Imprinted genes in mammals are expressed from only one of the parental chromosomes, and are crucial for placental development and fetal growth. The insulin-like growth factor II gene (Igf2) is paternally expressed in the fetus and placenta. Here we show that deletion from the Igf2 gene of a transcript (P0) specifically expressed in the labyrinthine trophoblast of the placenta leads to reduced growth of the placenta, followed several days later by fetal growth restriction. The fetal to placental weight ratio is thus increased in the absence of the P0 transcript. We show that passive permeability for nutrients of the mutant placenta is decreased, but that secondary active placental amino acid transport is initially upregulated, compensating for the decrease in passive permeability. Later the compensation fails and fetal growth restriction ensues. Our study provides experimental evidence for imprinted gene action in the placenta that directly controls the supply of maternal nutrients to the fetus, and supports the genetic conflict theory of imprinting. We propose that the Igf2 gene, and perhaps other imprinted genes, control both the placental supply of, and the genetic demand for, maternal nutrients to the mammalian fetus.

Paramedics are exposed to events involving human pain and suffering on a daily basis, many of which are the result of violence perpetrated by 1 individual on another. For the most part, these emergency workers have learned to deal with such events and take them in stride. At times, however, certain circumstances lead workers to develop an emotional connection with the victim or his or her family. When this occurs, paramedics report increased symptoms of traumatic stress. Aspects that can trigger this connection include the victim's alienation from others, profound loss, or the abuse of an innocent child. One of the coping strategies described in these circumstances is to manage the events on a cognitive and technical level while maintaining an emotional distance. Although such a strategy may be protective, it may also have long-term negative effects in terms of interpersonal relationships. This mixed-methods study attempts to better understand factors that lead to higher levels of distress among paramedics within the theoretical framework of emotional and cognitive empathy.

Restricted fetal growth is associated with postnatal mortality and morbidity and may be directly related to alterations in the capacity of the placenta to supply nutrients. We proposed previously that imprinted genes can regulate nutrient supply by the placenta. Here, we tested the hypothesis that the insulin-like growth factor 2 gene (Igf2) transcribed from the placental-specific promoter (P0) regulates the development of the diffusional permeability properties of the mouse placenta. Using mice in which placental-specific Igf2 had been deleted (P0), we measured the transfer in vivo of three inert hydrophilic solutes of increasing size ( 14 C-mannitol, 51 CrEDTA, and 14 C-inulin). At embryonic day 19, placental and fetal weights in P0 conceptuses were reduced to 66% and 76%, respectively, of wild type. In P0 mutants, the permeability⅐surface area product for the tracers at this stage of development was 68% of that of controls; this effect was independent of tracer size. Stereological analysis of histological sections revealed the surface area of the exchange barrier in the labyrinth of the mouse placenta to be reduced and thickness increased in P0 fetuses compared to wild type. As a result, the average theoretical diffusing capacity in P0 knockout placentas was dramatically reduced to 40% of that of wild-type placentas. These data show that placental Igf2 regulates the development of the diffusional exchange characteristics of the mouse placenta. This provides a mechanism for the role of imprinted genes in controlling placental nutrient supply and fetal growth. Altered placental Igf2 could be a cause of idiopathic intrauterine growth restriction in the human.

SUMMARYSecreted factors from the epicardium are believed to be important in directing heart ventricular cardiomyocyte proliferation and morphogenesis, although the specific factors involved have not been identified or characterized adequately. We found that IGF2 is the most prominent mitogen made by primary mouse embryonic epicardial cells and by a newly derived immortalized mouse embryonic epicardial cell line called MEC1. In vivo, Igf2 is expressed in the embryonic mouse epicardium during midgestation heart development. Using a whole embryo culture assay in the presence of inhibitors, we confirmed that IGF signaling is required to activate the ERK proliferation pathway in the developing heart, and that the epicardium is required for this response. Global disruption of the Igf2 gene, or conditional disruption of the two IGF receptor genes Igf1r and Insr together in the myocardium, each resulted in a significant decrease in ventricular wall proliferation and in ventricular wall hypoplasia. Ventricular cardiomyocyte proliferation in mutant embryos was restored to normal at E14.5, concurrent with the establishment of coronary circulation. Our results define IGF2 as a previously unexplored epicardial mitogen that is required for normal ventricular chamber development.

Sexual eukaryotes undergo an alternation between haploid and diploid nuclear phases. In some organisms, both the haploid and diploid phases undergo somatic development and exist as independent entities. Despite recent attention, the mechanisms by which such biphasic life cycles evolve and persist remain obscure. One explanation that has received little theoretical attention is that haploid-diploid organisms may exploit their environments more efficiently through niche differentiation of the two ploidy phases. Even in isomorphic species, in which adults are morphologically similar, slight differences in the adult phase or among juveniles may play an important ecological role and help maintain haploid-diploidy. We develop a genetic model for the evolution of life cycles that incorporates density-dependent growth. We find that ecological differences between haploid and diploid phases can lead to the evolution and maintenance of biphasic life cycles under a broad range of conditions. Parameter estimates derived from demographic data on a population of Gracilaria gracilis, a haploid-diploid red alga with an isomorphic alternation of generations, are used to demonstrate that an ecological explanation for haploid-diploidy is plausible even when there are only slight morphological differences among adults.

This study examines the reliability and validity of a measure to evaluate student field performance. Results demonstrated a consistent factor structure with excellent internal consistency, however, there was inadequate consistency between ratings of individual students in their first and second field education experiences. The measure had some predictive validity in that it could differentiate between students identified as having difficulty in Year 1 of the program, but not in Year 2. Scores were significantly associated with academic grades. Implications for future instrument development and the process of evaluation are considered.

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The LIM domain is a zinc-binding amino acid motif that characterizes various proteins which function in protein-protein interactions and transcriptional regulation. Expression patterns of several LIM protein genes are compatible with roles in vertebrate CNS development, but little is known about the expression, regulation, or function of LIM proteins in the mature CNS. Lmo1, Lmo2, and Lmo3 are LIM-only genes originally identified as putative oncogenes that have been implicated in the control of cell differentiation and are active during CNS development. Using in situ hybridization for mRNA and immunohistochemical detection of reporter protein expression in transgenic mice, we found that Lmo1, Lmo2, and Lmo3 show individually unique but partially overlapping patterns of expression in several regions of the adult mouse forebrain, including hippocampus, caudate putamen, medial habenula, thalamus, amygdala, olfactory bulb, hypothalamus, and cerebral cortex. In the hippocampal formation, Lmo1, Lmo2, and Lmo3 show different combinatorial patterns of expression levels in CA pyramidal and dentate granule neurons, and Lmo1 is present in topographically restricted subpopulations of astrocytes. Kainic acid-induced limbic seizures differentially regulated Lmo1, Lmo2, and Lmo3 mRNA levels in hippocampal pyramidal and granule neurons, such that Lmo1 mRNA increased, whereas Lmo2 and Lmo3 mRNAs decreased significantly, with maximal changes at 6 hr after seizure onset and return to baseline by 24 hr. These findings show that Lmo1, Lmo2, and Lmo3 continue to be expressed in the adult mammalian CNS in a cell type-specific manner, are differentially regulated by neuronal activity, and may thus be involved in cell phenotype-specific regulatory functions.