The roles of WRN and BLM RecQ helicases in the Alternative Lengthening of Telomeres

Approximately 10% of all cancers, but a higher proportion of sarcomas, use the recombination-based alternative lengthening of telomeres (ALT) to maintain telomeres. Two RecQ helicase genes, BLM and WRN, play important roles in homologous recombination repair and they have been implicated in telomeric recombination activity, but their precise roles in ALT are unclear. Using analysis of sequence variation present in human telomeres, we found that a WRN– ALT+ cell line lacks the class of complex telomere mutations attributed to inter-telomeric recombination in other ALT+ cell lines. This suggests that WRN facilitates inter-telomeric recombination when there are sequence differences between the donor and recipient molecules or that sister-telomere interactions are suppressed in the presence of WRN and this promotes inter-telomeric recombination. Depleting BLM in the WRN– ALT+ cell line increased the mutation frequency at telomeres and at the MS32 minisatellite, which is a marker of ALT. The absence of complex telomere mutations persisted in BLM-depleted clones, and there was a clear increase in sequence homogenization across the telomere and MS32 repeat arrays. These data indicate that BLM suppresses unequal sister chromatid interactions that result in excessive homogenization at MS32 and at telomeres in ALT+ cells.     

Hierarchical down-modulation of hemopoietic growth factor receptors

Granulocytes and macrophages can be produced in vitro when progenitor cells from mouse bone marrow are stimulated by any of four distinct colony stimulating factors, Multi-CSF (IL-3), GM-CSF, G-CSF, and M-CSF (CSF-1). At 0 degrees C the four CSFs do not cross-compete for binding to bone marrow cells, indicating that each has a specific cell surface receptor. However, at 21 degrees C or 37 degrees C, Multi-CSF inhibits binding of the other three CSFs and GM-CSF inhibits binding of G-CSF and M-CSF. Rather than competing directly for receptor binding, the binding of Multi-CSF, GM-CSF, or G-CSF to their own receptor induces the down-modulation (and thus activation) of other CSF receptors at 37 degrees C. The pattern and potency of down-modulation activity exhibited by each type of CSF parallels the pattern and potency of its biological activity. We propose a model in which the biological interactions of the four CSFs are explained by their ability to down-modulate and activate lineage-specific receptors.     

Immunological study of a hemophiliac treated according to the Bonn protocol for 2 1/2 years

A major haemophiliac A, 27 years old, has been treated during 30 months, with high dosage of imported Factor VIII, in order to reduce the titer of a F VIII antibody. A good clinical result has been obtained. No sign of immunodeficiency has been observed. Normal values were obtained for T4/T8, ratio B2 microglobulin and no antibody was detected against the LAV virus isolated from cases of AIDS.     

Contributo alla conoscenza del contingente nervoso corneale

Riassunto Nella cornea del ratto, in tutta quella parte del parenchima che è al margine con la sclerotica, esistono due cospicue formazioni a plesso, una vascolare e l'altra nervosa, in stretto reciproco rapporto topografico e verosimilmente anche funzionale.Il plesso nervoso è formato da fibre di varia provenienza, mieliniche ed amieliniche, fra loro mescolate ed anastomizzate, soprattutto mediante la rete diffusa alla quale danno origine.È molto probabile che a queste due formazioni, vascolare e nervosa, non sia riservato il solo compito di assicurare la nutrizione della cornea; ma penso che esse non siano estranee al meccanismo regolatore dell'umore acqueo.

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Zusammenfassung Der Verfasser hat mit der Bielschowsky-Grosschen Methode und vor allem mit der Schwarzreaktion von Golgi in Epymis norv. die angehäufte Zahl von Nerven studiert, die im Zusammenhang mit dem Hornhautrand stehen und von denen weder die Topographie noch ihre Bedeutung sonderlich bekannt war. Indem der Verfasser diese Methoden mit der Injektion des Blutgefäßsystems verband, hat er festgestellt, daß der plexiforme Nervenapparat enge topographische und funktionelle Beziehungen zu dem sich ringförmig in der gleichen Zone erstreckenden Gefäßplexus hat.Der Verfasser legt außerdem klar, daß dieser vasculonervöse Plexus zur Hornhaut und nicht zu anderen Bildungen gehört. Er schließt ferner, daß diesem angesichts seiner großen Entwicklung eine bemerkenswertere Aufgabe zukommt als jene, lediglich die Ernährung der Hornhaut zu sichern und daß er ein Teil des sinnreichen Regulationsmechanismus des Kammerwassers sei.

     

An abnormal terminal X-Y interchange accounts for most but not all cases of human XX maleness

To determine if human XX maleness results from an abnormal chromosomal X-Y interchange, we studied the inheritance of the paternal pseudoautosomal region in nine patients. Those six patients in whom Y-specific DNA was found (Y(+)) inherited the entire pseudoautosomal region from the paternal Y chromosome and lost that of the paternal X chromosome. Moreover, in three Y(+) cases, we observed the deletion of a paternal Xp locus tightly linked to the pseudoautosomal region. These results definitively show that an abnormal and terminal X-Y interchange during paternal meiosis causes Y(+)XX maleness. In contrast, no abnormal X-Y interchange was observed in any of the three Y(-) cases analyzed, suggesting that maleness can occur in the absence of any Y-specific DNA.     

Structural studies on the murine granulocyte colony-stimulating factor

Granulocyte-colony stimulating factor (G-CSF) is a glycoprotein hemopoietic growth factor which regulates the production of granulocytes and macrophages. Reversed-phase microbore high-performance liquid chromatography was employed to purify a number of tryptic and Staphylococcus aureus V8 proteinase peptides generated from approximately 400 pmol G-CSF purified from medium conditioned by lungs from mice previously injected with endotoxin. N-Terminal amino-acid sequence analyses were performed on the parent polypeptide and on four tryptic peptides and one Staphylococcus aureus V8 protease peptide, yielding 68 unique amino-acid assignments; this corresponds to approximately 38% of the molecule.