Phosphoinositide 3-Kinase p110�� Regulates Integrin ��IIb��3 Avidity and the Cellular Transmission of Contractile Forces

Phosphoinositide (PI) 3-kinase (PI3K) signaling processes play an important role in regulating the adhesive function of integrin α_IIbβ₃, necessary for platelet spreading and sustained platelet aggregation. PI3K inhibitors are effective at reducing platelet aggregation and thrombus formation in vivo and as a consequence are currently being evaluated as novel antithrombotic agents. PI3K regulation of integrin α_IIbβ₃ activation (affinity modulation) primarily occurs downstream of G_i-coupled and tyrosine kinase-linked receptors linked to the activation of Rap1b, AKT, and phospholipase C. In the present study, we demonstrate an important role for PI3Ks in regulating the avidity (strength of adhesion) of high affinity integrin α_IIbβ₃ bonds, necessary for the cellular transmission of contractile forces. Using knock-out mouse models and isoform-selective PI3K inhibitors, we demonstrate that the Type Ia p110β isoform plays a major role in regulating thrombin-stimulated fibrin clot retraction in vitro. Reduced clot retraction induced by PI3K inhibitors was not associated with defects in integrin α_IIbβ₃ activation, actin polymerization, or actomyosin contractility but was associated with a defect in integrin α_IIbβ₃ association with the contractile cytoskeleton. Analysis of integrin α_IIbβ₃ adhesion contacts using total internal reflection fluorescence microscopy revealed an important role for PI3Ks in regulating the stability of high affinity integrin α_IIbβ₃ bonds. These studies demonstrate an important role for PI3K p110β in regulating the avidity of high affinity integrin α_IIbβ₃ receptors, necessary for the cellular transmission of contractile forces. These findings may provide new insight into the potential antithrombotic properties of PI3K p110β inhibitors.     

Molecular cloning and characterization of the rat liver IL-6 signal transducing molecule, gp130.

Interleukin-6 (IL-6) is a multifunctional cytokine that exerts its effects on different target cells by interacting with a specific receptor. This interaction leads to the association and activation of a second membrane glycoprotein, gp130, which is the IL-6 signal transducing molecule. The nucleotide sequence of gp130 from a human B-cell line has been reported. We report here the cloning and sequence analysis of the gp130 molecule derived from rat liver. Comparison of gp130 molecules from the different species and cell types reveals 78% overall amino acid homology and 94% identity in the growth factor signaling domain. Two gp130 mRNA species, a moderately abundant species of 7.5 kb and a lesser one of 9.0 kb, were present in rat hepatocytes. Ribonuclease protection analyses demonstrated the presence of gp130 mRNA in four different nontransformed cell types: hepatocytes, astrocytes, fibroblasts, and endothelial cells. The sequences between both gp130s in the different cell types are quite similar, supporting the prediction that the different responses initiated by IL-6 on different target cells are modulated by cell-specific proteins distal to the activated gp130 molecule.     

The theropod furcula

The furcula is a structure formed by the midline fusion of the clavicles. This is the element which is unique to theropods and is important for understanding the link between birds and other theropods. New specimens from basal theropods suggest that the furcula appeared very early in theropod history. We review furcula development, function, and morphology, as well as the anatomical terminology applied to it. Furcular morphology is highly variable in crown‐group avians but is rather conserved among nonavian theropods. Here we review, or describe for the first time, the furculae in many nonavian theropods. Furculae occur in nearly all major clades of theropods, as shown by new theropod specimens from the Early Cretaceous of China and a close inspection of previously collected specimens. Informative phylogenetic characters pertaining to the furcula occur throughout Theropoda, though care should betake to consider taphonomic effects when describing furcular morphology. J. Morphol., 2009. © 2009 Wiley‐Liss, Inc.     

An Unusual Xylotheque with Plant Illustrations from Early Meiji Japan

An Unusual Xylotheque with Plant Illustrations from Early Meiji Japan. Two unusual wood collections, reported previously in the collections of the Botanical Museum at Berlin-Dahlem and the Royal Botanic Gardens, Kew, take the form of framed plant illustrations painted on boards made from the wood of the species illustrated. We present new finds of very similar wood collections in the Economic Botany Collection of the Harvard University Herbaria, a private collection in the U.K. (Loudon collection), and at the Koishikawa Botanical Garden of the University of Tokyo. A stamp on the reverse of the boards links all five collections to Chikusai Kato, an artist working at Tokyo University (now the University of Tokyo) in early Meiji Japan, under the direction of the preeminent nineteenth century Japanese botanist Keisuke Ito. New evidence from contemporary historical accounts indicates that more than 100 boards were ordered in June 1878 by Hiroyuki Katō, the first president of Tokyo University, most likely to support the early teaching of Western-influenced botanical science in Japan. However, while the boards had clear value for teaching, especially about useful plants, their unusual fusion of Western and Japanese influences also made them desirable craft objects that were collected and given as gifts during the early Meiji era.     

Genetic regulation of lipopolysaccharide-induced interleukin 1 production by murine peritoneal macrophages

The production of IL 1 by LPS-stimulated peritoneal macrophages from inbred mouse strains was studied. Macrophages from A/J (A) mice were deficient in IL 1 production, when compared with high IL 1-producing strains, including C57BL/6J (B). The difference between A and B macrophages was maintained over a wide LPS concentration range and throughout a 72-hr incubation period. Because of these differences, it was possible to investigate the mechanisms regulating IL 1 production by applying techniques of genetic analysis by using recombinant inbred (RI) strains derived from the A and B progenitors. A strain distribution pattern (SDP) of IL 1 production (low/high response) was obtained with the use of 15 AXB/BXA RI strains. This suggested the presence of a major gene locus controlling the production of IL 1 in response to LPS stimulation, with allelic differences presumably resulting in deficient or efficient IL 1 production. In addition, there appeared to be one or more other loci involved in determining the magnitude of the IL 1 response to LPS in the responder mice. The IL 1 response did not appear to be linked to the major histocompatibility complex, since B10.A mice (which share the same H-2a haplotype as A/J) were efficient IL 1 producers. There did not appear to be any correlation between the degree of IL 1 production and the magnitude of the peritoneal macrophage inflammatory response, or between IL 1 production and LPS responsiveness (as determined by splenocyte proliferation). SDP analysis also indicated that the IL 1 response was not linked to macrophage tumoricidal activity. A comparison of the SDP for IL 1 production with a library of SDP for other known genetic waits suggested linkage with at least four loci on chromosome 1.     

Photographing worship: Ethnographic study of children's participation in acts of worship

This article reports the uses of photography in the Religious Education and Community Project, Coventry, England. It shows how ethnographic fieldwork and the development of curriculum materials for religious education in Britain are being conducted as phases of an integrated process. The photographic record, it is argued, is intrinsic both to eliciting data from members of the communities under study and in the sensitizing and informing of both pupils and educators. Furthermore not only the photographs themselves but also the differing reactions of specific communities to the prospect of being photographed during worship need analysis and can provide insights of value to religious educators in understanding the relation of cultural norms and theological emphases. As an illustration the responses of Christians to the ethnographer's requests to photograph the rite of Holy Communion are considered.