Secretions of GH, FSH and LH during sleep of the normal child and the child with retarded growth]

In normal children the major GH release begins during NREM sleep of first cycle. At puberty secretion of gonadotropins is enhanced and secretion of LH occurs with the same periodicity as the sleep cycles. Two groups of dwarfish are seen: the first lacks both GH secretion during sleep and the increase of gonadotropins at puberty. The second group exhibits GH, LH and FSH secretion patterns similar to normal children. Study of secretion patterns of GH, FSH and LH during sleep in children can document the degree of maturation of the hypothalamic pituitary hormonal system.     

Evidence for Fisher's dominance theory: how many 'special cases'?

Dominance, its genetic basis and evolution has been at the heart of one of the most intense controversies in the history of genetics. For more than eighty years the existence of dominance modifiers, genetic elements controlling dominance-recessivity interactions, has been suggested as a theoretical possibility, but the modifier elements themselves have remained elusive. A recent study of the self-incompatibility locus in flowering plants provided the first empirical evidence for such genetic elements: small non-coding RNAs that control dominance-recessivity by mediating methylation of the promoter of the recessive allele. Theory has shown that several biological situations are favorable for the evolution of dominance modifiers. We argue that the elucidation of this mechanism of dominance opens up new research avenues that could lead to uncovering dominance modifiers in other genetic systems, such as genes controlling Batesian and Müllerian mimicry or host-parasite interactions, thereby shedding light on the generality of the proposed mechanism.     

LPA induces osteoblast differentiation through interplay of two receptors: LPA1 and LPA4

The bioactive phospholipid, lysophosphatidic acid (LPA), acting through at least five distinct receptors LPA1–LPA5, plays important roles in numerous biological processes. Here we report that LPA induces osteoblastic differentiation of human mesenchymal stem cells hMSC‐TERT. We find that hMSC‐TERT mostly express two LPA receptors, LPA1 and LPA4, and undergo osteoblastic differentiation in serum‐containing medium. Inhibition of LPA1 with Ki16425 completely abrogates osteogenesis, indicating that this process is mediated by LPA in the serum through activation of LPA1. In contrast to LPA1, down‐regulation of LPA4 expression with shRNA significantly increases osteogenesis, suggesting that this receptor normally exerts negative effects on differentiation. Mechanistically, we find that in hMSC‐TERT, LPA induces a rise in both cAMP and Ca²⁺. The rise in Ca²⁺ is completely abolished by Ki16425, whereas LPA‐mediated cAMP increase is not sensitive to Ki16425. To test if LPA signaling pathways controlling osteogenesis in vitro translate into animal physiology, we evaluated the bones of LPA4‐deficient mice. Consistent with the ability of LPA4 to inhibit osteoblastic differentiation of stem cells, LPA4‐deficient mice have increased trabecular bone volume, number, and thickness. J. Cell. Biochem. 109: 794–800, 2010. © 2010 Wiley‐Liss, Inc.     

Wnt5a induces homodimerization and activation of Ror2 receptor tyrosine kinase

Wnts are secreted glycoproteins that control vital biological processes, including embryogenesis, organogenesis and tumorigenesis. Wnts are classified into several subfamilies depending on the signaling pathways they activate, with the canonical subfamily activating the Wnt/beta-catenin pathway and the non-canonical subfamily activating a variety of other pathways, including the Wnt/calcium signaling and the small GTPase/c-Jun NH2-terminal kinase pathway. Wnts bind to a membrane receptor Frizzled and a co-receptor, the low-density lipoprotein receptor related protein. More recently, both canonical and non-canonical Wnts were shown to bind the Ror2 receptor tyrosine kinase. Ror2 is an orphan receptor that plays crucial roles in skeletal morphogenesis and promotes osteoblast differentiation and bone formation. Here we examine the effects of a canonical Wnt3a and a non-canonical Wnt5a on the signaling of the Ror2 receptor. We demonstrate that even though both Wnt5a and Wnt3a bound Ror2, only Wnt5a induced Ror2 homo-dimerization and tyrosine phosphorylation in U2OS human osteoblastic cells. Furthermore, Wnt5a treatment also resulted in increased phosphorylation of the Ror2 substrate, 14-3-3beta scaffold protein, indicating that Wnt5a binding causes activation of the Ror2 signaling cascade. Functionally, Wnt5a recapitulated the Ror2 activation phenotype, enhancing bone formation in the mouse calvarial bone explant cultures and potentiating osteoblastic differentiation of human mesenchymal stem cells. The effect of Wnt5a on osteoblastic differentiation was largely abolished upon Ror2 down-regulation. Thus we show that Wnt5a activates the classical receptor tyrosine kinase signaling cascade through the Ror2 receptor in cells of osteoblastic origin.     

Origin and diversification dynamics of self-incompatibility haplotypes

Self-incompatibility (SI) is a genetic system found in some hermaphrodite plants. Recognition of pollen by pistils expressing cognate specificities at two linked genes leads to rejection of self pollen and pollen from close relatives, i.e., to avoidance of self-fertilization and inbred matings, and thus increased outcrossing. These genes generally have many alleles, yet the conditions allowing the evolution of new alleles remain mysterious. Evolutionary changes are clearly necessary in both genes, since any mutation affecting only one of them would result in a nonfunctional self-compatible haplotype. Here, we study diversification at the S-locus (i.e., a stable increase in the total number of SI haplotypes in the population, through the incorporation of new SI haplotypes), both deterministically (by investigating analytically the fate of mutations in an infinite population) and by simulations of finite populations. We show that the conditions allowing diversification are far less stringent in finite populations with recurrent mutations of the pollen and pistil genes, suggesting that diversification is possible in a panmictic population. We find that new SI haplotypes emerge fastest in populations with few SI haplotypes, and we discuss some implications for empirical data on S-alleles. However, allele numbers in our simulations never reach values as high as observed in plants whose SI systems have been studied, and we suggest extensions of our models that may reconcile the theory and data.     

How does pollination mutualism affect the evolution of prior self‐fertilization? A model

The mode of pollination is often neglected regarding the evolution of selfing. Yet the distribution of mating systems seems to depend on the mode of pollination, and pollinators are likely to interfere with selfing evolution, since they can cause strong selective pressures on floral traits. Most selfing species reduce their investment in reproduction, and display smaller flowers, with less nectar and scents (referred to as selfing syndrome). We model the evolution of prior selfing when it affects both the demography of plants and pollinators and the investment of plants in pollination. Including the selfing syndrome in the model allows to predict several outcomes: plants can evolve either toward complete outcrossing, complete selfing, or to a stable mixed‐mating system, even when inbreeding depression is high. We predict that the evolution to high prior selfing could lead to evolutionary suicides, highlighting the importance of merging demography and evolution in models. The consequence of the selfing syndrome on plant–pollinator interactions could be a widespread mechanism driving the evolution of selfing in animal‐pollinated taxa.     

Molecular mechanisms of dominance evolution in Müllerian mimicry

Natural selection acting on dominance between adaptive alleles at polymorphic loci can be sufficiently strong for dominance to evolve. However, the molecular mechanisms underlying such evolution are generally unknown. Here, using Müllerian mimicry as a case‐study for adaptive morphological variation, we present a theoretical analysis of the invasion of dominance modifiers altering gene expression through different molecular mechanisms. Toxic species involved in Müllerian mimicry exhibit warning coloration, and converge morphologically with other toxic species of the local community, due to positive frequency‐dependent selection acting on these colorations. Polymorphism in warning coloration may be maintained by migration–selection balance with fine scale spatial heterogeneity. We modeled a dominance modifier locus altering the expression of the warning coloration locus, targeting one or several alleles, acting in cis or trans, and either enhancing or repressing expression. We confirmed that dominance could evolve when balanced polymorphism was maintained at the color locus. Dominance evolution could result from modifiers enhancing one allele specifically, irrespective of their linkage with the targeted locus. Nonspecific enhancers could also persist in populations, at frequencies tightly depending on their linkage with the targeted locus. Altogether, our results identify which mechanisms of expression alteration could lead to dominance evolution in polymorphic mimicry.