Intrinsic disorder in the kinesin superfamily

Kinesin molecular motors perform a myriad of intracellular transport functions. While their mechanochemical mechanisms are well understood and well-conserved throughout the superfamily, the cargo-binding and regulatory mechanisms governing the activity of kinesins are highly diverse and, in general, incompletely characterized. Here we present evidence from bioinformatic predictions indicating that most kinesin superfamily members contain significant regions of intrinsically disordered (ID) residues. ID regions can bind to multiple partners with high specificity and are highly labile to post-translational modification and degradation signals. In kinesins, the predicted ID regions are primarily found in areas outside the motor domains, where primary sequences diverge by family, suggesting that the ID may be a critical structural element for determining the functional specificity of individual kinesins. To support this concept, we present a systematic analysis of the kinesin superfamily, family by family, for predicted ID regions. We combine this analysis with a comprehensive review of kinesin-binding partners and post-translational modifications. We find two key trends across the entire kinesin superfamily. First, ID residues tend to be in the tail regions of kinesins, opposite the superfamily-conserved motor domains. Second, predicted ID regions correlate to regions that are known to bind to cargoes and/or undergo post-translational modifications. We therefore propose that the ID residue is a structural element utilized by the kinesin superfamily in order to impart functional specificity to individual kinesins.     

Apparently monogenic inheritance of anencephaly and spina bifida in a kindred

Summary Anencephaly and/or spina bifida has been observed in 5 of 8 children from 2 related families. The fathers of both families were brothers and had married 2 sisters. By further investigation they could be shown to be third degree cousins to their marriage partners. No malformations were known among further relatives. The family pattern suggests autosomal recessive inheritance of anencephalus and/or spina bifida in this family, although it could not be excluded, that genetically determined intrauterine factors were of importance.

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Zusammenfassung In 2 verwandten Familien einer Sippe hatten 5 von 8 Kindern Anencephalie und/oder Meningocele. Die Väter beider Familien waren Brüder, die Mütter Schwestern. Das Studium der Kirchenbücher ergab, daß die Ehepartner außerdem Vettern und Basen dritten Grades waren. Weder den Eltern noch dem Hausarzt waren bei weiteren Verwandten Fehlbildungen ähnlicher oder anderer Art bekannt. Der Stammbaum macht autosomal-recessiven Erbgang der Schulßstörung des Neuralrohres in dieser Familie sehr wahrscheinlich, es kann jedoch nicht mit voller Sicherheit ausgeschlossen werden, daß erblich bedingte intrauterine Faktoren entscheidend waren.

     

Isolation and identification of 15-beta-hydroxy cyproterone acetate as a new metabolite of cyproterone acetate in dog, monkey and man.

15-beta-hydroxy cyproterone acetate could be identified by thin layer chromatography, mass spectrum, NMR and IR spectrum as a major unconjugated metabolite of cyproterone acetate in plasma and urine of dog, monkey and man. This metabolite has been found to interferein the Mattingly method for the determination of 11-hydroxy-corticosteroids which suggests, that this method is inadequate in controling the adrenal function of subjects treated with cyproterone acetate.     

Establishment of helophytes in the course of fen restoration

Abstract. In two fen areas of northeastern Germany, different techniques of re-introduction to establish reed-bed species in formerly intensively used, species-poor, grasslands, after rewetting, were studied under three hydrological regimes (permanent inundation, temporary inundation, border irrigation) with the aims (1) to establish peat-forming vegetation and (2) to enhance species richness. Establishment was successful for nearly all species investigated under all hydrological variants. There were differences between individuals sown and those which had been planted. Wet, but not inundated soil linked with vegetation gaps create ‘safe sites’ which enable successful germination and seedling establishment. The survival rate for both planted and sown individuals was generally high, with the exception of Cladium mariscus, Eupatorium cannabinum and Phragmites australis Recommendations for restoration management include the establishment of the following successful species: Carex acutiformis, C elata and C paniculata to establish peat-forming vegetation; Iris pseudacorus, Lysimachia vulgaris, Lythrum salicaria to enhance species richness.     

Tamoxifen dosing for Cre-mediated recombination in experimental bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth characterized by blunted post-natal lung development. BPD can be modelled in mice by exposure of newborn mouse pups to elevated oxygen levels. Little is known about the mechanisms of perturbed lung development associated with BPD. The advent of transgenic mice, where genetic rearrangements can be induced in particular cell-types at particular time–points during organogenesis, have great potential to explore the pathogenic mechanisms at play during arrested lung development. Many inducible, conditional transgenic technologies available rely on the application of the estrogen-receptor modulator, tamoxifen. While tamoxifen is well-tolerated and has been widely employed in adult mice, or in healthy developing mice; tamoxifen is not well-tolerated in combination with hyperoxia, in the most widely-used mouse model of BPD. To address this, we set out to establish a safe and effective tamoxifen dosing regimen that can be used in newborn mouse pups subjected to injurious stimuli, such as exposure to elevated levels of environmental oxygen. Our data reveal that a single intraperitoneal dose of tamoxifen of 0.2 mg applied to newborn mouse pups in 10 μl Miglyol vehicle was adequate to successfully drive Cre recombinase-mediated genome rearrangements by the fifth day of life, in a murine model of BPD. The number of recombined cells was comparable to that observed in regular tamoxifen administration protocols. These findings will be useful to investigators where tamoxifen dosing is problematic in the background of injurious stimuli and mouse models of human and veterinary disease.