The bipolar mitotic kinesin Eg5 moves on both microtubules that it crosslinks

During cell division, mitotic spindles are assembled by microtubule-based motor proteins. The bipolar organization of spindles is essential for proper segregation of chromosomes, and requires plus-end-directed homotetrameric motor proteins of the widely conserved kinesin-5 (BimC) family. Hypotheses for bipolar spindle formation include the 'push-pull mitotic muscle' model, in which kinesin-5 and opposing motor proteins act between overlapping microtubules. However, the precise roles of kinesin-5 during this process are unknown. Here we show that the vertebrate kinesin-5 Eg5 drives the sliding of microtubules depending on their relative orientation. We found in controlled in vitro assays that Eg5 has the remarkable capability of simultaneously moving at approximately 20 nm s(-1) towards the plus-ends of each of the two microtubules it crosslinks. For anti-parallel microtubules, this results in relative sliding at approximately 40 nm s(-1), comparable to spindle pole separation rates in vivo. Furthermore, we found that Eg5 can tether microtubule plus-ends, suggesting an additional microtubule-binding mode for Eg5. Our results demonstrate how members of the kinesin-5 family are likely to function in mitosis, pushing apart interpolar microtubules as well as recruiting microtubules into bundles that are subsequently polarized by relative sliding.     

Calcium triggers exit from meiosis II by targeting the APC/C inhibitor XErp1 for degradation

Vertebrate eggs awaiting fertilization are arrested at metaphase of meiosis II by a biochemical activity termed cytostatic factor (CSF). This activity inhibits the anaphase-promoting complex/cyclosome (APC/C), a ubiquitin ligase that triggers anaphase onset and mitotic/meiotic exit by targeting securin and M-phase cyclins for destruction. On fertilization a transient rise in free intracellular calcium causes release from CSF arrest and thus APC/C activation. Although it has previously been shown that calcium induces the release of APC/C from CSF inhibition through calmodulin-dependent protein kinase II (CaMKII), the relevant substrates of this kinase have not been identified. Recently, we characterized XErp1 (Emi2), an inhibitor of the APC/C and key component of CSF activity in Xenopus egg extract. Here we show that calcium-activated CaMKII triggers exit from meiosis II by sensitizing the APC/C inhibitor XErp1 for polo-like kinase 1 (Plx1)-dependent degradation. Phosphorylation of XErp1 by CaMKII leads to the recruitment of Plx1 that in turn triggers the destruction of XErp1 by phosphorylating a site known to serve as a phosphorylation-dependent degradation signal. These results provide a molecular explanation for how the fertilization-induced calcium increase triggers exit from meiosis II.     

Eine neue gegen Bilharziose und Amoebiase wirksame Verbindung

Summary 5-[nitro-thiazolyl-(2)]-2-oxo-tetrahydroimidazole was found to possess schistosomicidal and amoebicidal properties. In mice this substance exhibited a curative effect in experimental infections withS. mansoni andS. japonicum. Preliminary clinical trials indicated that the compound is effective and well tolerated in the treatment of vesical bilharziasis.     

Accelerated and prolongated multiplication of antibody-forming spleen cells byBordetella pertussis in mice immunized with sheep red blood cells

Zusammenfassung Der Wirkungsmechanismus immunologischer Adjuvantien ist nicht bekannt. Mittels Anwendung der Jerneschen Technik wurde daher die Frage untersucht, ob Pertussisorganismen ihre adjuvante Wirksamkeit über eine Vermehrung immunologisch kompetenter Zellen entfalten. Es konnte gezeigt werden, dass die simultane Injektion vonB. pertussis und Schaferythrocyten im Vorgleich zur alleinigen Injektion von Schaferythrocyten bei NMRI-Mäusen zu einer beschleunigten, gesteigerten und verlängerten Bildung anti-körperbildender Milzzellen führt.

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This work was supported by research grant No. Fi 115/1 of the Deutsche Forschungsgemeinschaft.     

Formation of anaphylatoxin in human serum

Zusammenfassung Es ist möglich, auch in menschlichem Serum eine Anaphylatoxinbildung (AT) durch Kontaktaktivierung oder Kobragift zu induzieren. Wegen der geringen Mengen, die entstehen, muss das wirksame Prinzip vor dem biologischen Nachweis angereichert werden. Menschliches AT verhält sich in allen untersuchten Eigenschaften wie AT aus anderen Plasmaarten. Es unterscheidet sich von dem darmkontrahierenden Spaltprodukt aus der menschlichen Komplementkomponente C3, das mithin nicht als AT angesprochen werden kann.     

Über die trypanocide Wirksamkeit von Terephthalaniliden

Summary Compounds of the terephthalanilide series show, besides their antileukemic and bacteriostatic properties, considerable activity againstTrypanosoma brucei andT. congolense.      

Effect of ethanol intake on phenytoin metabolism in volunteers.

Ingestion of ethanol, 1 g/kg, did not influence the phenytoin half-life in 5 volunteers after single i.v. administration of 3 mg/kg phenytoin. The control phenytoin half-life was 12.4 h (SD +/- 4.4); with ethanol ingestion it was 12.3 h (SD +/- 5.2).