The roles of WRN and BLM RecQ helicases in the Alternative Lengthening of Telomeres

Approximately 10% of all cancers, but a higher proportion of sarcomas, use the recombination-based alternative lengthening of telomeres (ALT) to maintain telomeres. Two RecQ helicase genes, BLM and WRN, play important roles in homologous recombination repair and they have been implicated in telomeric recombination activity, but their precise roles in ALT are unclear. Using analysis of sequence variation present in human telomeres, we found that a WRN– ALT+ cell line lacks the class of complex telomere mutations attributed to inter-telomeric recombination in other ALT+ cell lines. This suggests that WRN facilitates inter-telomeric recombination when there are sequence differences between the donor and recipient molecules or that sister-telomere interactions are suppressed in the presence of WRN and this promotes inter-telomeric recombination. Depleting BLM in the WRN– ALT+ cell line increased the mutation frequency at telomeres and at the MS32 minisatellite, which is a marker of ALT. The absence of complex telomere mutations persisted in BLM-depleted clones, and there was a clear increase in sequence homogenization across the telomere and MS32 repeat arrays. These data indicate that BLM suppresses unequal sister chromatid interactions that result in excessive homogenization at MS32 and at telomeres in ALT+ cells.     

THE INSECTICIDES—Their Hazard in Industry and in the Home Part II—Clinical Aspect

Within the past decade the chemist has evolved a new group of insecticides having a greater range of toxicity to insects—and to man. Since their use is ubiquitous, it is imperative that information be widely disseminated regarding proper cautionary measures as well as the early signs and symptoms of toxicity.     

PRINCIPLES OF DIAGNOSING OCCUPATIONAL DISEASES—Special Considerations to Avoid “Creating” an Entity

The traditional diagnostic procedure adhered to in general medicine is too frequently neglected when a physician is confronted with a possible occupational disease. Also, the proper diagnosis in occupational medicine requires additional effort along lines of investigation not necessary in general medicine. Failure to conform to the basic steps as outlined in this paper will distort known entities or “create” false ones.     

Purification and properties of a germination-specific cortex-lytic enzyme from spores of Bacillus megaterium KM.

Two peptidoglycan-lytic enzyme activities were isolated from spores of Bacillus megaterium KM. Surface-bound lytic enzyme was extracted from dormant spores and hydrolysed a variety of peptidoglycan substrates including isolated spore cortex, but did not cause refractility changes in permeabilized spores. Germination-specific lytic enzyme activity appeared early in germination and had minimal activity on isolated peptidoglycan substrates, but caused refractility changes in permeabilized spores of several Bacillus isolated peptidoglycan substrates, but caused refractility changes in permeabilized spores of several Bacillus species. The germination-specific lytic enzyme was shown to be a heat-sensitive 29 kDa protein with maximal activity at pH 6.5. It catalysed post-commitment muramic acid delta-lactam synthesis and displayed an inhibitor profile similar to that for post-commitment A600 loss. The relationship of the germination-specific enzyme to a recently proposed model of spore germination is discussed.     

Differential control of proto-oncogene c-myc and c-fos expression in lymphocytes and fibroblasts.

In lymphocytes stimulated with the mitogen phytohaemagglutinin, an inhibitor of the enzyme ADP-ribosyltransferase (ADPRT) completely blocks the proliferative response and the increase in expression of the proto-oncogene c-myc without affecting c-fos significantly. Conversely, in fibroblasts the serum-induced growth is not affected by the ADPRT inhibitor, and both oncogenes are dramatically super-induced. Hence there are differences between lymphocyte and fibroblast early responses to mitogenic stimulation and also between regulation of c-fos and c-myc gene expression.     

The influence of ration size and feeding frequency on ammonia excretion by juvenile Atlantic cod, Gadus morhua L.

Small groups of juvenile Atlantic cod, Gadus morhua L., were kept at 14°C in through-flow tanks and were fed known quantities of a compounded diet of natural food. The cod were fed single and multiple meals with ration size in the range 0.5 to 4.1% of total wet fish body weight. Ammonia production in each feeding experiment was monitored continuously.
For single-meal experiments, significant relationships were derived between ration size and (a) total ammonia excreted, (b) total exogenous ammonia excreted above endogenous excretion levels, (c) duration of the elevated phase of ammonia excretion, (d) maximum rate of ammonia excretion, and (e) time delay after feeding to reach maximum rate of ammonia excretion. Relationships between nitrogen loss as ammonia and nitrogen intake were examined and estimates of endogenous excretion rate and maintenance ration made.
Repetitive feeding resulted in cyclical variation in ammonia excretion. At the lowest ration size, ammonia excretion rates had nearly returned to the pre-feeding level within 24 h. At higher feeding levels, the effect of each successive meal tended to be cumulative, resulting in increasingly higher ammonia excretion rates which only stabilized towards the end of the experiments.     

Phosphoinositide hydrolysis in mitogen-stimulated human peripheral-blood T lymphocytes.

Both phytohaemagglutinin and antibodies to the CD3 molecule induced proliferation and phosphoinositide hydrolysis in human peripheral-blood T lymphocytes, but the magnitude of the inositol phosphate response was small and the rate of accumulation slow [significant increases in Ins(1,4,5)P3 were observed only after 10 min]. Hence this response differs from the well-characterized Ins(1,4,5)P3 responses of many other systems. This slow response, its abrogation in Ca2+-depleted medium, the slow and maintained increase in Ca2+ as measured by Quin-2, and the ability of the Ca2+ ionophore A23187 to stimulate Ins(1,4,5)P3 accumulation all suggest that the increase in Ins(1,4,5)P3 occurs, at least in part, as a result of receptor-mediated Ca2+ influx in mitogen-stimulated T lymphocytes.