Research reveals that inducing empathy for a member of a stigmatized group can improve attitudes toward the group as a whole. But do these more positive attitudes translate into action on behalf of the group? Results of an experiment suggested an affirmative answer to this question. Undergraduates first listened to an interview with a convicted heroin addict and dealer; they were then given a chance to recommend allocation of Student Senate funds to an agency to help drug addicts. (The agency would not help the addict whose interview they heard.) Participants induced to feel empathy for the addict allocated more funds to the agency. Replicating past results, these participants also reported more positive attitudes toward people addicted to hard drugs. In addition, an experimental condition in which participants were induced to feel empathy for a fictional addict marginally increased action on behalf of, and more positive attitudes toward, drug addicts.

Hox and Cdx transcription factors regulate embryonic positional identities. Cdx mutant mice display posterior body truncations of the axial skeleton, neuraxis, and caudal urorectal structures. We show that trunk Hox genes stimulate axial extension, as they can largely rescue these Cdx mutant phenotypes. Conversely, posterior (paralog group 13) Hox genes can prematurely arrest posterior axial growth when precociously expressed. Our data suggest that the transition from trunk to tail Hox gene expression successively regulates the construction and termination of axial structures in the mouse embryo. Thus, Hox genes seem to differentially orchestrate posterior expansion of embryonic tissues during axial morphogenesis as an integral part of their function in specifying head-to-tail identity. In addition, we present evidence that Cdx and Hox transcription factors exert these effects by controlling Wnt signaling. Concomitant regulation of Cyp26a1 expression, restraining retinoic acid signaling away from the posterior growth zone, may likewise play a role in timing the trunk-tail transition.

The growth hormone receptor (GHR) is a critical regulator of postnatal growth and metabolism. However, the GHR signaling domains and pathways that regulate these processes in vivo are not defined. We report the first knock-in mouse models with deletions of specific domains of the receptor that are required for its in vivo actions. Mice expressing truncations at residue m569 (plus Y539/545-F) and at residue m391 displayed a progressive impairment of postnatal growth with receptor truncation. Moreover, after 4 months of age, marked male obesity was observed in both mutant 569 and mutant 391 and was associated with hyperglycemia. Both mutants activated hepatic JAK2 and ERK2, whereas STAT5 phosphorylation was substantially decreased for mutant 569 and absent from mutant 391, correlating with loss of IGF-1 expression and reduction in growth. Microarray analysis of these and GHR؊/؊ mice demonstrated that particular signaling domains are responsible for the regulation of different target genes and revealed novel actions of growth hormone. These mice represent the first step in delineating the domains of the GHR regulating body growth and composition and the transcripts associated with these domains.Over the last decade, extensive in vitro studies have identified signaling pathways triggered by growth hormone receptor (GHR) activation and the sequence motifs within the conserved cytoplasmic domain of the receptor that are required to initiate these pathways. These studies have established the critical signaling role of JAK2 tyrosine kinase, which is recruited to the trimeric GHR2:GH complex at the box 1/2 motif (9). Hormone binding initiates JAK2 transphosphorylation and activation, resulting in phosphorylation of critical tyrosines within the cytoplasmic domain of the GHR, as well as other direct JAK2 substrates such as IRS-1 and -2. The distal cytoplasmic phosphotyrosines of GHR have been shown to recruit signal transducer and activator of transcription 5 (STAT5) and other proteins through SH2-domain interactions, whereas the proximal JAK2 activation domain is responsible for ERK1/2 and phosphatidylinositol 3-kinase (PI 3-kinase) activation (30), although it has been claimed that residues distal to m390 are required for ERK1/2 activation (residue 390, mouse sequence numbers given throughout) (38). There is some dispute regarding the distal tyrosine residues used to recruit STAT5 for activation, notably in relation to tyrosine m498 (8, 33); moreover, it has been claimed that tyrosines m341 and m346, proximal to boxes 1 and 2, may also generate active STAT5 (31).In vitro studies have identified other signaling elements within the distal region of the GHR cytoplasmic domain, for example, a JAK2-independent calcium signaling element between residues m465 and m517 (30). SHP2 phosphatase can have a dual role when bound to the cytoplasmic domain of the GHR. It binds primarily to m606 to attenuate JAK2-STAT5 signaling but can also serve as an adaptor protein (30). GHdriven activation of STAT5 can also be attenuated by suppres...

GH is generally believed to signal exclusively through Janus tyrosine kinases (JAK), particularly JAK2, leading to activation of signal transducers and activators of transcription (STAT), ERK and phosphatidylinositol 3-kinase pathways, resulting in transcriptional regulation of target genes. Here we report the creation of targeted knock-in mice wherein the Box1 motif required for JAK2 activation by the GH receptor (GHR) has been disabled by four Pro/Ala mutations. These mice are unable to activate hepatic JAK2, STAT3, STAT5, or Akt in response to GH injection but can activate Src and ERK1/2. Their phenotype is identical to that of the GHR(-/-) mouse, emphasizing the key role of JAK2 in postnatal growth and the minimization of obesity in older males. In particular, they show dysregulation of the IGF-I/IGF-binding protein axis at transcript and protein levels and decreased bone length. Because no gross phenotypic differences were evident between GHR(-/-) and Box1 mutants, we undertook transcript profiling in liver from 4-month-old males. We compared their transcript profiles with our 391-GHR truncated mice, which activate JAK2, ERK1/2, and STAT3 in response to GH but not STAT5a/b. This has allowed us for the first time to identify in vivo Src/ERK-regulated transcripts, JAK2-regulated transcripts, and those regulated by the distal part of the GHR, particularly by STAT5.