Proton-sensing G-protein-coupled receptors

Blood pH is maintained in a narrow range around pH 7.4 mainly through regulation of respiration and renal acid extrusion. The molecular mechanisms involved in pH homeostasis are not completely understood. Here we show that ovarian cancer G-protein-coupled receptor 1 (OGR1), previously described as a receptor for sphingosylphosphorylcholine, acts as a proton-sensing receptor stimulating inositol phosphate formation. The receptor is inactive at pH 7.8, and fully activated at pH 6.8-site-directed mutagenesis shows that histidines at the extracellular surface are involved in pH sensing. We find that GPR4, a close relative of OGR1, also responds to pH changes, but elicits cyclic AMP formation. It is known that the skeleton participates in pH homeostasis as a buffering organ, and that osteoblasts respond to pH changes in the physiological range, but the pH-sensing mechanism operating in these cells was hitherto not known. We detect expression of OGR1 in osteosarcoma cells and primary human osteoblast precursors, and show that these cells exhibit strong pH-dependent inositol phosphate formation. Immunohistochemistry on rat tissue sections confirms the presence of OGR1 in osteoblasts and osteocytes. We propose that OGR1 and GPR4 are proton-sensing receptors involved in pH homeostasis.     

Horsetails and ferns are a monophyletic group and the closest living relatives to seed plants

Most of the 470-million-year history of plants on land belongs to bryophytes, pteridophytes and gymnosperms, which eventually yielded to the ecological dominance by angiosperms 90 Myr ago. Our knowledge of angiosperm phylogeny, particularly the branching order of the earliest lineages, has recently been increased by the concurrence of multigene sequence analyses. However, reconstructing relationships for all the main lineages of vascular plants that diverged since the Devonian period has remained a challenge. Here we report phylogenetic analyses of combined data--from morphology and from four genes--for 35 representatives from all the main lineages of land plants. We show that there are three monophyletic groups of extant vascular plants: (1) lycophytes, (2) seed plants and (3) a clade including equisetophytes (horsetails), psilotophytes (whisk ferns) and all eusporangiate and leptosporangiate ferns. Our maximum-likelihood analysis shows unambiguously that horsetails and ferns together are the closest relatives to seed plants. This refutes the prevailing view that horsetails and ferns are transitional evolutionary grades between bryophytes and seed plants, and has important implications for our understanding of the development and evolution of plants.     

Rabbit immunization to xenogeneic red blood cells following anterior eye chamber inoculation

Summary Inoculation of human red blood cells (HRBC) into the anterior chamber of the eye (AC) of rabbits effectively stimulazed systemic antibody production. Intraocular (i.o.) inoculation was observed to be more effective a route of immunization than i.v. or i.m. inoculation of antigen. These results contradict the accepted belief that the AC is an immunologically privileged site in the body.     

Evaluation of the maternal role in survival of suckling mice

Zusammenfassung Das Überleben der von der eigenen Mutter und von stammesfremden «Ammen» gesäugten Jungen wurde untersucht an Mäusen der Stämme AKR/Sp, PL/Sp und C57BL/Sp. Die Ergebnisse zeigen, dass die genetische Herkunft der Säuglinge wie auch andere, nicht genetisch bedingte Einflüsse der Mutter auf die Jungen in utero für das Überleben der Jungen ausschlaggebend ist.

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This investigation was supported in part by Public Health Service Research Grants Nos. CA 02151, CA 02903 and CA 02624 from the National Cancer Institute, and in part by an institutional grant to the Detroit Institute of Cancer Research from the United Foundation of Greater Detroit allocated through the Michigan Cancer Foundation.