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.     

The Effects of Temperature and Body Mass on Jump Performance of the Locust Locusta migratoria

Locusts jump by rapidly releasing energy from cuticular springs built into the hind femur that deform when the femur muscle contracts. This study is the first to examine the effect of temperature on jump energy at each life stage of any orthopteran. Ballistics and high-speed cinematography were used to quantify the energy, distance, and take-off angle of the jump at 15, 25, and 35°C in the locust Locusta migratoria. Allometric analysis across the five juvenile stages at 35°C reveals that jump distance (D; m) scales with body mass (M; g) according to the power equation D = 0.35M ^{0.17±0.08 (95% CI)}, jump take-off angle (A; degrees) scales as A = 52.5M ^0.00±0.06, and jump energy (E; mJ per jump) scales as E = 1.91M ^1.14±0.09. Temperature has no significant effect on the exponent of these relationships, and only a modest effect on the elevation, with an overall Q₁₀ of 1.08 for jump distance and 1.09 for jump energy. On average, adults jump 87% farther and with 74% more energy than predicted based on juvenile scaling data. The positive allometric scaling of jump distance and jump energy across the juvenile life stages is likely facilitated by the concomitant relative increase in the total length (L _f+t; mm) of the femur and tibia of the hind leg, L _f+t = 34.9M ^0.37±0.02. The weak temperature-dependence of jump performance can be traced to the maximum tension of the hind femur muscle and the energy storage capacity of the femur''s cuticular springs. The disproportionately greater jump energy and jump distance of adults is associated with relatively longer (12%) legs and a relatively larger (11%) femur muscle cross-sectional area, which could allow more strain loading into the femur''s cuticular springs. Augmented jump performance in volant adult locusts achieves the take-off velocity required to initiate flight.     

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.