Studies on the metabolic fate of the14C-labeled methyl group of a methylhydrazine derivative in P815 mouse leukemia

Zusammenfassung Neben der bereits beschriebenen teilweisen Oxydation der endständigen N-Methylgruppe von 1-Methyl-¹⁴C-2-p-(isopropylcarbamoyl)benzylhydrazin-Hydrochlorid (MBH) (NSC 77213) in vivo⁵ lassen die hier aufgeführten Resultate auch auf eine Transmethylierung dieser Methylgruppe schliessen.     

Biophysikalische Studien mit synthetischem Lecithin als Weg zu neuartigen Chemotherapeutika

Summary Based on the behaviour of lecithin in a biophysical cell model, novel compounds have been developed which are regarded as phosphatide blockers in the membrane of the living cell. They inhibit neoplasms in animal experiments to a high degree, and are therefore potential chemotherapeutic agents of great interest.     

The t complex-encoded GTPase-activating protein Tagap1 acts as a transmission ratio distorter in mice

Transmission ratio distortion in the mouse is caused by several t-complex distorters (Tcds) acting in trans on the t-complex responder (Tcr). Tcds additively affect the flagellar movement of all spermatozoa derived from t/+ males; sperm carrying Tcr are rescued, resulting in an advantage for t sperm in fertilization. Here we show that Tagap1, a GTPase-activating protein, can act as a distorter. Tagap1 maps to the Tcd1 interval and has four t loci, which encode altered proteins including a C-terminally truncated form. Overexpression of wild-type Tagap1 in sperm cells phenocopied Tcd function, whereas a loss-of-function Tagap1 allele reduced the transmission rate of the t6 haplotype. The combined data strongly suggest that the t loci of Tagap1 produce Tcd1a. Our results unravel the molecular nature of a Tcd and demonstrate the importance of small G proteins in transmission ratio distortion in the mouse.     

Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways

Cystic renal diseases are caused by mutations of proteins that share a unique subcellular localization: the primary cilium of tubular epithelial cells. Mutations of the ciliary protein inversin cause nephronophthisis type II, an autosomal recessive cystic kidney disease characterized by extensive renal cysts, situs inversus and renal failure. Here we report that inversin acts as a molecular switch between different Wnt signaling cascades. Inversin inhibits the canonical Wnt pathway by targeting cytoplasmic dishevelled (Dsh or Dvl1) for degradation; concomitantly, it is required for convergent extension movements in gastrulating Xenopus laevis embryos and elongation of animal cap explants, both regulated by noncanonical Wnt signaling. In zebrafish, the structurally related switch molecule diversin ameliorates renal cysts caused by the depletion of inversin, implying that an inhibition of canonical Wnt signaling is required for normal renal development. Fluid flow increases inversin levels in ciliated tubular epithelial cells and seems to regulate this crucial switch between Wnt signaling pathways during renal development.     

Testing agile requirements models

This paper discusses a model-based approach to validate software requirements in agile development processes by simulation and in particular automated testing. The use of models as central development artifact needs to be added to the portfolio of software engineering techniques, to further increase efficiency and flexibility of the development beginning already early in the requirements definition phase. Testing requirements are some of the most important techniques to give feedback and to increase the quality of the result. Therefore testing of artifacts should be introduced as early as possible, even in the requirements definition phase.     

Metabolic gene-deletion strains of Escherichia coli evolve to computationally predicted growth phenotypes

Genome-scale metabolic models have a promising ability to describe cellular phenotypes accurately. Here we show that strains of Escherichia coli carrying a deletion of a single metabolic gene increase their growth rates (by 87% on average) during adaptive evolution and that the endpoint growth rates can be predicted computationally in 39 of 50 (78%) strains tested. These results show that computational models can be used to predict the eventual effects of genetic modifications.     

Monitoring of organochlorine pesticides in the urban air of Dalian,China with semipermeable membrane devices

The concentrations of 28 organochlorine pesti- cides （OCPs） in the urban air of Dalian, China were measured using semipermeable membrane devices （SPMDs） for the first time. Alpha-hexachlorocyclohexane （α-HCH）, β-HCH, pentachlorobenzene （PentCB）, hexachlorobenzene （HexCB）, 4,4＇-dichlorodiphenyltrichloroethane （4,4＇-DDT）, 4,4＇- dichlorodiphenyldichloroethene, endosulfan-I and endosul- fan-Ⅱ were the predominant OCPs in the urban air of Dalian. The concentration of OCPs sequestrated by SPMDs （CSPMD） ranged from undetected to 56,772 pg SPMD-1 and had a linear correlation with the reciprocal of the average ambient atmospheric temperature （1/T）. The CSPMD of PentCB and HexCB had negative correlations with T, whereas the other detected OCPs had a positive correlation. The source of HCHs, DDTs, HexCB, PentCB, chlordane, and endosulfan in the air were also evaluated. The OCPs in the urban air of Dalian could be attributed to the seasonal usage of pesticides,combustion, volatilization of aged OCPs from soil, water, plants, and long-range atmospheric transport.     

Comparative genome sequencing of Escherichia coli allows observation of bacterial evolution on a laboratory timescale

We applied whole-genome resequencing of Escherichia coli to monitor the acquisition and fixation of mutations that conveyed a selective growth advantage during adaptation to a glycerol-based growth medium. We identified 13 different de novo mutations in five different E. coli strains and monitored their fixation over a 44-d period of adaptation. We obtained proof that the observed spontaneous mutations were responsible for improved fitness by creating single, double and triple site-directed mutants that had growth rates matching those of the evolved strains. The success of this new genome-scale approach indicates that real-time evolution studies will now be practical in a wide variety of contexts.