The structural relationship of phorbol and cortisol: A possible mechanism for the tumor promoting activity of phorbol

Summary The crucial functional groups of phorbol-12-myristate-13-acetate (PMA) are superimposable with those of the glucocorticoid cortisol in a unique manner which suggests a mechanism for PMA activity, i.e. the alkylation of a cortisol receptor.     

The suppression of mouse spontaneous locomotor activity by the ingestion of deuterium oxide.

The spontaneous locomotor activity of the laboratory mouse is significantly depressed by the ingestion of deuterium oxide. The response, which is reversible, is a retilinear one with up to 70% reduction in activity with the administration of 25% heavy water.     

Effect of heat treatment on the ATPase activity of various sarcoplasmic reticulum preparations.

Ca2+-stimulated ATPase activity of sarcoplasmic reticulum (SR) preparations is activated after a short period of preincubation at temperatures between 40 and 45 degrees C, but for temperatures higher than 48 degrees C pronounced denaturation is observed. Heat denaturation is decreased if Mg2+ or K+ are present during heat treatment.     

Organization of myosin molecules in the muscle thick filament

Summary Tryptic treatment of muscle thick filaments reveals the underlying backbones of aggregatedl-meromyosin as a coli of 3 secondary filaments (helical repeat 130 nm) each in turn a coli of a 3 finer ones.     

Blood plasma investigations by resonance raman spectroscopy: Detection of carotenoid pigments

Summary Using Raman spectroscopy, we demonstrate that low levels of -carotene, lycopene, and xanthophyll give rise to resonance enhanced bands in blood plasma. These results explain the significance of previously unidentified spectral maxima which have been related to the state of health of the blood donor.     

Two classes of metabolites fromTheonella swinhoei are localized in distinct populations of bacterial symbionts

The marine spongeTheonella swinhoei (lithistid Family Theonellidae, Order Astrophorida) has yielded many important, bioactive natural products, most of which share structural features with bacterial natural products. The presence of microbial symbionts inT. swinhoei has been reported, and it was originally suggested that the cytotoxic macrolide swinholide A and many of the bioactive cyclic peptides fromT. swinhoei were all produced by symbiotic cyanobacteria. By transmission electron microscopy, we found four distinct cell populations to be consistently present inT. swinhoei: eukaryotic sponge cells, unicellular heterotrophic bacteria, unicellular cyanobacteria and filamentous heterotrophic bacteria. Purification and chemical analyses of each cell type showed the macrolide swinholide A to be limited to the mixed population of unicellular heterotrophic bacteria, and an anti-fungal cyclic peptide occurred only in the filamentous heterotrophic bacteria. Contrary to prior speculation, no major metabolites were located in the cyanobacteria or sponge cells.     

Minimum information about a microarray experiment (MIAME)-toward standards for microarray data.

Microarray analysis has become a widely used tool for the generation of gene expression data on a genomic scale. Although many significant results have been derived from microarray studies, one limitation has been the lack of standards for presenting and exchanging such data. Here we present a proposal, the Minimum Information About a Microarray Experiment (MIAME), that describes the minimum information required to ensure that microarray data can be easily interpreted and that results derived from its analysis can be independently verified. The ultimate goal of this work is to establish a standard for recording and reporting microarray-based gene expression data, which will in turn facilitate the establishment of databases and public repositories and enable the development of data analysis tools. With respect to MIAME, we concentrate on defining the content and structure of the necessary information rather than the technical format for capturing it.     

Cadmium is a mutagen that acts by inhibiting mismatch repair

Most errors that arise during DNA replication can be corrected by DNA polymerase proofreading or by post-replication mismatch repair (MMR). Inactivation of both mutation-avoidance systems results in extremely high mutability that can lead to error catastrophe. High mutability and the likelihood of cancer can be caused by mutations and epigenetic changes that reduce MMR. Hypermutability can also be caused by external factors that directly inhibit MMR. Identifying such factors has important implications for understanding the role of the environment in genome stability. We found that chronic exposure of yeast to environmentally relevant concentrations of cadmium, a known human carcinogen, can result in extreme hypermutability. The mutation specificity along with responses in proofreading-deficient and MMR-deficient mutants indicate that cadmium reduces the capacity for MMR of small misalignments and base-base mismatches. In extracts of human cells, cadmium inhibited at least one step leading to mismatch removal. Together, our data show that a high level of genetic instability can result from environmental impediment of a mutation-avoidance system.     

Complex reorganization and predominant non-homologous repair following chromosomal breakage in karyotypically balanced germline rearrangements and transgenic integration

We defined the genetic landscape of balanced chromosomal rearrangements at nucleotide resolution by sequencing 141 breakpoints from cytogenetically interpreted translocations and inversions. We confirm that the recently described phenomenon of 'chromothripsis' (massive chromosomal shattering and reorganization) is not unique to cancer cells but also occurs in the germline, where it can resolve to a relatively balanced state with frequent inversions. We detected a high incidence of complex rearrangements (19.2%) and substantially less reliance on microhomology (31%) than previously observed in benign copy-number variants (CNVs). We compared these results to experimentally generated DNA breakage-repair by sequencing seven transgenic animals, revealing extensive rearrangement of the transgene and host genome with similar complexity to human germline alterations. Inversion was the most common rearrangement, suggesting that a combined mechanism involving template switching and non-homologous repair mediates the formation of balanced complex rearrangements that are viable, stably replicated and transmitted unaltered to subsequent generations.