Although many accounts of facial attractiveness propose that femininity in women's faces indicates high levels of oestrogen, there is little empirical evidence in support of this assumption. Here, we used assays for urinary metabolites of oestrogen (oestrone-3-glucuronide, E1G) and progesterone (pregnanediol-3-glucuronide, P3G) to investigate the relationship between circulating gonadal hormones and ratings of the femininity, attractiveness and apparent health of women's faces. Positive correlations were observed between late follicular oestrogen and ratings of femininity, attractiveness and health. Positive correlations of luteal progesterone and health and attractiveness ratings were marginally significant. Ratings of facial attributions did not relate to hormone levels for women wearing make-up when photographed. There was no effect of sex of rater on the relationships between oestrogen and ratings of facial appearance. These findings demonstrate that female facial appearance holds detectable cues to reproductive health that are considered attractive by other people.

Numerous researchers have examined the effects of skin condition, including texture and color, on the perception of health, age, and attractiveness in human faces. They have focused on facial color distribution, homogeneity of pigmentation, or skin quality. We here investigate the role of overall skin color in determining perceptions of health from faces by allowing participants to manipulate the skin portions of color-calibrated Caucasian face photographs along CIELab color axes. To enhance healthy appearance, participants increased skin redness (a*), providing additional support for previous findings that skin blood color enhances the healthy appearance of faces. Participants also increased skin yellowness (b*) and lightness (L*), suggesting a role for high carotenoid and low melanin coloration in the healthy appearance of faces. The color preferences described here resemble the red and yellow color cues to health displayed by many species of nonhuman animals.

No abstract

Skin blood perfusion and oxygenation depends upon cardiovascular, hormonal and circulatory health in humans and provides socio-sexual signals of underlying physiology, dominance and reproductive status in some primates. We allowed participants to manipulate colour calibrated facial photographs along empirically-measured oxygenated and deoxygenated blood colour axes both separately and simultaneously, to optimise healthy appearance. Participants increased skin blood colour, particularly oxygenated, above basal levels to optimise healthy appearance. We show, therefore, that skin blood perfusion and oxygenation influence perceived health in a way that may be important to mate choice.

We demonstrate convincing evidence that SUFU mutations can cause classical Gorlin syndrome. Our study redefines the risk of medulloblastoma in Gorlin syndrome, dependent on the underlying causative gene. Previous reports have found a 5% risk of medulloblastoma in Gorlin syndrome. We found a < 2% risk in PTCH1 mutation-positive individuals, with a risk up to 20× higher in SUFU mutation-positive individuals. Our data suggest childhood brain magnetic resonance imaging surveillance is justified in SUFU-related, but not PTCH1-related, Gorlin syndrome.

Perrault syndrome is a genetically and clinically heterogeneous autosomal-recessive condition characterized by sensorineural hearing loss and ovarian failure. By a combination of linkage analysis, homozygosity mapping, and exome sequencing in three families, we identified mutations in CLPP as the likely cause of this phenotype. In each family, affected individuals were homozygous for a different pathogenic CLPP allele: c.433A>C (p.Thr145Pro), c.440G>C (p.Cys147Ser), or an experimentally demonstrated splice-donor-site mutation, c.270+4A>G. CLPP, a component of a mitochondrial ATP-dependent proteolytic complex, is a highly conserved endopeptidase encoded by CLPP and forms an element of the evolutionarily ancient mitochondrial unfolded-protein response (UPR(mt)) stress signaling pathway. Crystal-structure modeling suggests that both substitutions would alter the structure of the CLPP barrel chamber that captures unfolded proteins and exposes them to proteolysis. Together with the previous identification of mutations in HARS2, encoding mitochondrial histidyl-tRNA synthetase, mutations in CLPP expose dysfunction of mitochondrial protein homeostasis as a cause of Perrault syndrome.

No abstract

Many integrin adhesion receptors bind ligands containing the Arg-Gly-Asp (RGD) peptide motif. Most integrins exhibit considerable specificity for particular ligands and can distinguish among the many conformations of RGD. In this study we identify the domain of the integrin ␤ subunit involved in determining ligand binding specificity. Chimeras of ␤3 and ␤5, the most homologous integrin ␤ subunits, were expressed with ␣v on the surface of human 293 cells. The ligand binding phenotype of each chimera was assessed using the ligands Fab-9 and fibrinogen, both of which have a binding preference for ␣v␤3. The results of the study show that when exons C and D of the ␤3 subunit (residues 95-233) are substituted into ␤5, the chimera gained the ability to bind Fab-9 with an affinity close to that of wild-type ␣v␤3. This chimera was able to mediate cell adhesion to fibrinogen. Furthermore, the swap of only a 39-residue segment of this larger domain, ␤3 residues 164 -202, into the backbone of ␤5 enabled the chimeric integrin to bind soluble Fab-9. This small domain is highly divergent among the integrin ␤ subunits, suggesting that it may play a role in determining ligand selection by all integrins.Integrins are transmembrane ␣␤ heterodimers that are responsible for most of the physical contacts between cells and the extracellular matrix. Integrins are involved in a number of tissue remodeling events including embryogenesis, angiogenesis, wound repair, and bone resorption (1-5). Integrins are also causally linked to pathological conditions such as tumor progression, thrombosis, inflammation, and osteoporosis (6 -8).The integrin protein family contains 13 ␣ and 9 ␤ subunits. These subunits can cross-pair to form heterodimers with different expression patterns and distinct ligand binding profiles (9, 10). Each integrin binds to only a limited series of ligands, ensuring that cell adhesion and migration are precisely regulated. Such precision is key to tissue remodeling.Based on their ligand recognition specificity, integrins can be divided into two broad sub-families. About one-half of the integrins bind to ligands that lack any consensus binding motif.The remaining integrins bind to the RGD 1 consensus sequence. Importantly though, even the integrins that bind to RGD display a great deal of specificity for matrix ligands (11,12). Some of this specificity is determined by contacts that are ancillary to the RGD sequence (13,14), but much of the specificity is determined by the shape of the RGD motif and the residues in its immediate vicinity. Thus, to understand the structural basis of matrix selection, it is important to understand how integrins distinguish the many conformations of RGD.The goal of the present study was to identify domain(s) within the integrin ␤ subunit that confer ligand binding specificity. As a model system, we compared the ligand binding domains of the two most homologous integrins, ␣v␤3 and ␣v␤5. The ␤3 and ␤5 subunits have 56% identity at the amino acid level (15, 16). Although both ␣v␤3 and ␣v␤5 recogn...