The effects of cyclophosphamide and nor-nitrogen mustard administration to one-day-old mice

Zusammenfassung Störung der normalen Entwicklung und des Wachstums ein Tag alter Mäuse wurde durch Injektion von Cyclophosphamid verursacht. Verabreichung von Nor-Chlormethin zeigte keine derartigen Effekte und es wird vermutet, dass diese Unterschiede durch die pharmakokinetischen Eigenschaften dieser Stoffe verursacht sein könnten.

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This work was supported by GRS Grant No. 71-0955 awarded by The College of Human Medicine, Michigan State University.     

Regions of variant histone His2AvD required for Drosophila development.

One way in which a distinct chromosomal domain could be established to carry out a specialized function is by the localized incorporation of specific histone variants into nucleosomes. H2AZ, one such variant of the histone protein H2A, is required for the survival of Drosophila melanogaster, Tetrahymena thermophila and mice (R. Faast et al., in preparation). To search for the unique features of Drosophila H2AZ (His2AvD, also referred to as H2AvD) that are required for its essential function, we have performed amino-acid swap experiments in which residues unique to Drosophila His2AvD were replaced with equivalently positioned Drosophila H2A.1 residues. Mutated His2AvD genes encoding modified versions of this histone were transformed into Drosophila and tested for their ability to rescue null-mutant lethality. We show that the unique feature of His2AvD does not reside in its histone fold but in its carboxy-terminal domain. This C-terminal region maps to a short alpha-helix in H2A that is buried deep inside the nucleosome core.     

Exome sequencing of extreme phenotypes identifies DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic fibrosis

Exome sequencing has become a powerful and effective strategy for the discovery of genes underlying Mendelian disorders. However, use of exome sequencing to identify variants associated with complex traits has been more challenging, partly because the sample sizes needed for adequate power may be very large. One strategy to increase efficiency is to sequence individuals who are at both ends of a phenotype distribution (those with extreme phenotypes). Because the frequency of alleles that contribute to the trait are enriched in one or both phenotype extremes, a modest sample size can potentially be used to identify novel candidate genes and/or alleles. As part of the National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP), we used an extreme phenotype study design to discover that variants in DCTN4, encoding a dynactin protein, are associated with time to first P. aeruginosa airway infection, chronic P. aeruginosa infection and mucoid P. aeruginosa in individuals with cystic fibrosis.     

Acquired protein appetite in rats: Dependence on a protein-specific need state

Summary Rats are shown to acquire a preference for protein-predictive olfactory cues which depends on a state of mild deficit in protein intake—i.e. a learned protein-specific appetite.This work was supported by a Medical Research Council Studentship awarded to Leigh Gibson.     

GTPase activity of dynamin and resulting conformation change are essential for endocytosis

Dynamin is a large GTPase with a relative molecular mass of 96,000 (Mr 96K) that is involved in clathrin-mediated endocytosis and other vesicular trafficking processes. Although its function is apparently essential for scission of newly formed vesicles from the plasma membrane, the nature of dynamin's role in the scission process is still unclear. It has been proposed that dynamin is a regulator (similar to classical G proteins) of downstream effectors. Here we report the analysis of several point mutants of dynamin's GTPase effector (GED) and GTPase domains. We show that oligomerization and GTP binding alone, by dynamin, are not sufficient for endocytosis in vivo. Rather, efficient GTP hydrolysis and an associated conformational change are also required. These data argue that dynamin has a mechanochemical function in vesicle scission.     

THE SUDBURY STRUCTURE : AN INTRODUCTION

The capital of the world’s nickel,Sudbury in north Ontario,is named for the SudburyStructure.The Sudbury Structure and its associated Cu-Ni sulphide deposits is a signifi-cant geological record on the earth.Detailed study of the Sudbury Structure has suggest-ed that the Sudbury Structure is a violent structure,widely regarded as meteoritic shock-ing structure.The footwall rock of the structure is Precambrian metamorphic rockswhich has subjected shock metamorphism and formed Sudbury Breccia partly.The Sud-bury Igneous Complex(SIC)is a controversial igneous rocks,compositionally from quartznorite to granophyre and quartz diorite—offset dikes,for its special composition andgeological occurrence.The hang-wall rock,Whitewater Group,is more complex and in-terpreted as an ignimbrite or the fallback breccia from the impact of a meteorite.Coinci-dentally,the Sudbury Structure is located on the east-tending Elliot Lake—Englehartpositive gravity anomaly and at the"Junction"of three structure provinces,and also