Genome evolution in yeasts

Identifying the mechanisms of eukaryotic genome evolution by comparative genomics is often complicated by the multiplicity of events that have taken place throughout the history of individual lineages, leaving only distorted and superimposed traces in the genome of each living organism. The hemiascomycete yeasts, with their compact genomes, similar lifestyle and distinct sexual and physiological properties, provide a unique opportunity to explore such mechanisms. We present here the complete, assembled genome sequences of four yeast species, selected to represent a broad evolutionary range within a single eukaryotic phylum, that after analysis proved to be molecularly as diverse as the entire phylum of chordates. A total of approximately 24,200 novel genes were identified, the translation products of which were classified together with Saccharomyces cerevisiae proteins into about 4,700 families, forming the basis for interspecific comparisons. Analysis of chromosome maps and genome redundancies reveal that the different yeast lineages have evolved through a marked interplay between several distinct molecular mechanisms, including tandem gene repeat formation, segmental duplication, a massive genome duplication and extensive gene loss.     

VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche

The cellular and molecular mechanisms by which a tumour cell undergoes metastasis to a predetermined location are largely unknown. Here we demonstrate that bone marrow-derived haematopoietic progenitor cells that express vascular endothelial growth factor receptor 1 (VEGFR1; also known as Flt1) home to tumour-specific pre-metastatic sites and form cellular clusters before the arrival of tumour cells. Preventing VEGFR1 function using antibodies or by the removal of VEGFR1(+) cells from the bone marrow of wild-type mice abrogates the formation of these pre-metastatic clusters and prevents tumour metastasis, whereas reconstitution with selected Id3 (inhibitor of differentiation 3)-competent VEGFR1+ cells establishes cluster formation and tumour metastasis in Id3 knockout mice. We also show that VEGFR1+ cells express VLA-4 (also known as integrin alpha4beta1), and that tumour-specific growth factors upregulate fibronectin--a VLA-4 ligand--in resident fibroblasts, providing a permissive niche for incoming tumour cells. Conditioned media obtained from distinct tumour types with unique patterns of metastatic spread redirected fibronectin expression and cluster formation, thereby transforming the metastatic profile. These findings demonstrate a requirement for VEGFR1+ haematopoietic progenitors in the regulation of metastasis, and suggest that expression patterns of fibronectin and VEGFR1+VLA-4+ clusters dictate organ-specific tumour spread.     

Therapeutic and immunologic effects of iodoacetate in mature AKR mice

Résumé A des souris AKR leucémiques on administre un total de 5 injections de sulfhydryle inhibiteur, iodoacétate, à 10 jours d'intervalle. Ce régime produit une augmentation de survivance moyenne de 15 jours par rapport au groupe témoin. 40% des souris traitées vivent delà de la période d'expérimentation. Chez certaines souris traitées, on constate l'augemtation statistiquement assez importante des nombres totaux de cellules spléniques formatrices de plaquettes à tous les stades d'expérimentation.

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Supported in part by Grant No. 3362-Al from The Ohio Division of The American Cancer Society and Grant No. CA-13752-01 from The National Cancer Institute.     

An electron microscopic observation on diplococcus-shaped vesicles in papillary muscle of rat heart

Zusammenfassung Vesikelartige Gebilde wurden in Papillarmuskeln von Ratten beobachtet. Diese wie Diplokokken aussehenden Doppelvesikel lagen an der Zelloberfläche, innerhalb der transversalen Tubuli und im Zwischenraum der Glanzstreifen. Die Ergebnisse lassen eine enge Beziehung zwischen diesen diplokokkenartigen Vesikeln und den sogenannten Zystisomen vermuten.     

Regulation of lymphokine production in peripheral blood mononuclear cell cultures

Summary An increase in the production of macrophage migration inhibitory factor, chemotactic factor for neutrophils, and skin reactive factor, was observed in lymphocyte cultures if the cells were allowed to age in culture for 24 h. The increased lymphokine production was reduced by adding concanavalin A-stimulated and mitomycin C-treated suppressor cells. It is suggested that the lymphokine production could be regulated by suppressive mononuclear cells.This work was supported by the Scientific Research Council, Ministry of Health, Hungary (Code No. 421 0304011/S).     

Phospholipid alterations in liver and serum of rabbits treated with diphtheria toxin

Riassunto I fosfolipidi del siero di conigli a digiuno, trattati con tossina difterica per 15 ore, diminuiscono: questa diminuzione è a carico sorpattutto della frazione lecitinica. Le cause di questo comportamento sono brevemente discusse.

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The present research has been supported by a grant from the C.N.R. Roma (Italy).     

Cryptomare magmatism 4.35 Gyr ago recorded in lunar meteorite Kalahari 009

The origin and evolution of the Moon remain controversial, with one of the most important questions for lunar evolution being the timing and duration of basaltic (mare) magmatism. Here we report the result of ion microprobe U-Pb dating of phosphates in a lunar meteorite, Kalahari 009, which is classified as a very-low-Ti mare-basalt breccia. In situ analyses of five phosphate grains, associated with basaltic clasts, give an age of 4.35 +/- 0.15 billion years. These ancient phosphate ages are thought to represent the crystallization ages of parental basalt magma, making Kalahari 009 one of the oldest known mare basalts. We suggest that mare basalt volcanism on the Moon started as early as 4.35 Gyr ago, relatively soon after its formation and differentiation, and preceding the bulk of lunar volcanism which ensued after the late heavy bombardment around 3.8-3.9 Gyr (refs 7 and 8). Considering the extremely low abundances of incompatible elements such as thorium and the rare earth elements in Kalahari 009 (ref. 9) and recent remote-sensing observations illustrating that the cryptomaria tend to be of very-low-Ti basalt type, we conclude that Kalahari 009 is our first sample of a very-low-Ti cryptomare from the Moon.