Fibronectin peptide DRVPHSRNSIT and fibronectin receptor peptide DLYYLMDL arrest gastrulation ofRana pipiens

Gastrulation is characterized by dramatic cell migration which is thought to require the interaction of cell adhesion molecules with extracellular molecules. We have tested two novel peptides, a fibronectin peptide and a fibronectin receptor peptide, for their effects on gastrulation of the leopard frogRana pipiens. The fibronectin peptide DRVPHSRNSIT corresponds to residues 1373–1383 of the cell-binding domain of fibronectin; the receptor peptide DLYYLMDL corresponds to residues 124–131 of 1 subunit of a variety of integrins including 51. Either of these peptides significantly inhibited gastrulation after being microinjected into mid-blastulae. These results indicate that these sequences may correspond to the ligand/receptor interaction sites of fibronectin and its receptor(s).     

Lead potentiation of endotoxin lethality in rats: lack of effect of kininase inhibition.

Although lead and SQ20881 are potent in vitro inhibitors of kininase II activity, SQ20881 does not alter the sensitivity of rats to endotoxin. These results indicate that marked changes in plasma kininase activity do not contribute to endotoxin morbidity and that kininase inhibition is not the mechanism whereby lead ions sensitize rats to endotoxin.     

Two types of viruslike particles inDrosophila midgut

Résumé On a trouvé des particules hexagonales, comme des virus, de deux grandeurs, dans les cellules de la partie centrale de l'intestin de laDrosophile. Les particules les plus grosses étaient dans le cytoplasme et les plus petites dans le noyau. L'apparence de la distribution de ces particules sont en fonction de l'âge de la mouche.

---

---

Part of this work was supported by research grant No. AM 12818 of the National Institute of Arthritis and Metabolic Diseases.     

Exon capture analysis of G protein-coupled receptors identifies activating mutations in GRM3 in melanoma

G protein-coupled receptors (GPCRs), the largest human gene family, are important regulators of signaling pathways. However, knowledge of their genetic alterations is limited. In this study, we used exon capture and massively parallel sequencing methods to analyze the mutational status of 734 GPCRs in melanoma. This investigation revealed that one family member, GRM3, was frequently mutated and that one of its mutations clustered within one position. Biochemical analysis of GRM3 alterations revealed that mutant GRM3 selectively regulated the phosphorylation of MEK, leading to increased anchorage-independent growth and migration. Melanoma cells expressing mutant GRM3 had reduced cell growth and cellular migration after short hairpin RNA-mediated knockdown of GRM3 or treatment with a selective MEK inhibitor, AZD-6244, which is currently being used in phase 2 clinical trials. Our study yields the most comprehensive map of genetic alterations in the GPCR gene family.     

Lead potentiation of endotoxin lethality in rats: Lack of effect of kininase inhibition

Summary Although lead and SQ₂₀₈₈₁ are potent in vitro inhibitors of kininase II activity, SQ₂₀₈₈₁ does not alter the sensitivity of rats to endotoxin. These results indicate that marked changes in plasma kininase activity do not contribute to endotoxin morbility and that kininase inhibition is not the mechanism whereby lead ions sensitize rats to endotoxin.This investigation was supported by the Naval Medical Research and Development Command, NNMC, Department of the Navy, Research Task No. MR041.20.01.0435. The opinions and assertions contained herein are the private ones of the author, and are not to be construed as official or reflecting the views of the Navy Department or the naval service at large.The experiments reported herein were conducted according to the principles set forth in the Guide for the Care and Use of Laboratory Animals, Institute of Laboratory Animal Resources, National Research Council, DHEW Pub. No. (NIH) 74-23.     

Exome sequencing identifies GRIN2A as frequently mutated in melanoma

The incidence of melanoma is increasing more than any other cancer, and knowledge of its genetic alterations is limited. To systematically analyze such alterations, we performed whole-exome sequencing of 14 matched normal and metastatic tumor DNAs. Using stringent criteria, we identified 68 genes that appeared to be somatically mutated at elevated frequency, many of which are not known to be genetically altered in tumors. Most importantly, we discovered that TRRAP harbored a recurrent mutation that clustered in one position (p. Ser722Phe) in 6 out of 167 affected individuals (～4%), as well as a previously unidentified gene, GRIN2A, which was mutated in 33% of melanoma samples. The nature, pattern and functional evaluation of the TRRAP recurrent mutation suggest that TRRAP functions as an oncogene. Our study provides, to our knowledge, the most comprehensive map of genetic alterations in melanoma to date and suggests that the glutamate signaling pathway is involved in this disease.