New Genetic and Linguistic Analyses Show Ancient Human Influence on Baobab Evolution and Distribution in Australia

This study investigates the role of human agency in the gene flow and geographical distribution of the Australian baobab, Adansonia gregorii. The genus Adansonia is a charismatic tree endemic to Africa, Madagascar, and northwest Australia that has long been valued by humans for its multiple uses. The distribution of genetic variation in baobabs in Africa has been partially attributed to human-mediated dispersal over millennia, but this relationship has never been investigated for the Australian species. We combined genetic and linguistic data to analyse geographic patterns of gene flow and movement of word-forms for A. gregorii in the Aboriginal languages of northwest Australia. Comprehensive assessment of genetic diversity showed weak geographic structure and high gene flow. Of potential dispersal vectors, humans were identified as most likely to have enabled gene flow across biogeographic barriers in northwest Australia. Genetic-linguistic analysis demonstrated congruence of gene flow patterns and directional movement of Aboriginal loanwords for A. gregorii. These findings, along with previous archaeobotanical evidence from the Late Pleistocene and Holocene, suggest that ancient humans significantly influenced the geographic distribution of Adansonia in northwest Australia.

CD99 is upregulated in placenta and astrocytomas with a differential subcellular distribution according to the malignancy stage.

In the present study, we searched for genes highly expressed in placenta and that could contribute to the establishment and maintenance of a malignant phenotype in different types of tumours, and in astrocytomas in particular. We employed a strategy based on the integration of in silico data from previously generated massively parallel signature sequencing and public serial analysis of gene expression databases. Among 12 selected genes, CD99 exhibited the highest relative mRNA expression in GBM compared to non-neoplastic brain tissues. In a larger cohort of astrocytic tumours, we further demonstrated increased CD99 expression in all malignant grades, with GBMs showing the highest values. These findings were confirmed at the protein level by Western blotting and immunohistochemistry. Additionally, we demonstrated the CD99 localisation profile in astrocytic tumours. Interestingly, CD99 expression was confined to the cytoplasm or membrane in more malignant astrocytomas, in contrast to non-neoplastic brain tissue or non-infiltrative pilocytic astrocytoma, which showed no obvious staining in these structures. Comparison of three GBM cell lines revealed higher CD99 expression at the membrane and higher migratory capacity in the A172 and U87MG lines, but lower CD99 expression and no migratory ability in the T98 line. Knocking down CD99 expression by siRNA decreased significantly the migration of both cell lines. These integrated CD99 gene and protein expression results suggest that CD99 expression in astrocytomas of different malignant grades might contribute to the infiltrative ability and support the importance of CD99 as a potential target to reduce infiltrative astrocytoma capacity in migration and invasion.

Prediction of resting energy expenditure from fat-free mass and fat mass.

On the basis of literature values, the relationship between fat-free mass (FFM), fat mass (FM), and resting energy expenditure [REE (kJ/24 h)] was determined for 213 adults (86 males, 127 females). The objectives were to develop a mathematical model to predict REE based on body composition and to evaluate the contribution of FFM and FM to REE. The following regression equations were derived: 1) REE = 1265 + (93.3 x FFM) (r2 = 0.727, P < 0.001); 2) REE = 1114 + (90.4 x FFM) + (13.2 x FM) (R2 = 0.743, P < 0.001); and 3) REE = (108 x FFM) + (16.9 x FM) (R2 = 0.986, P < 0.001). FM explained only a small part of the variation remaining after FFM was accounted for. The models that include both FFM and FM are useful in examination of the changes in REE that occur with a change in both the FFM and FM. To account for more of the variability in REE, FFM will have to be divided into organ mass and skeletal muscle mass in future analyses.

A simple, robust and rapid approach to detect carbapenemases in Gram-negative isolates by MALDI-TOF mass spectrometry: validation with triple quadripole tandem mass spectrometry, microarray and PCR.

Carbapenemases should be accurately and rapidly detected, given their possible epidemiological spread and their impact on treatment options. Here, we developed a simple, easy and rapid matrix-assisted laser desorption ionization-time of flight (MALDI-TOF)-based assay to detect carbapenemases and compared this innovative test with four other diagnostic approaches on 47 clinical isolates. Tandem mass spectrometry (MS-MS) was also used to determine accurately the amount of antibiotic present in the supernatant after 1 h of incubation and both MALDI-TOF and MS-MS approaches exhibited a 100% sensitivity and a 100% specificity. By comparison, molecular genetic techniques (Check-MDR Carba PCR and Check-MDR CT103 microarray) showed a 90.5% sensitivity and a 100% specificity, as two strains of Aeromonas were not detected because their chromosomal carbapenemase is not targeted by probes used in both kits. Altogether, this innovative MALDI-TOF-based approach that uses a stable 10-μg disk of ertapenem was highly efficient in detecting carbapenemase, with a sensitivity higher than that of PCR and microarray.

Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.

Body fat distribution, particularly centralized obesity, is associated with metabolic risk above and beyond total adiposity. We performed genome-wide association of abdominal adipose depots quantified using computed tomography (CT) to uncover novel loci for body fat distribution among participants of European ancestry. Subcutaneous and visceral fat were quantified in 5,560 women and 4,997 men from 4 population-based studies. Genome-wide genotyping was performed using standard arrays and imputed to ~2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), VAT adjusted for body mass index, and VAT/SAT ratio (a metric of the propensity to store fat viscerally as compared to subcutaneously) in the overall sample and in women and men separately. A weighted z-score meta-analysis was conducted. For the VAT/SAT ratio, our most significant p-value was rs11118316 at LYPLAL1 gene (p = 3.1 × 10E-09), previously identified in association with waist-hip ratio. For SAT, the most significant SNP was in the FTO gene (p = 5.9 × 10E-08). Given the known gender differences in body fat distribution, we performed sex-specific analyses. Our most significant finding was for VAT in women, rs1659258 near THNSL2 (p = 1.6 × 10-08), but not men (p = 0.75). Validation of this SNP in the GIANT consortium data demonstrated a similar sex-specific pattern, with observed significance in women (p = 0.006) but not men (p = 0.24) for BMI and waist circumference (p = 0.04 [women], p = 0.49 [men]). Finally, we interrogated our data for the 14 recently published loci for body fat distribution (measured by waist-hip ratio adjusted for BMI); associations were observed at 7 of these loci. In contrast, we observed associations at only 7/32 loci previously identified in association with BMI; the majority of overlap was observed with SAT. Genome-wide association for visceral and subcutaneous fat revealed a SNP for VAT in women. More refined phenotypes for body composition and fat distribution can detect new loci not previously uncovered in large-scale GWAS of anthropometric traits.

Determination of picogram levels of midazolam, and 1- and 4-hydroxymidazolam in human plasma by gas chromatography-negative chemical ionization-mass spectrometry.

Midazolam is a widely accepted probe for phenotyping cytochrome P4503A. A gas chromatography-mass spectrometry (GC-MS)-negative chemical ionization method is presented which allows measuring very low levels of midazolam (MID), 1-OH midazolam (1OHMID) and 4-OH midazolam (4OHMID), in plasma, after derivatization with the reagent N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide. The standard curves were linear over a working range of 20 pg/ml to 5 ng/ml for the three compounds, with the mean coefficients of correlation of the calibration curves (n = 6) being 0.999 for MID and 1OHMID, and 1.0 for 4OHMID. The mean recoveries measured at 100 pg/ml, 500 pg/ml, and 2 ng/ml, ranged from 76 to 87% for MID, from 76 to 99% for 1OHMID, from 68 to 84% for 4OHMID, and from 82 to 109% for N-ethyloxazepam (internal standard). Intra- (n = 7) and inter-day (n = 8) coefficients of variation determined at three concentrations ranged from 1 to 8% for MID, from 2 to 13% for 1OHMID and from 1 to 14% for 4OHMID. The percent theoretical concentrations (accuracy) were within +/-8% for MID and 1OHMID, within +/-9% for 4OHMID at 500 pg/ml and 2 ng/ml, and within +/-28% for 4OHMID at 100 pg/ml. The limits of quantitation were found to be 10 pg/ml for the three compounds. This method can be used for phenotyping cytochrome P4503A in humans following the administration of a very low oral dose of midazolam (75 microg), without central nervous system side-effects.

FTO genotype is associated with phenotypic variability of body mass index.

There is evidence across several species for genetic control of phenotypic variation of complex traits, such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using ∼170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype), is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of ∼0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI, possibly mediated by DNA methylation. Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.

Deccan volcanism linked to the Cretaceous-Tertiary boundary mass extinction: New evidence from ONGC wells in the Krishna-Godavari basin

A scientific challenge is to assess the role of Deccan volcanism in the Cretaceous-Tertiary boundary (KTB) mass extinction. Here we report on the stratigraphy and biologic effects of Deccan volcanism in eleven deep wells from the Krishna-Godavari (K-G) Basin, Andhra Pradesh, India. In these wells, two phases of Deccan volcanism record the world's largest and longest lava mega-flows interbedded in marine sediments in the K-G Basin about 1500 km from the main Deccan volcanic province. The main phase-2 eruptions (similar to 80% of total Deccan Traps) began in C29r and ended at or near the KTB, an interval that spans planktic foraminiferal zones CF1-CF2 and most of the nannofossil Micula prinsii zone, and is correlative with the rapid global warming and subsequent cooling near the end of the Maastrichtian. The mass extinction began in phase-2 preceding the first of four mega-flows. Planktic foraminifera suffered a 50% drop in species richness. Survivors suffered another 50% drop after the first mega-flow, leaving just 7 to 8 survivor species. No recovery occurred between the next three mega-flows and the mass extinction was complete with the last phase-2 mega-flow at the KTB. The mass extinction was likely the consequence of rapid and massive volcanic CO(2) and SO(2) gas emissions, leading to high continental weathering rates, global warming, cooling, acid rains, ocean acidification and a carbon crisis in the marine environment. Deccan volcanism phase-3 began in the early Danian near the C29R/C29n boundary correlative with the planktic foraminiferal zone P1a/P1b boundary and accounts for similar to 14% of the total volume of Deccan eruptions, including four of Earth's longest and largest mega-flows. No major faunal changes are observed in the intertrappeans of zone P1b, which suggests that environmental conditions remained tolerable, volcanic eruptions were less intense and/or separated by longer time intervals thus preventing runaway effects. Alternatively, early Danian assemblages evolved in adaptation to high-stress conditions in the aftermath of the mass extinction and therefore survived phase-3 volcanism. Full marine biotic recovery did not occur until after Deccan phase-3. These data suggest that the catastrophic effects of phase-2 Deccan volcanism upon the Cretaceous planktic foraminifera were a function of both the rapid and massive volcanic eruptions and the highly specialized faunal assemblages prone to extinction in a changing environment. Data from the K-G Basin indicates that Deccan phase-2 alone could have caused the KTB mass extinction and that impacts may have had secondary effects.

Common variants near MC4R are associated with fat mass, weight and risk of obesity.

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.

Body fat distribution in white and black women: different patterns of intraabdominal and subcutaneous abdominal adipose tissue utilization with weight loss.

BACKGROUND: Intraabdominal adipose tissue (IAAT) is the body fat depot most strongly related to disease risk. Weight reduction is advocated for overweight people to reduce total body fat and IAAT, although little is known about the effect of weight loss on abdominal fat distribution in different races. OBJECTIVE: We compared the effects of diet-induced weight loss on changes in abdominal fat distribution in white and black women. DESIGN: We studied 23 white and 23 black women, similar in age and body composition, in the overweight state [mean body mass index (BMI; in kg/m(2)): 28.8] and the normal-weight state (mean BMI: 24.0) and 38 never-overweight control women (mean BMI: 23.4). We measured total body fat by using a 4-compartment model, trunk fat by using dual-energy X-ray absorptiometry, and cross-sectional areas of IAAT (at the fourth and fifth lumbar vertebrae) and subcutaneous abdominal adipose tissue (SAAT) by using computed tomography. RESULTS: Weight loss was similar in white and black women (13.1 and 12.6 kg, respectively), as were losses of total fat, trunk fat, and waist circumference. However, white women lost more IAAT (P < 0.001) and less SAAT (P < 0.03) than did black women. Fat patterns regressed toward those of their respective control groups. Changes in waist circumference correlated with changes in IAAT in white women (r = 0.54, P < 0.05) but not in black women (r = 0.19, NS). CONCLUSIONS: Despite comparable decreases in total and trunk fat, white women lost more IAAT and less SAAT than did black women. Waist circumference was not a suitable surrogate marker for tracking changes in the visceral fat compartment in black women.

Distribution of arm velocity and frequency of arm usage during daily activity: objective outcome evaluation after shoulder surgery.

In clinical settings, functional evaluation of shoulder movement is primarily based on what the patient thinks he/she is able to do rather than what he/she is actually performing. We proposed a new approach for shoulder assessment based on inertial sensors to monitor arm movement in the daily routine. The detection of movement of the humerus relative to the trunk was first validated in a laboratory setting (sensitivity>95%, specificity>97%). Then, 41 control subjects and 21 patients suffering from a rotator cuff tear were evaluated (before and after surgery) using clinical questionnaires and a one-day measurement of arm movement. The quantity of movement was estimated with the movement frequency and its symmetry index (SIFr). The quality of movement was assessed using the Kolmogorov-Smirnov distance (KS) between the cumulative distribution of the arm velocity for controls and the same distribution for each patient. SIFr presented differences between patients and controls at 3 month follow-up (p<0.05) while KS showed differences also after 6 months (p<0.01). SIFr illustrated a change in dominance due to the disorder whereas KS, which appeared independent of the dominance and occupation, showed a change in movement velocity. Both parameters were correlated to clinical scores (R(2) reaching 0.5). This approach provides clinicians with new objective parameters for evaluating the functional ability of the shoulder in daily conditions, which could be useful for outcome assessment after surgery.

The data treatment dependent variability of U-Pb zircon ages obtained using mono-collector, sector field, laser ablation ICP-MS

U-Pb dating of zircons by laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) is a widely used analytical technique in Earth Sciences. For U-Pb ages below 1 billion years (1 Ga), Pb-206/U-238 dates are usually used, showing the least bias by external parameters such as the presence of initial lead and its isotopic composition in the analysed mineral. Precision and accuracy of the Pb/U ratio are thus of highest importance in LA-ICPMS geochronology. We consider the evaluation of the statistical distribution of the sweep intensities based on goodness-of-fit tests in order to find a model probability distribution fitting the data to apply an appropriate formulation for the standard deviation. We then discuss three main methods to calculate the Pb/U intensity ratio and its uncertainty in the LA-ICPMS: (1) ratio-of-the-mean intensities method, (2) mean-of-the-intensity-ratios method and (3) intercept method. These methods apply different functions to the same raw intensity vs. time data to calculate the mean Pb/U intensity ratio. Thus, the calculated intensity ratio and its uncertainty depend on the method applied. We demonstrate that the accuracy and, conditionally, the precision of the ratio-of-the-mean intensities method are invariant to the intensity fluctuations and averaging related to the dwell time selection and off-line data transformation (averaging of several sweeps); we present a statistical approach how to calculate the uncertainty of this method for transient signals. We also show that the accuracy of methods (2) and (3) is influenced by the intensity fluctuations and averaging, and the extent of this influence can amount to tens of percentage points; we show that the uncertainty of these methods also depends on how the signal is averaged. Each of the above methods imposes requirements to the instrumentation. The ratio-of-the-mean intensities method is sufficiently accurate provided the laser induced fractionation between the beginning and the end of the signal is kept low and linear. We show, based on a comprehensive series of analyses with different ablation pit sizes, energy densities and repetition rates for a 193 nm ns-ablation system that such a fractionation behaviour requires using a low ablation speed (low energy density and low repetition rate). Overall, we conclude that the ratio-of-the-mean intensities method combined with low sampling rates is the most mathematically accurate among the existing data treatment methods for U-Pb zircon dating by sensitive sector field ICPMS.

Ambulatory assessment of 3D ground reaction force using plantar pressure distribution.

This study aimed to use the plantar pressure insole for estimating the three-dimensional ground reaction force (GRF) as well as the frictional torque (T(F)) during walking. Eleven subjects, six healthy and five patients with ankle disease participated in the study while wearing pressure insoles during several walking trials on a force-plate. The plantar pressure distribution was analyzed and 10 principal components of 24 regional pressure values with the stance time percentage (STP) were considered for GRF and T(F) estimation. Both linear and non-linear approximators were used for estimating the GRF and T(F) based on two learning strategies using intra-subject and inter-subjects data. The RMS error and the correlation coefficient between the approximators and the actual patterns obtained from force-plate were calculated. Our results showed better performance for non-linear approximation especially when the STP was considered as input. The least errors were observed for vertical force (4%) and anterior-posterior force (7.3%), while the medial-lateral force (11.3%) and frictional torque (14.7%) had higher errors. The result obtained for the patients showed higher error; nevertheless, when the data of the same patient were used for learning, the results were improved and in general slight differences with healthy subjects were observed. In conclusion, this study showed that ambulatory pressure insole with data normalization, an optimal choice of inputs and a well-trained nonlinear mapping function can estimate efficiently the three-dimensional ground reaction force and frictional torque in consecutive gait cycle without requiring a force-plate.