Impact of UV Radiation on the Raman Signal of Cystine: Implications for the Detection of S-rich Organics on Mars.

Traces of life may have been preserved in ancient martian rocks in the form of molecular fossils. Yet the surface of Mars is continuously exposed to intense UV radiation detrimental to the preservation of organics. Because the payload of the next rovers going to Mars to seek traces of life will comprise Raman spectroscopy tools, laboratory simulations that document the effect of UV radiation on the Raman signal of organics appear critically needed. The experiments conducted here evidence that UV radiation is directly responsible for the increase of disorder and for the creation of electronic defects and radicals within the molecular structure of S-rich organics such as cystine, enhancing the contribution of light diffusion processes to the Raman signal. The present results suggest that long exposure to UV radiation would ultimately be responsible for the total degradation of the Raman signal of cystine. Yet because the degradation induced by UV is not instantaneous, it should be possible to detect freshly excavated S-rich organics with the Raman instruments on board the rovers. Alternatively, given the very short lifetime of organic fluorescence (nanoseconds) compared to most mineral luminescence (micro- to milliseconds), exploiting fluorescence signals might allow the detection of S-rich organics on Mars. In any case, as illustrated here, we should not expect to detect pristine S-rich organic compounds on Mars, but rather by-products of their degradation.

Parental and child genetic contributions to obesity traits in early life based on 83 loci validated in adults: the FAMILY study.

BACKGROUND: The genetic influence on child obesity has not been fully elucidated. OBJECTIVE: This study investigated the parental and child contributions of 83 adult body mass index (BMI)-associated single-nucleotide polymorphisms (SNPs) to obesity-related traits in children from birth to 5 years old. METHODS: A total of 1402 individuals were genotyped for 83 SNPs. An unweighted genetic risk score (GRS) was generated by the sum of BMI-increasing alleles. Repeated weight and length/height were measured at birth, 1, 2, 3 and 5 years of age, and age-specific and sex-specific weight and BMI Z-scores were computed. RESULTS: The GRS was significantly associated with birthweight Z-score (P = 0.03). It was also associated with weight/BMI Z-score gain between birth and 5 years old (P = 0.02 and 6.77 × 10-3 , respectively). In longitudinal analyses, the GRS was associated with weight and BMI Z-score from birth to 5 years (P = 5.91 × 10-3 and 5.08 × 10-3 , respectively). The maternal effects of rs3736485 in DMXL2 on weight and BMI variation from birth to 5 years were significantly greater compared with the paternal effects by Z test (P = 1.53 × 10-6 and 3.75 × 10-5 , respectively). CONCLUSIONS: SNPs contributing to adult BMI exert their effect at birth and in early childhood. Parent-of-origin effects may occur in a limited subset of obesity predisposing SNPs.

Expressed fusion gene landscape and its impact in multiple myeloma.

Multiple myeloma is a plasma cell malignancy characterized by recurrent IgH translocations and well described genomic heterogeneity. Although transcriptome profiles in multiple myeloma has been described, landscape of expressed fusion genes and their clinical impact remains unknown. To provide a comprehensive and detailed fusion gene cartography and suggest new mechanisms of tumorigenesis in multiple myeloma, we performed RNA sequencing in a cohort of 255 newly diagnosed and homogeneously treated multiple myeloma patients with long follow-up. Here, we report that patients have on average 5.5 expressed fusion genes. Kappa and lambda light chains and IgH genes are main partners in a third of all fusion genes. We also identify recurrent fusion genes that significantly impact both progression-free and overall survival and may act as drivers of the disease. Lastly, we find a correlation between the number of fusions, the age of patients and the clinical outcome, strongly suggesting that genomic instability drives prognosis of the disease.

Burial-induced oxygen-isotope re-equilibration of fossil foraminifera explains ocean paleotemperature paradoxes.

Oxygen-isotope compositions of fossilised planktonic and benthic foraminifera tests are used as proxies for surface- and deep-ocean paleotemperatures, providing a continuous benthic record for the past 115 Ma. However, visually imperceptible processes can alter these proxies during sediment burial. Here, we investigate the diffusion-controlled re-equilibration process with experiments exposing foraminifera tests to elevated pressures and temperatures in isotopically heavy artificial seawater (H218O), followed by scanning electron microscopy and quantitative NanoSIMS imaging: oxygen-isotope compositions changed heterogeneously at submicrometer length scales without any observable modifications of the test ultrastructures. In parallel, numerical modelling of diffusion during burial shows that oxygen-isotope re-equilibration of fossil foraminifera tests can cause significant overestimations of ocean paleotemperatures on a time scale of 107 years under natural conditions. Our results suggest that the late Cretaceous and Paleogene deep-ocean and high-latitude surface-ocean temperatures were significantly lower than is generally accepted, thereby explaining the paradox of the low equator-to-pole surface-ocean thermal gradient inferred for these periods.

Empirical evaluation of the Q-Genie tool: a protocol for assessment of effectiveness.

INTRODUCTION: Meta-analyses of genetic association studies are affected by biases and quality shortcomings of the individual studies. We previously developed and validated a risk of bias tool for use in systematic reviews of genetic association studies. The present study describes a larger empirical evaluation of the Q-Genie tool. METHODS AND ANALYSIS: MEDLINE, Embase, Global Health and the Human Genome Epidemiology Network will be searched for published meta-analyses of genetic association studies. Twelve reviewers in pairs will apply the Q-Genie tool to all studies in included meta-analyses. The Q-Genie will then be evaluated on its ability to (i) increase precision after exclusion of low quality studies, (ii) decrease heterogeneity after exclusion of low quality studies and (iii) good agreement with experts on quality rating by Q-Genie. A qualitative assessment of the tool will also be conducted using structured questionnaires. DISCUSSION: This systematic review will quantitatively and qualitatively assess the Q-Genie's ability to identify poor quality genetic association studies. This information will inform the selection of studies for inclusion in meta-analyses, conduct sensitivity analyses and perform metaregression. Results of this study will strengthen our confidence in estimates of the effect of a gene on an outcome from meta-analyses, ultimately bringing us closer to deliver on the promise of personalised medicine. ETHICS AND DISSEMINATION: An updated Q-Genie tool will be made available from the Population Genomics Program website and the results will be submitted for a peer-reviewed publication.

Dietary fibre linked to decreased inflammation in overweight minority youth.

OBJECTIVE: The objective of this study was to examine the relationship between diet and inflammation, and adiposity in minority youth. DESIGN AND METHODS: The study was designed as a cross-sectional analysis of 142 overweight (≥85th body mass index percentile) Hispanic and African-American adolescents (14-18 years) with the following measures: anthropometrics, adiposity via magnetic resonance imaging, dietary intake via 24-h dietary recalls, and inflammation markers from fasting blood draws utilizing a multiplex panel. Partial correlations were estimated and analysis of covariance (ancova) models fit to examine the relationship among dietary variables, inflammation markers and adiposity measures with the following a priori covariates: Tanner stage, ethnicity, sex, total energy intake, total body fat and total lean mass. RESULTS: Inference based on ancova models showed that the highest tertile of fibre intake (mean intake of 21.3 ± 6.1 g d(-1) ) vs. the lowest tertile of fibre intake (mean intake of 7.4 ± 1.8 g d(-1) ) was associated with 36% lower plasminogen activator inhibitor-1 (P = 0.02) and 43% lower resistin (P = 0.02), independent of covariates. Similar results were seen for insoluble fibre. No other dietary variables included in this study were associated with inflammation markers. CONCLUSIONS: These results suggest that increases in dietary fibre could play an important role in lowering inflammation and therefore metabolic disease risk in high-risk minority youth.

Origin and age of the earliest Martian crust from meteorite NWA 7533.

The ancient cratered terrain of the southern highlands of Mars is thought to hold clues to the planet's early differentiation, but until now no meteoritic regolith breccias have been recovered from Mars. Here we show that the meteorite Northwest Africa (NWA) 7533 (paired with meteorite NWA 7034) is a polymict breccia consisting of a fine-grained interclast matrix containing clasts of igneous-textured rocks and fine-grained clast-laden impact melt rocks. High abundances of meteoritic siderophiles (for example nickel and iridium) found throughout the rock reach a level in the fine-grained portions equivalent to 5 per cent CI chondritic input, which is comparable to the highest levels found in lunar breccias. Furthermore, analyses of three leucocratic monzonite clasts show a correlation between nickel, iridium and magnesium consistent with differentiation from impact melts. Compositionally, all the fine-grained material is alkalic basalt, chemically identical (except for sulphur, chlorine and zinc) to soils from Gusev crater. Thus, we propose that NWA 7533 is a Martian regolith breccia. It contains zircons for which we measured an age of 4,428 ± 25 million years, which were later disturbed 1,712 ± 85 million years ago. This evidence for early crustal differentiation implies that the Martian crust, and its volatile inventory, formed in about the first 100 million years of Martian history, coeval with earliest crust formation on the Moon and the Earth. In addition, incompatible element abundances in clast-laden impact melt rocks and interclast matrix provide a geochemical estimate of the average thickness of the Martian crust (50 kilometres) comparable to that estimated geophysically.

Contribution of 24 obesity-associated genetic variants to insulin resistance, pancreatic beta-cell function and type 2 diabetes risk in the French population.

CONTEXT: Obesity is the major determinant of type 2 diabetes (T2D), presumably through its effect on insulin resistance. Genome-wide association studies reported many single-nucleotide polymorphisms (SNPs) that increase obesity risk and body mass index (BMI), but their impact on T2D-related traits and risk is unclear. OBJECTIVE: We aimed at analyzing the effect of 24 obesity risk alleles, separately and in combination, on variation of both insulin resistance and ß-cell dysfunction, and on T2D risk. DESIGN: We genotyped 24 obesity-associated SNPs and calculated an obesity genotype score (sum of the obesity risk alleles per individual). We analyzed the contribution of each SNP and this score to the variation of four metabolic indices: homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of the pancreatic ß-cell function (HOMA-B), insulin sensitivity index (ISI) and insulinogenic index (II) (in up to 8050 nondiabetic French individuals) and to T2D risk (in 2077 T2D cases and 3085 controls). RESULTS: We found a highly significant effect of the obesity genotype score on increased insulin resistance adjusted for age and gender (ß=0.02; P-value=7.16 × 10(-9) for HOMA-IR). Individually, we identified nominal or significant association between increased insulin resistance and risk alleles in FAIM2, FTO, GNPDA2, MC4R, NPC1, PTER and SH2B1. Most signals, including the obesity genotype score and FTO SNP, were also associated with increased ß-cell function (ß=0.01; P-value=1.05 × 10(-6) and ß=0.04; P-value=3.45 × 10(-4), respectively). In our T2D case-control study, only the obesity genotype score and the well-known FTO locus significantly contributed to T2D risk (OR=1.03; P-value=9.99 × 10(-3) and OR=1.15; P-value=9.46 × 10(-4), respectively). Adjustment for BMI abolished all significant associations. CONCLUSIONS: Genetic predisposition to obesity contributes to increased insulin resistance and to its compensation through increased ß-cell function, and weakly increases the T2D risk. These associations are mediated by BMI.

Numerical analysis of tips in viscous flow.

When a drop (or gas bubble) is placed in a strong viscous flow (e.g., a shear flow), it develops very sharp tips at its ends. Sharp tips are also formed when a viscous fluid is withdrawn from the neighborhood of its interface with the ambient air or with another fluid (selective withdrawal). However, it is observed frequently that there exists a critical flow strength above which the drop transitions toward a "jetting state" in which a jet comes out from the tip. In this paper, we look numerically for stationary drop shapes, both globally and close to the tip, which we study with very high resolution. To this end we use a boundary integral method to solve the axisymmetric flow equations for arbitrary viscosity ratios in the inertialess (Stokes) limit. Stationary states are solved for using Newton's method. This permits us to find both stable and unstable steady states and to investigate the nature of the jetting transition. The critical parameters for this transition are in reasonable agreement with slender-body theory. Excellent agreement is found with our earlier experiments in the selective withdrawal geometry [S. Courrech du Pont and J. Eggers, Phys. Rev. Lett. 96, 034501 (2006)], for which the viscosity of the phase inside the tip is negligible. We describe a scale invariance of the experimental interface profiles away from the tip. Then we investigate the highly curved tip region not considered previously with comparable precision. We find that the shape near the tip is universal, i.e., independent of the outer flow and of the geometry of the system (drop or selective withdrawal). While the tip curvature becomes extremely large, it always remains finite if surface tension is present.

Sink flow deforms the interface between a viscous liquid and air into a tip singularity.

In our experiment, an interface between a viscous liquid and air is deformed by a sink flow of constant flow rate to form a sharp tip. Using a microscope, the interface shape is recorded down to a tip size of 1 microm. The curvature at the tip is controlled by the distance h between the tip and the sink. As a critical distance h*is approached, the curvature diverges like 1/(h-h*)3and the tip becomes cone shaped. As the distance to the sink is decreased further, the opening angle of the cone vanishes like h2. No evidence for air entrainment was found, except when the tip was inside the orifice.

Knotting probability of a shaken ball-chain.

We study the formation of knots on a macroscopic ball chain, which is shaken on a horizontal plate at 12 times the acceleration of gravity. We find that above a certain critical length, the knotting probability is independent of chain length, while the time to shake out a knot increases rapidly with chain length. The probability of finding a knot after a certain time is the result of the balance of these two processes. In particular, the knotting probability tends to a constant for long chains.

Disseminated toxoplasmosis in a Mediterranean pregnant Risso's dolphin (Grampus griseus) with transplacental fetal infection.

Fatal disseminated toxoplasmosis was diagnosed in a Risso's dolphin (Grampus griseus) dam and its fetus on the basis of pathologic findings, immunohistochemistry, and structure of the parasite. The dolphin was stranded alive on the Spanish Mediterranean coast and died a few hours later. At necropsy the dam was in good condition. From the standpoint of pathology, however, it had generalized lymphadenomegaly and splenomegaly, enlargement of and multifocal hemorrhage in the adrenal glands, diffuse mucosal hemorrhage of the glandular and pyloric stomach, ulcerative glossitis and stomatitis, focal erosions and reddening of the laryngeal appendix, and severe paraotic sinusitis with intralesional nematodes Crassicauda grampicola. The dolphin was pregnant, most probably in the first gestational trimester. The most prominent microscopic lesions were multifocal granulomatous encephalomyelitis, diffuse subacute interstitial pneumonia, mild multifocal necrotizing hepatitis and nonsuppurative cholangiohepatitis, gastritis and adrenalitis, mild lymphoid depletion, medullary sinus and follicular histyocitosis, and systemic hemosiderosis. The fetus had foci of coagulative and lytic necrosis in the kidneys, the lung, and the heart. Most lesions were associated with tachyzoites and tissue cysts of Toxoplasma gondii. The diagnosis was confirmed immunohistochemically. This is the first report on toxoplasmosis in a Risso's dolphin (G. griseus) and on transplacental transmission to an early-stage fetus in any cetaceans.

Similar mechanisms underlie curvature comparison by static and dynamic touch.

In four experiments, we tested whether haptic comparison of curvature ranging from -4/m to +4/m is qualitatively the same for static and for dynamic touch. In Experiments 1 and 3, we tested whether static and dynamic curvature discrimination are based on height differences, attitude (slope) differences, curvature differences, or a combination of these geometrical variables. It was found that both static and dynamic hepatic curvature discrimination are based on attitude differences. In Experiments 2 and 4, we tested whether this mechanism leads to errors in the comparison of stimuli with different lengths for static and dynamic touch, respectively. If the judgments are based on attitude differences, subjects will make systematic errors in these comparisons. In both experiments, we found that subjects compared the curvatures of strips of the same length vertically, whereas they made systematic errors if they were required to compare the curvatures of strips of different lengths. Longer stimuli were judged to be more curved than shorter stimuli with the same curvature. We conclude that similar mechanisms underlie static and dynamic haptic curvature comparison. Moreover, additional data comparison showed that static and dynamic curvature comparison is not only qualitatively, but also quantitatively similar.

Effect of prokinetics in children with recurrent nocturnal retrosternal pain.

BACKGROUND: Children rarely present with vague complaints of nocturnal recurrent retrosternal or upper-abdominal, epigastric, pain. Dysmotility of the upper gastrointestinal tract, including gastro-oesophageal reflux, might be at the origin of these manifestations. OBJECTIVE: To evaluate the clinical effect of prokinetics (cisapride) in children with recurrent nocturnal retrosternal pain, and to measure the effect of cisapride with a combined oesophageal ambulatory 24 h pH and pressure monitoring. PATIENTS: Twelve children, mean age 9.5 years (range 4.1-14.0 years), with nocturnal recurrent retrosternal pain for more than 6 months, occurring at least three times a week. METHODS: Single-blinded prospective study, with two periods of 2-3 weeks during which cisapride was administered, alternated with two placebo periods of the same duration. Clinical evaluation, and assessment with oesophageal pH and pressure monitoring. RESULTS: Cisapride was related to a temporary relief of the symptoms in 10/12 children. The improvement was demonstrated through a normalization of pH monitoring, and an increase in amplitude and duration of the contractions in the lower oesophagus. CONCLUSION: Cisapride improves complaints of recurrent nocturnal retrosternal pain in children.

Anisotropy in haptic curvature and shape perception.

An investigation was undertaken into whether haptic comparison of curvature and of shape is influenced by the length/width ratio of the hand. For this purpose three experiments were conducted to test the curvature matching of curved strips (experiment 1), the curvature matching of cylindrically curved hand-sized surfaces (experiment 2), and the shape discrimination of elliptically curved hand-sized surfaces (experiment 3). The orientation of the stimuli with respect to the fingers was varied. The results of the two matching experiments showed that a given curvature is judged to be more curved when touched along the fingers than when touched across the fingers. The phenomenal flatness along and across the fingers was found to be different and subject dependent. The results of the shape-discrimination experiment showed that the orientation of ellipsoidal surfaces influences the judgments of the shapes of these surfaces. This influence could be predicted on the basis of results of the second matching experiment. It is concluded that similar mechanisms underlie the (anisotropic) perception of curvature and shape. For the major part the trends in the results can be explained by the length/width ratio of the hand and the phenomenal flatnesses.

The influence of stimulus tilt on haptic curvature matching and discrimination by dynamic touch.

We investigated whether haptic comparison of the curvature of strips is influenced by the tilt (the average slope relative to the horizontal) of the curved strips. This particular stimulus manipulation was chosen to decide between two broad ways in which dynamic curvature comparison might be done: on the basis of the attitude (slope) differences over the surfaces or on the basis of the attitude (slope) differences between successively presented surfaces. For this purpose we conducted matching and discrimination experiments in which strips of constant curvature 9 cm long were touched dynamically and the tilts of the strips were varied. The results of the matching experiment showed some influence of tilt: the strips were judged to be slightly more curved if the tilt was nonzero than if it was zero. The results of the discrimination experiment did not show an effect of tilt. Because the attitude (slope) differences over the surfaces were independent of the tilt it is concluded that curvature comparison is based primarily on attitude differences over the curved surfaces.

Haptic curvature discrimination at several regions of the hand.

Static haptic discrimination of the curvature of convex, concave, or straight 20-cm-long strips was investigated for nine placements on the hand. In one condition, the strips were touched with the palmar side of the hand, and in the other condition, with the dorsal side. The influence of the lengths of the strips, and thus of contact lengths, was also investigated. For all placements, discrimination was poorer in the dorsal than in the palmar condition, owing to poorer cutaneous resolution on the dorsal side of the hand (the kinesthetic stimulation was the same in both conditions). Thus cutaneous stimulation is important. In both experiments, performance appeared to depend primarily on contact length. Moreover, the discrimination thresholds for all different placements and contact lengths followed the same trend. We conclude that in these experiments the effective stimulus for the discrimination of curved strips is the total difference of local surface attitude--that is, the slope difference over the far ends of the stimulus.