Correlation of anthothecol and hirtin

Summary Hirtin (3) and anthothecol (2) have been correlated by conversion of each to the derivative (10).     

MDC1 is a mediator of the mammalian DNA damage checkpoint

To counteract the continuous exposure of cells to agents that damage DNA, cells have evolved complex regulatory networks called checkpoints to sense DNA damage and coordinate DNA replication, cell-cycle arrest and DNA repair. It has recently been shown that the histone H2A variant H2AX specifically controls the recruitment of DNA repair proteins to the sites of DNA damage. Here we identify a novel BRCA1 carboxy-terminal (BRCT) and forkhead-associated (FHA) domain-containing protein, MDC1 (mediator of DNA damage checkpoint protein 1), which works with H2AX to promote recruitment of repair proteins to the sites of DNA breaks and which, in addition, controls damage-induced cell-cycle arrest checkpoints. MDC1 forms foci that co-localize extensively with gamma-H2AX foci within minutes after exposure to ionizing radiation. H2AX is required for MDC1 foci formation, and MDC1 forms complexes with phosphorylated H2AX. Furthermore, this interaction is phosphorylation dependent as peptides containing the phosphorylated site on H2AX bind MDC1 in a phosphorylation-dependent manner. We have shown by using small interfering RNA (siRNA) that cells lacking MDC1 are sensitive to ionizing radiation, and that MDC1 controls the formation of damage-induced 53BP1, BRCA1 and MRN foci, in part by promoting efficient H2AX phosphorylation. In addition, cells lacking MDC1 also fail to activate the intra-S phase and G2/M phase cell-cycle checkpoints properly after exposure to ionizing radiation, which was associated with an inability to regulate Chk1 properly. These results highlight a crucial role for MDC1 in mediating transduction of the DNA damage signal.     

Evidence that the insulin secretagogue, beta-cell-tropin, is ACTH22-39

The pituitary neurointermediate lobe of genetically obese (ob/ob) mice contains a hormone which stimulates insulin release and which cross-reacts with a -COOH-terminal ACTH antiserum, suggesting that it is related to corticotropin-like intermediate lobe peptide (CLIP), the 18-39 fragment of ACTH. The hormone, which we have called beta-cell-tropin, has been shown to be present in the plasma of the ob/ob mouse and to potentiate glucose induced insulin secretion. We have now shown that ACTH22-39 prepared by tryptic digestion of human synthetic CLIP behaves similarly on Biogel chromatography and on reverse-phase HPLC to the naturally occurring beta-cell-tropin. Furthermore, beta-cell-tropin and ACTH22-39 have indistinguishable antigenic and insulin releasing properties.     

Tissue distribution and nucleic acid binding of chlorambuci-3H in tumor-bearing rats

Summary In tumour and normal rat tissues prolonged alkylation of DNA and RNA by chlorambucil-³H occurs over periods of 24 h. It is suggested that this may indicate the slow release of an alkylating moiety from an intracellular drugmacromolecule complex.     

Haemopoietic colony stimulating factors promote cell survival by suppressing apoptosis.

The survival, differentiation, proliferation and development of haemopoietic precursor cells and the functional activity of mature blood cells are all influenced by colony stimulating factors (CSFs). As haemopoietic cells rapidly die in the absence of appropriate CSF, the promotion of cell survival mediated by CSFs, or growth factors, is fundamental to all the other effects exerted by these factors. This enhancement of cell survival is distinct from the stimulation of proliferation. Here we show that the death of haemopoietic precursor cells on withdrawal of the relevant CSF. is due to active cell death, or apoptosis, indicating that CSFs promote cell survival by suppression of the process of apoptosis. The existence of a positive control mechanism regulating precursor cell survival has important implications both for the regulation of normal haemopoiesis and for tumorigenesis.     

The effect of endotoxin on membrane fatty acid composition in BCG-sensitized mice

Summary The effects of endotoxin on mouse liver phospholipid fatty acid composition have been investigated. Administration of endotoxin fromSalmonella abortus equi led to a decrease in the polyunsaturated fatty acid content of livers from mice sensitized with Bacille Calmette Guérin (GCG). The content of arachidonic acid fell significantly in both the phosphatidylcholine and phosphatidylinositol fractions whereas in the phosphatidylethanolamine fraction the linoleic acid content was significantly reduced. The polyunsaturated fatty acids were replaced by increased amounts of oleic acid and palmitic acid, leading to a reduction in the polyunsaturated to saturated fatty acid ratio.     

Consequences of sulphate-reducing bacterial growth in a lab-simulated waste disposal regime

Summary Experiments are described which investigate corrosion of forged 0.2% carbon steel in the presence of sulphate reducing bacteria (SRB). Cultures of a thermophilic bacteriumDesulfotomaculum nigrificans were mixed with bentonite and synthetic groundwater to simulate a bacteria-contamined backfill, and placed in contact with carbon steel disc specimens in perspex cells at 50°C under anaerobic conditions. The rates of corrosion were monitored by electrochemical techniques, together with changes in near field redox potential. After 340 days the nature and extent of any corrosion was measured and the SRB content of the bentonite determined. Recovery of relatively large numbers of bacteria after about one year incubation in an alkaline (pH 9.5) medium confirmed the pH tolerance of the strain. Enhanced corrosion (three times the rate of the control) occurred in at least two of the five cells that contained SRB despite the nutritionally poor environment which existed in the bentonite gel.     

Smooth muscle in the hepatic artery, portal vein and hepatic vein within the liver of the raccoon and guinea pig

The amount and arrangement of smooth muscle in the intrahepatic vessels suggests that the guinea pig would be a good animal model for studying mechanisms controlling intrahepatic portal vein blood flow, while the raccoon would be good for studying hepatic vein mechanisms of control.