Formation of haematopoietic microenvironment and haematopoietic stem cells from single human bone marrow stem cells.

Haematopoietic stem cells are a population of cells capable both of self renewal and of differentiation into a variety of haematopoietic lineages. Enrichment techniques of human haematopoietic stem cells have used the expression of CD34, present on bone marrow progenitor cells. But most CD34+ bone marrow cells are committed to their lineage, and more recent efforts have focused on the precise characterization of the pluripotent subset of CD34+ cells. Here we report the characterization of two distinct subsets of pluripotent stem cells from human fetal bone marrow, a CD34+, HLA-DR+, CD38- subset that can differentiate into all haematopoietic lineages, and a distinct more primitive subset, that is CD34+, HLA-DR-, CD38-, that can differentiate into haematopoietic precursors and stromal cells capable of supporting the differentiation of these precursors. These data represent, to our knowledge, the first identification of a single cell capable of reconstituting the haematopoietic cells and their associated bone marrow microenvironment.     

Regulation of the cardiac sodium pump

In cardiac muscle, the sarcolemmal sodium/potassium ATPase is the principal quantitative means of active transport at the myocyte cell surface, and its activity is essential for maintaining the trans-sarcolemmal sodium gradient that drives ion exchange and transport processes that are critical for cardiac function. The 72-residue phosphoprotein phospholemman regulates the sodium pump in the heart: unphosphorylated phospholemman inhibits the pump, and phospholemman phosphorylation increases pump activity. Phospholemman is subject to a remarkable plethora of post-translational modifications for such a small protein: the combination of three phosphorylation sites, two palmitoylation sites, and one glutathionylation site means that phospholemman integrates multiple signaling events to control the cardiac sodium pump. Since misregulation of cytosolic sodium contributes to contractile and metabolic dysfunction during cardiac failure, a complete understanding of the mechanisms that control the cardiac sodium pump is vital. This review explores our current understanding of these mechanisms.     

Striated inclusions and defective mitochondria in the restricted form of the ‘amycelial’ mutant ofNeurospora crassa

Summary The cytoplasm of the restrictive form of the amycelial mutant ofNeurospora crassa, growing on sucrosemedium, contains paracrystalline, microfilamentous inclusions and mitochondria with internal membranous whorls lacking in acetate-grown cultures.The support of the Fonds national suisse de la recherche scientifique is gratefully acknowledged.     

The role of repair in radiobiology

Summary Apart from cancer and mutation induction, radiobiological effects on mammals are mostly attributable to cell death, defined as loss of proliferative capacity. Survival curves relate retention of that capacity to radiation dose, and often manifest a quasi-threshold (shoulder). The shoulder is attributable to an initial mechanism of repair (Q-repair) which is gradually depleted as dose increases. Another form of repair, which is not depleted (P-repair), increases the dose required to deliver an average of one lethal event per cell (dose D₀). Neither form of repair can unambiguously be linked with repair of defects in isolated DNA. An important initial lesion may well be disruption of the complex structural relationship between the DNA, nuclear membrane and associated proteins. One form of P-repair may be restoration of that structural relationship.     

1-(substituted)benzyl-5-aminoimidazole-4-carboxamides are potent orally active inhibitors of Trypanosoma cruzi in mice

1-(Substituted)benzyl-5-aminoimidazole-4-carboxamides are potent orally active inhibitors of Trypanosoma cruzi infections in mice. The most active compounds are the 1-(4-chlorobenzyl)- and 1-(3,4-dichlorobenzyl)-analogs (L-153,094 [2] and L-153,153 [4], resp.) which are approximately 7-fold more potent upon oral administration than nifurtimox (Lampit) in suppressing parasite levels in the blood of mice with acute Trypanosoma cruzi infections.     

Chromosomal effects of adeno-associated virus vector integration.

Adeno-associated virus (AAV) vectors are currently being used in several clinical gene-therapy trials (see the NIH OBA Human Gene Transfer Clinical Trials Database); however, little is known about the chromosomal effects of vector integration. Here we report that integrated vector proviruses are associated with chromosomal deletions and other rearrangements and are frequently located on chromosome 19 (although not at the wildtype AAV integration site).     

The chromosomes ofMarmosa fuscata thomas,from northern Venezuela (Marsupialia,Didelphidae)

Resumen Los cromosomas deMarmosa fuscata (subgéneroMarmosops), estudiados por cultivo de tejidos en base a 4 individuos de la Cordillera de la Costa en el norte de Venezuela, resultaron diferir de los deMarmosa robinsoni sólo en el quinto y sexto par de autosomas, metacéntricos en la primera y subtelocéntricos en la segunda especie. Con todo, se encuentran mayores diferencias entre los cariotipos de estas 2 especies que entre los deM. robinsoni yCaluromys derbianus.     

Pitch discrimination in the minnow(Phoxinus laevis) at different temperature levels

Zusammenfassung Aus früheren Untersuchungen war bekannt, dass die Elritze (Phoxinus laevis) imstande ist, Töne nach ihrer Frequenz (Tonhöhe) zu unterscheiden, jedoch nur im Frequenzgebiet bis zu etwa 1260 Hz, nicht darüber (die obere Hörgrenze liegt bei etwa 5000 Hz). Es wurde geprüft, welchen Einfluss Wechsel der Temperatur auf die Lage dieser oberen Schwelle der Frequenzunterscheidung hat. Sie lag für die einzelnen Versuchstiere bei 16°C zwischen 800 und 1260 Hz; bei 25°C zwischen 1260 und 1420 Hz, also höher. Der Unterschied beruht nicht auf grösserer Lebhaftigkeit oder Reaktionsbereitschaft der Fische bei der höheren Temperatur. Das Ergebnis steht im Einklang mit der Vermutung, dass die Tonfrequenzunterscheidung bei Fischen nach dem «volley principle» (Wever) erfolgt.