body Δ15N spacing has proved difficult, particularly for humans. The value is usually assumed to be +3-5‰ in the archaeological literature. We report here the first (to our knowledge) data from humans on isotopically known diets, comparing dietary intake and a body tissue sample, that of red blood cells. Samples were taken from 11 subjects on controlled diets for a 30-d period, where the controlled diets were designed to match each individual’s habitual diet, thus reducing problems with short-term changes in diet causing isotopic changes in the body pool. The Δ15Ndiet-RBC was measured as +3.5‰. Using measured offsets from other studies, we estimate the human Δ15Ndiet-keratin as +5.0-5.3‰, which is in good agreement with values derived from the two other studies using individual diet records. We also estimate a value for Δ15Ndiet-collagen of ≈6‰, again in combination with measured offsets from other studies. This value is larger than usually assumed in palaeodietary studies, which suggests that the proportion of animal protein in prehistoric human diet may have often been overestimated in isotopic studies of palaeodiet

Evaluation at scale of microbiome-derived metabolites as biomarker of flavan-3-ol intake in epidemiological studies.

The accurate assessment of dietary intake is crucial to investigate the effect of diet on health. Currently used methods, relying on self-reporting and food composition data, are known to have limitations and might not be suitable to estimate the intake of many bioactive food components. An alternative are nutritional biomarkers, which can allow an unbiased assessment of intake. They require a careful evaluation of their suitability, including: (a) the availability of a precise, accurate and robust analytical method, (b) their specificity (c) a consistent relationship with actual intake. We have evaluated human metabolites of a microbiome-derived flavan-3-ol catabolite, 5-(3',4'-dihydroxyphenyl)-[gamma]-valerolactone (gVL), as biomarker of flavan-3-ol intake in large epidemiological studies. Flavan-3-ols are widely consumed plant bioactives, which have received considerable interest due to their potential ability to reduce CVD risk. The availability of authentic standards allowed the development of a validated high-throughput method suitable for large-scale studies. In dietary intervention studies, we could show that gVL metabolites are specific for flavan-3-ols present in tea, fruits, wine and cocoa-derived products, with a strong correlation between intake and biomarker (Spearman's r = 0.90). This biomarker will allow for the first time to estimate flavan-3-ol intake and further investigation of associations between intake and disease risk

5‐(3′,4′‐Dihydroxyphenyl)‐γ‐Valerolactone is a substrate for human paraoxonase: a novel pathway in flavan‐3‐ol metabolism

Scope Dietary flavan-3-ols are known to mediate cardiovascular benefits. Currently, it is assumed that the levels of flavan-3-ol catabolites detected in humans, 5-(3ʹ,4ʹ-dihydroxyphenyl)-γ-valerolactone (γVL) and 5-(3ʹ,4ʹ-dihydroxyphenyl)-γ-valeric acid (γVA), and their corresponding phase II metabolites, are determined exclusively by the action of the gut microbiome. However, a family of human proteins, paraoxonase (PON), can theoretically hydrolyze γVL metabolites into the corresponding γVAs. This study aims to determine if PON is involved in γVL and γVA metabolism in humans. Methods and results A rapid conversion of γVL into γVA is detected in serum ex vivo (half-life = 9.8 ± 0.3 min) that is catalyzed by PON1 and PON3 isoforms. Phase II metabolites of γVL are also reacted with PON in serum. Following an intake of flavan-3-ol in healthy males (n = 13), the profile of γVA metabolites detected is consistent with that predicted from the reactivity of γVL metabolites with PON in serum. Furthermore, common PON polymorphisms are evaluated to assess the use of γVL metabolites as biomarkers of flavan-3-ol intake. Conclusion PONs are involved in flavan-3-ol metabolic pathway in humans. PON polymorphisms have a minor contribution to inter-individual differences in the levels of γVL metabolites, without affecting their use as a nutritional biomarker

Female genital mutilation of a karyotypic male presenting as a female with delayed puberty

BACKGROUND: Female genital mutilation (FGM) is commonly practiced mainly in a belt reaching from East to West Africa north of the equator. The practice is known across socio-economic classes and among different ethnic, religious, and cultural groups. Few studies have been appropriately designed to measure the health effects of FGM. However, the outcome of FGM on intersex individuals has never been discussed before. CASE PRESENTATION: The patient first presented as a female with delayed puberty. Hormonal analysis revealed a normal serum prolactin level of 215 Mu/L, a low FSH of 0.5 Mu/L, and a low LH of 1.1 Mu/L. Type IV FGM (Pharaonic circumcision) had been performed during childhood. Chromosomal analysis showed a 46, XY karyotype and ultrasonography verified a soft tissue structure in the position of the prostate. CONCLUSION: FGM pose a threat to the diagnosis and management of children with abnormal genital development in the Sudan and similar societies

Evaluation of (−)-epicatechin metabolites as recovery biomarker of dietary flavan-3-ol intake

Abstract: Data from dietary intervention studies suggest that intake of (−)-epicatechin mediates beneficial vascular effects in humans. However, population-based investigations are required to evaluate associations between habitual intake and health and these studies rely on accurate estimates of intake, which nutritional biomarkers can provide. Here, we evaluate a series of structurally related (−)-epicatechin metabolites (SREM), particularly (−)-epicatechin-3′-glucuronide, (−)-epicatechin-3′-sulfate and 3′-O-methyl-(−)-epicatechin-5-sulfate (SREMB), as flavan-3-ol and (−)-epicatechin intake. SREMB in urine proved to be a specific indicator of (−)-epicatechin intake, showing also a strong correlation with the amount of (−)-epicatechin ingested (R2: 0.86 (95% CI 0.8l; 0.92). The median recovery of (−)-epicatechin as SREMB in 24 h urine was 10% (IQR 7–13%) and we found SREMB in the majority of participants of EPIC Norfolk (83% of 24,341) with a mean concentration of 2.4 ± 3.2 µmol/L. Our results show that SREMB are suitable as biomarker of (−)-epicatechin intake. According to evaluation criteria from IARC and the Institute of Medicine, the results obtained support use of SREMB as a recovery biomarker to estimate actual intake of (−)-epicatechin

Strongly Correlated Quantum Fluids: Ultracold Quantum Gases, Quantum Chromodynamic Plasmas, and Holographic Duality

Strongly correlated quantum fluids are phases of matter that are intrinsically quantum mechanical, and that do not have a simple description in terms of weakly interacting quasi-particles. Two systems that have recently attracted a great deal of interest are the quark-gluon plasma, a plasma of strongly interacting quarks and gluons produced in relativistic heavy ion collisions, and ultracold atomic Fermi gases, very dilute clouds of atomic gases confined in optical or magnetic traps. These systems differ by more than 20 orders of magnitude in temperature, but they were shown to exhibit very similar hydrodynamic flow. In particular, both fluids exhibit a robustly low shear viscosity to entropy density ratio which is characteristic of quantum fluids described by holographic duality, a mapping from strongly correlated quantum field theories to weakly curved higher dimensional classical gravity. This review explores the connection between these fields, and it also serves as an introduction to the Focus Issue of New Journal of Physics on Strongly Correlated Quantum Fluids: from Ultracold Quantum Gases to QCD Plasmas. The presentation is made accessible to the general physics reader and includes discussions of the latest research developments in all three areas.Comment: 138 pages, 25 figures, review associated with New Journal of Physics special issue "Focus on Strongly Correlated Quantum Fluids: from Ultracold Quantum Gases to QCD Plasmas" (http://iopscience.iop.org/1367-2630/focus/Focus%20on%20Strongly%20Correlated%20Quantum%20Fluids%20-%20from%20Ultracold%20Quantum%20Gases%20to%20QCD%20Plasmas