Facial first impressions across culture : data-driven modelling of Chinese and British perceivers’ unconstrained facial impressions

People form first impressions from facial appearance rapidly, and these impressions can have considerable social and economic consequences. Three dimensions can explain Western perceivers’ impressions of Caucasian faces: approachability, youthful-attractiveness, and dominance. Impressions along these dimensions are theorized to be based on adaptive cues to threat detection or sexual selection, making it likely that they are universal. We tested whether the same dimensions of facial impressions emerge across culture by building data-driven models of first impressions of Asian and Caucasian faces derived from Chinese and British perceivers’ unconstrained judgments. We then cross-validated the dimensions with computer-generated average images. We found strong evidence for common approachability and youthful-attractiveness dimensions across perceiver and face race, with some evidence of a third dimension akin to capability. The models explained ~75% of the variance in facial impressions. In general, the findings demonstrate substantial cross-cultural agreement in facial impressions, especially on the most salient dimensions

Development of the Human Fetal Kidney from Mid to Late Gestation in Male and Female Infants

BACKGROUND During normal human kidney development, nephrogenesis (the formation of nephrons) is complete by term birth, with the majority of nephrons formed late in gestation. The aim of this study was to morphologically examine nephrogenesis in fetal human kidneys from 20 to 41weeks of gestation. METHODS Kidney samples were obtained at autopsy from 71 infants that died acutely in utero or within 24h after birth. Using image analysis, nephrogenic zone width, the number of glomerular generations, renal corpuscle cross-sectional area and the cellular composition of glomeruli were examined. Kidneys from female and male infants were analysed separately. FINDINGS The number of glomerular generations formed within the fetal kidneys was directly proportional to gestational age, body weight and kidney weight, with variability between individuals in the ultimate number of generations (8 to 12) and in the timing of the cessation of nephrogenesis (still ongoing at 37weeks gestation in one infant). There was a slight but significant (r2=0.30, P=0.001) increase in renal corpuscle cross-sectional area from mid gestation to term in females, but this was not evident in males. The proportions of podocytes, endothelial and non-epithelial cells within mature glomeruli were stable throughout gestation. INTERPRETATION These findings highlight spatial and temporal variability in nephrogenesis in the developing human kidney, whereas the relative cellular composition of glomeruli does not appear to be influenced by gestational age.This study was supported by funding from the National Health and Medical Research Council (NHMRC) (1011136) of Australia and National Institutes of Health (NIH) USA grant 3U01DK094526-04S1 (PI A P McMahon). Author Danica Ryan was the recipient of the Biomedicine Discovery Scholarship from Monash University and author Megan R. Sutherland was supported by a NHMRC CJ Martin Fellowship

Comprehensive Biotransformation Analysis of Phenylalanine-Tyrosine Metabolism Reveals Alternative Routes of Metabolite Clearance in Nitisinone-Treated Alkaptonuria

Metabolomic analyses in alkaptonuria (AKU) have recently revealed alternative pathways in phenylalanine-tyrosine (phe-tyr) metabolism from biotransformation of homogentisic acid (HGA), the active molecule in this disease. The aim of this research was to study the phe-tyr metabolic pathway and whether the metabolites upstream of HGA, increased in nitisinone-treated patients, also undergo phase 1 and 2 biotransformation reactions. Metabolomic analyses were performed on serum and urine from patients partaking in the SONIA 2 phase 3 international randomised-controlled trial of nitisinone in AKU (EudraCT no. 2013-001633-41). Serum and urine samples were taken from the same patients at baseline (pre-nitisinone) then at 24 and 48 months on nitisinone treatment (patients N = 47 serum; 53 urine) or no treatment (patients N = 45 serum; 50 urine). Targeted feature extraction was performed to specifically mine data for the entire complement of theoretically predicted phase 1 and 2 biotransformation products derived from phenylalanine, tyrosine, 4-hydroxyphenylpyruvic acid and 4-hydroxyphenyllactic acid, in addition to phenylalanine-derived metabolites with known increases in phenylketonuria. In total, we observed 13 phase 1 and 2 biotransformation products from phenylalanine through to HGA. Each of these products were observed in urine and two were detected in serum. The derivatives of the metabolites upstream of HGA were markedly increased in urine of nitisinone-treated patients (fold change 1.2–16.2) and increases in 12 of these compounds were directly proportional to the degree of nitisinone-induced hypertyrosinaemia (correlation coefficient with serum tyrosine = 0.2–0.7). Increases in the urinary phenylalanine metabolites were also observed across consecutive visits in the treated group. Nitisinone treatment results in marked increases in a wider network of phe-tyr metabolites than shown before. This network comprises alternative biotransformation products from the major metabolites of this pathway, produced by reactions including hydration (phase 1) and bioconjugation (phase 2) of acetyl, methyl, acetylcysteine, glucuronide, glycine and sulfate groups. We propose that these alternative routes of phe-tyr metabolism, predominantly in urine, minimise tyrosinaemia as well as phenylalanaemia

Metabolomic studies in the inborn error of metabolism alkaptonuria reveal new biotransformations in tyrosine metabolism

Alkaptonuria (AKU) is an inherited disorder of tyrosine metabolism caused by lack of active enzyme homogentisate 1,2-dioxygenase (HGD). The primary consequence of HGD deficiency is increased circulating homogentisic acid (HGA), the main agent in the pathology of AKU disease. Here we report the first metabolomic analysis of AKU homozygous Hgd knockout (Hgd(−/−)) mice to model the wider metabolic effects of Hgd deletion and the implication for AKU in humans. Untargeted metabolic profiling was performed on urine from Hgd(−/−) AKU (n = 15) and Hgd(+/−) non-AKU control (n = 14) mice by liquid chromatography high-resolution time-of-flight mass spectrometry (Experiment 1). The metabolites showing alteration in Hgd(−/−) were further investigated in AKU mice (n = 18) and patients from the UK National AKU Centre (n = 25) at baseline and after treatment with the HGA-lowering agent nitisinone (Experiment 2). A metabolic flux experiment was carried out after administration of (13)C-labelled HGA to Hgd(−/−)(n = 4) and Hgd(+/−)(n = 4) mice (Experiment 3) to confirm direct association with HGA. Hgd(−/−) mice showed the expected increase in HGA, together with unexpected alterations in tyrosine, purine and TCA-cycle pathways. Metabolites with the greatest abundance increases in Hgd(−/−) were HGA and previously unreported sulfate and glucuronide HGA conjugates, these were decreased in mice and patients on nitisinone and shown to be products from HGA by the (13)C-labelled HGA tracer. Our findings reveal that increased HGA in AKU undergoes further metabolism by mainly phase II biotransformations. The data advance our understanding of overall tyrosine metabolism, demonstrating how specific metabolic conditions can elucidate hitherto undiscovered pathways in biochemistry and metabolism

The C4 Clustering Algorithm: Clusters of Galaxies in the Sloan Digital Sky Survey

We present the "C4 Cluster Catalog", a new sample of 748 clusters of galaxies identified in the spectroscopic sample of the Second Data Release (DR2) of the Sloan Digital Sky Survey (SDSS). The C4 cluster--finding algorithm identifies clusters as overdensities in a seven-dimensional position and color space, thus minimizing projection effects which plagued previous optical clusters selection. The present C4 catalog covers ~2600 square degrees of sky with groups containing 10 members to massive clusters having over 200 cluster members with redshifts. We provide cluster properties like sky location, mean redshift, galaxy membership, summed r--band optical luminosity (L_r), velocity dispersion, and measures of substructure. We use new mock galaxy catalogs to investigate the sensitivity to the various algorithm parameters, as well as to quantify purity and completeness. These mock catalogs indicate that the C4 catalog is ~90% complete and 95% pure above M_200 = 1x10^14 solar masses and within 0.03 <=z <= 0.12. The C4 algorithm finds 98% of X-ray identified clusters and 90% of Abell clusters within 0.03 <= z <= 0.12. We show that the L_r of a cluster is a more robust estimator of the halo mass (M_200) than the line-of-sight velocity dispersion or the richness of the cluster. L_r. The final SDSS data will provide ~2500 C4 clusters and will represent one of the largest and most homogeneous samples of local clusters.Comment: 32 pages of figures and text accepted in AJ. Electronic version with additional tables, links, and figures is available at http://www.ctio.noao.edu/~chrism/c

Impact of Nitisinone on the Cerebrospinal Fluid Metabolome of a Murine Model of Alkaptonuria

BackgroundNitisinone-induced hypertyrosinaemia is well documented in Alkaptonuria (AKU), and there is uncertainty over whether it may contribute to a decline in cognitive function and/or mood by altering neurotransmitter metabolism. The aim of this work was to evaluate the impact of nitisinone on the cerebrospinal fluid (CSF) metabolome in a murine model of AKU, with a view to providing additional insight into metabolic changes that occur following treatment with nitisinone.Methods17 CSF samples were collected from BALB/c Hgd-/- mice (n = 8, treated with nitisinone-4 mg/L and n = 9, no treatment). Samples were diluted 1:1 with deionised water and analysed using a 1290 Infinity II liquid chromatography system coupled to a 6550 quadrupole time-of-flight mass spectrometry (Agilent, Cheadle, UK). Raw data were processed using a targeted feature extraction algorithm and an established in-house accurate mass retention time database. Matched entities (±10 ppm theoretical accurate mass and ±0.3 min retention time window) were filtered based on their frequency and variability. Experimental groups were compared using a moderated t-test with Benjamini-Hochberg false-discovery rate adjustment.ResultsL-Tyrosine, N-acetyl-L-tyrosine, γ-glutamyl-L-tyrosine, p-hydroxyphenylacetic acid, and 3-(4-hydroxyphenyl)lactic acid were shown to increase in abundance (log2 fold change 2.6-6.9, 3/5 were significant p &lt; 0.05) in the mice that received nitisinone. Several other metabolites of interest were matched, but no significant differences were observed, including the aromatic amino acids phenylalanine and tryptophan, and monoamine metabolites adrenaline, 3-methoxy-4-hydroxyphenylglycol, and octopamine.ConclusionsEvaluation of the CSF metabolome of a murine model of AKU revealed a significant increase in the abundance of a limited number of metabolites following treatment with nitisinone. Further work is required to understand the significance of these findings and the mechanisms by which the altered metabolite abundances occur

Preparation of anti-vicinal amino alcohols: asymmetric synthesis of D-erythro-Sphinganine, (+)-spisulosine and D-ribo-phytosphingosine

Two variations of the Overman rearrangement have been developed for the highly selective synthesis of anti-vicinal amino alcohol natural products. A MOM-ether directed palladium(II)-catalyzed rearrangement of an allylic trichloroacetimidate was used as the key step for the preparation of the protein kinase C inhibitor D-erythro-sphinganine and the antitumor agent (+)-spisulosine, while the Overman rearrangement of chiral allylic trichloroacetimidates generated by asymmetric reduction of an alpha,beta-unsaturated methyl ketone allowed rapid access to both D-ribo-phytosphingosine and L-arabino-phytosphingosine

Studies in alkaptonuria reveal new roles beyond drug clearance for phase I and II biotransformations in tyrosine metabolism

AbstractBackground and Purposealkaptonuria (AKU) is an inherited disorder of tyrosine metabolism caused by lack of the enzyme homogentisate 1,2-dioxygenase (HGD). The primary biochemical consequence of HGD-deficiency is increased circulating homogentisic acid (HGA), which is central to AKU disease pathology. The aim of this study was to investigate the wider metabolic consequences of targeted Hgd disruption.Experimental Approachthe first metabolomic analysis of the Hgd−/− AKU mouse model was performed. Urinary metabolites altered in Hgd−/− were further validated by showing that the HGA-lowering drug nitisinone reversed their direction of alteration in AKUKey Resultscomparison of Hgd−/− (AKU) versus Hgd+/− (heterozygous control) urine revealed increases in HGA and a group of 8 previously unreported HGA-derived transformation products from phase I and II metabolism. HGA biotransformation products HGA-sulfate, HGA-glucuronide, HGA-hydrate and hydroxymethyl-HGA were also decreased in urine from both mice and patients with AKU on the HGA-lowering agent nitisinone. Hgd knockout also revealed a host of previously unrecognised associations between tyrosine, purine and TCA cycle metabolic pathways.Conclusion and ImplicationsAKU is rare, but our findings further what is currently understood about tyrosine metabolism more generally, and show for the first time that phase I and II detoxification is recruited to prevent accumulation of endogenously-produced metabolites in inborn errors of metabolism. The data highlight the misconception that phase I and II metabolic biotransformations are reserved solely for drug clearance; these are ancient mechanisms, which represent new potential treatment targets in inherited metabolic diseases.Abstract FigureBullet point summaryWhat is already known Increased circulating homogentisic acid is central to disease pathology in the inherited metabolic disease alkaptonuriaThe Hgd knockout mouse, created in our laboratory, accurately models human alkaptonuriaWhat this study adds Phase I and II biotransformations are recruited in alkaptonuria for detoxification of homogentisic acidThese data challenge misconceptions that phase I and II metabolism is solely for drug clearanceClinical significance Phase I and II metabolic processes represent new treatment targets in inherited metabolic diseasesThe molecular pathology of AKU extends much further than the known alteration to tyrosine metabolism</jats:sec

GAMA: towards a physical understanding of galaxy formation

The Galaxy And Mass Assembly (GAMA) project is the latest in a tradition of large galaxy redshift surveys, and is now underway on the 3.9m Anglo-Australian Telescope at Siding Spring Observatory. GAMA is designed to map extragalactic structures on scales of 1kpc - 1Mpc in complete detail to a redshift of z~0.2, and to trace the distribution of luminous galaxies out to z~0.5. The principal science aim is to test the standard hierarchical structure formation paradigm of Cold Dark Matter (CDM) on scales of galaxy groups, pairs, discs, bulges and bars. We will measure (1) the Dark Matter Halo Mass Function (as inferred from galaxy group velocity dispersions); (2) baryonic processes, such as star formation and galaxy formation efficiency (as derived from Galaxy Stellar Mass Functions); and (3) the evolution of galaxy merger rates (via galaxy close pairs and galaxy asymmetries). Additionally, GAMA will form the central part of a new galaxy database, which aims to contain 275,000 galaxies with multi-wavelength coverage from coordinated observations with the latest international ground- and space-based facilities: GALEX, VST, VISTA, WISE, HERSCHEL, GMRT and ASKAP. Together, these data will provide increased depth (over 2 magnitudes), doubled spatial resolution (0.7"), and significantly extended wavelength coverage (UV through Far-IR to radio) over the main SDSS spectroscopic survey for five regions, each of around 50 deg^2. This database will permit detailed investigations of the structural, chemical, and dynamical properties of all galaxy types, across all environments, and over a 5 billion year timeline.Comment: GAMA overview which appeared in the October 2009 issue of Astronomy & Geophysics, ref: Astron.Geophys. 50 (2009) 5.1

Standardized reporting of the costs of management interventions for biodiversity conservation

Effective conservation management interventions must combat threats and deliver conservation benefits at costs that can be achieved within limited budgets. Considerable effort has focused on measuring the potential benefits of conservation interventions but explicit quantification of implementation costs has been rare. Even when costs have been quantified, haphazard and inconsistent reporting means that published values are difficult to interpret. This reporting deficiency hinders progress towards building a collective understanding of the costs of management interventions across projects, and thus limits our ability to identify efficient solutions to conservation problems or attract adequate funding. We address this challenge by proposing a standardized approach to describing costs reported for conservation interventions. These standards call for researchers and practitioners to ensure the cost data they collect and report on provide enough contextual information that readers and future users can interpret the data appropriately. We suggest these standards be adopted by major conservation organizations, conservation science institutions, and journals, so that cost reporting is comparable between studies. This would support shared learning and enhance our ability to identify and perform cost-effective conservation.Funding was provided by CEED (GDI and workshop), an ARC Laureate Fellowship (HPP, BM, VA and JM), Arcadia (WJS), the Natural Environment Research Council (LVD, NE/K015419/1; NE/N014472/1) and the Wildlife Conservation Society (AJP)