Cytoglobin: biochemical,functional and clinical perspective of the newest member of the globin family

Since the discovery of cytoglobin (Cygb) a decade ago, growing amounts of data have been gathered to characterise Cygb biochemistry, functioning and implication in human pathologies. Its molecular roles remain under investigation, but nitric oxide dioxygenase and lipid peroxidase activities have been demonstrated. Cygb expression increases in response to various stress conditions including hypoxia, oxidative stress and fibrotic stimulation. When exogenously overexpressed, Cygb revealed cytoprotection against these factors. Cygb was shown to be upregulated in fibrosis and neurodegenerative disorders and downregulated in multiple cancer types. CYGB was also found within the minimal region of a hereditary tylosis with oesophageal cancer syndrome, and its expression was reduced in tylotic samples. Recently, Cygb has been shown to inhibit cancer cell growth in vitro, thus confirming its suggested tumour suppressor role. This article aims to review the biochemical and functional aspects of Cygb, its involvement in various pathological conditions and potential clinical utility.     

Corneal avascularity is due to soluble VEGF receptor-1

Corneal avascularity-the absence of blood vessels in the cornea-is required for optical clarity and optimal vision, and has led to the cornea being widely used for validating pro- and anti-angiogenic therapeutic strategies for many disorders. But the molecular underpinnings of the avascular phenotype have until now remained obscure and are all the more remarkable given the presence in the cornea of vascular endothelial growth factor (VEGF)-A, a potent stimulator of angiogenesis, and the proximity of the cornea to vascularized tissues. Here we show that the cornea expresses soluble VEGF receptor-1 (sVEGFR-1; also known as sflt-1) and that suppression of this endogenous VEGF-A trap by neutralizing antibodies, RNA interference or Cre-lox-mediated gene disruption abolishes corneal avascularity in mice. The spontaneously vascularized corneas of corn1 and Pax6+/- mice and Pax6+/- patients with aniridia are deficient in sflt-1, and recombinant sflt-1 administration restores corneal avascularity in corn1 and Pax6+/- mice. Manatees, the only known creatures uniformly to have vascularized corneas, do not express sflt-1, whereas the avascular corneas of dugongs, also members of the order Sirenia, elephants, the closest extant terrestrial phylogenetic relatives of manatees, and other marine mammals (dolphins and whales) contain sflt-1, indicating that it has a crucial, evolutionarily conserved role. The recognition that sflt-1 is essential for preserving the avascular ambit of the cornea can rationally guide its use as a platform for angiogenic modulators, supports its use in treating neovascular diseases, and might provide insight into the immunological privilege of the cornea.     

Migration of lymphocytes through the endothelium of venules in experimental allergic neuritis

Zusammenfassung Bei der experimentellen allergischen Neuritis verlassen die Lymphozyten das zirkulierende Blut der Venolen der peripheren Nerven, indem sie eher durch die als zwischen den Endothelzellen austreten. Der Durchtritt durch das Zytoplasma der Endothelzellen ist ein Beispiel von Emperipolesis.

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Supported by parts by NIH grant No. NB-03789-05, Inst. grant No. FRO5486-04, and a grant from the Swedish Medical Research Council. I thank Mr.L. Cherkas for help with the photography.     

Cloned pigs produced by nuclear transfer from adult somatic cells

Since the first report of live mammals produced by nuclear transfer from a cultured differentiated cell population in 1995 (ref. 1), successful development has been obtained in sheep, cattle, mice and goats using a variety of somatic cell types as nuclear donors. The methodology used for embryo reconstruction in each of these species is essentially similar: diploid donor nuclei have been transplanted into enucleated MII oocytes that are activated on, or after transfer. In sheep and goat pre-activated oocytes have also proved successful as cytoplast recipients. The reconstructed embryos are then cultured and selected embryos transferred to surrogate recipients for development to term. In pigs, nuclear transfer has been significantly less successful; a single piglet was reported after transfer of a blastomere nucleus from a four-cell embryo to an enucleated oocyte; however, no live offspring were obtained in studies using somatic cells such as diploid or mitotic fetal fibroblasts as nuclear donors. The development of embryos reconstructed by nuclear transfer is dependent upon a range of factors. Here we investigate some of these factors and report the successful production of cloned piglets from a cultured adult somatic cell population using a new nuclear transfer procedure.     

Evolutionary origins of vertebrate appendicular muscle

The evolution of terrestrial tetrapod species heralded a transition in locomotor strategies. While most fish species use the undulating contractions of the axial musculature to generate propulsive force, tetrapods also rely on the appendicular muscles of the limbs to generate movement. Despite the fossil record generating an understanding of the way in which the appendicular skeleton has evolved to provide the scaffold for tetrapod limb musculature, there is, by contrast, almost no information as to how this musculature arose. Here we examine fin muscle formation within two extant classes of fish. We find that in the teleost, zebrafish, fin muscles arise from migratory mesenchymal precursor cells that possess molecular and morphogenetic identity with the limb muscle precursors of tetrapod species. Chondrichthyan dogfish embryos, however, use the primitive mechanism of direct epithelial somitic extensions to derive the muscles of the fin. We conclude that the genetic mechanism controlling formation of tetrapod limb muscles evolved before the Sarcopterygian radiation.     

Synthesis of rhodotorucine A,the inducing factor of mating tube formation ofRhodosporidium toruloides

Summary The inducing factor of mating tube formation ofRhodosporidium turuloides, named rhodotorucine A (H-Tyr-Pro-Glu-Ile-Ser-Trp-Thr-Arg-Asn-Gly-Cys(S-farnesyl)-OH), has been synthesized to confirm the structure proposed for the natural lipopeptide. The synthetic S-farnesyl undecapeptide has identical Rf values on TLC using several different solvents, and also the same biological activity as the natural hormone.Acknowledgments. We wish to express our thanks to Drs E. Ohmura, M. Nishikawa and M. Yoneda of Takeda Chemical Industries and Dr I. Banno of Institute for Fermentation, Osaka, for their encouragement throughout this work.     

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).     

Tumeurs mammaires et leucémies dans une nouvelle souche de souris (PS): Etude au microscope électronique

Summary In the recently isolated Mouriquand strain of mice, virus-like particles of the A and B type are abundant in mammary tumours, and fewer particles of the C type are present in leukaemic and non-leukaemic organs. In one animal all three kinds of particles have been shown. Striking cytological features of the mammary tumours are described.