Evolutionary psychology suggests that a woman's sexual attractiveness is based on cues of health and reproductive potential. In recent years, research has focused on the ratio of the width of the waist to the width of the hips (the waist-to-hip ratio (WHR)). A low WHR (i.e. a curvaceous body) is believed to correspond to the optimal fat distribution for high fertility, and so this shape should be highly attractive. In this paper we present evidence that weight scaled for height (the body mass index (BMI)) is the primary determinant of sexual attractiveness rather than WHR. BMI is also strongly linked to health and reproductive potential. Furthermore, we show how covariation of apparent BMI and WHR in previous studies led to the overestimation of the importance of WHR in the perception of female attractiveness. Finally, we show how visual cues, such as the perimeter^area ratio (PAR), can provide an accurate and reliable index of an individual's BMI and could be used by an observer to di¡erentiate between potential partners.

B cell development is controlled by a series of checkpoints that ensure that the immunoglobulin (Ig)-encoding genes are assembled in frame to produce a functional B cell receptor (BCR) and antibodies. The BCR consists of Ig proteins in complex with the immunoreceptor tyrosine-based activation motif (ITAM)-containing Igα and Igβ chains. Whereas the activation of Src and Syk tyrosine kinases is essential for BCR signaling, the pathways that act downstream of these kinases are incompletely defined. Previous work has revealed a key role for the p110δ isoform of phosphoinositide 3-kinase (PI3K) in agonist-induced BCR signaling; however, early B cell development and mature B cell survival, which depend on tonic BCR signaling, are not substantially affected by a deficiency in p110δ. Here, we show that in the absence of p110δ, p110α, but not p110β, can compensate to promote early B cell development in the bone marrow and B cell survival in the spleen. In the absence of both p110α and p110δ activities, pre-BCR signaling fails to suppress the production of recombination-activating gene (Rag) protein and to promote developmental progression of B cell progenitors. By contrast, p110α does not contribute to agonist-induced BCR signaling. These studies indicate that either p110α or p110δ can mediate tonic signaling from the BCR, but that only p110δ can contribute to antigen-dependent activation of B cells.

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Mouse gene-targeting studies have documented a central role of the p110␦ isoform of phosphoinositide 3-kinase (PI3K) in B-cell development and function. A defect in B-cell antigen receptor (BCR) signaling is key to this B-cell phenotype. Here we further characterize this signaling defect and report that a p110␦-selective small molecule inhibitor mirrors the effect of genetic inactivation of p110␦ in BCR signaling. p110␦ activity is indispensable for BCR-induced DNA synthesis and phosphorylation of Akt/protein kinase B (PKB), forkhead transcription factor/forkhead box O3a (FOXO3a), and p70 S6 kinase (p70 S6K), with modest effects on the phosphorylation of glycogen synthase kinase 3 ␣/␤ (GSK3␣/␤) and extracellular signal-regulated kinase (Erk). The PI3K-dependent component of intracellular calcium mobilization also completely relies on p110␦ catalytic activity. Resting B cells with inactive p110␦ fail to enter the cell cycle, correlating with an incapacity to up-regulate the expression of cyclins D2, A, and E, and to phosphorylate the retinoblastoma protein (Rb). p110␦ is also critical for interleukin 4 (IL-4)-induced phosphorylation of Akt/PKB and FOXO3a, and protection from apoptosis. Taken together, these data show that defects observed in p110␦ mutant mice are not merely a consequence of altered B-cell differentiation, and emphasize the potential utility of p110␦ as a drug target in autoimmune diseases in which B cells play a crucial role. IntroductionSignal transduction through the B-cell antigen receptor (BCR) and cytokine receptors regulates multiple biologic functions such as growth, proliferation, differentiation, and survival, depending on the maturation state of the B lymphocyte. [1][2][3][4] Intracellular signal transduction by the BCR and cytokine receptors is almost invariably dependent on the activity of the phosphoinositide 3-kinase (PI3K) signaling enzymes. 4,5 Mammals have 8 distinct isoforms of PI3K that have been divided in 3 classes on the basis of their lipid specificity and structure. 6,7 The class I subset of PI3K enzymes generate lipid second messengers that activate a plethora of downstream targets, including protein kinases (such as Akt/protein kinase B [PKB] and Bruton tyrosine kinase [Btk]), guanosine nucleotide exchange factors (such as P-Rex1 and cytohesins), GTPaseactivating proteins (such as members of the centaurin family), and adaptor molecules (such as Bam 32). [7][8][9] Class I PI3Ks are heterodimers consisting of a p110 catalytic subunit and a regulatory subunit. These PI3Ks have been further divided in the IA and IB subclasses, which signal in tyrosine kinase-driven and G protein-coupled receptor pathways, respectively.Genes for 3 class IA p110 isoforms (p110␣, p110␤, p110␦) and a single class IB PI3K isoform (p110␥) exist. p110␥ and p110␦ are mainly expressed in leukocytes, in contrast to p110␣ and p110␤, which have a broader tissue distribution. The class IA regulatory subunits have Src-homology region 2 (SH2) domains that recruit the class IA p110 catalytic subunits to p...