A cellular model for drug interactions on hematopoiesis: The use of human umbilical cord blood progenitors as a model for the study of drug-related myelosuppression of normal hematopoiesis

A cellular model of hematopoiesis which would be more convenient than bone marrow (BM) progenitors and directly relevant to human pathology is needed in order to investigate xenobiotic toxicity. Human umbilical cord blood (HCB), previously shown to be able to repopulate BM, provides a powerful in vitro model of normal human hematopoiesis. In order to validate the use of normal HCB progenitors as targets for dose-related myelosuppression, we used clonogenic assays and expansion in a liquid culture of progenitor-enriched cell suspensions from HCB. A series of 8 reference molecules, doxorubicin, cytosine-arabinoside, 5-fluorouracil, 3-azido-3-deoxythymidine, acetylsalicyclic acid, sodium valproate and two cephalosporin antibiotics, were tested. In vitro 50% inhibition concentrations (IC₅₀) were compared to those observed or reported with BM progenitors, and to the values of plasma concentrations from treated patients. HCB progenitors as in vitro targets for cytotoxic molecules were easy to access and handle, and their use was sensitive, specific and reproducible. They gave results similar to BM progenitors and allowed a qualitative approach to cellular metabolism and toxicity using morphological, flow cytometric and chromatographic methods.Abbreviations ARA-CC cytosine arabinoside - AS acetylsalicylic acid - AZTT 3-azido-3-deoxythymidine - BFUU burst-forming units - BM bone marrow - CFU colony-forming units - DOXX doxorubicin - FU 5-fluorouracil - glyAA glyAcophorin A - HCB human umbilical cord blood - IU international units - PCMEM human placenta-conditioned medium - VA sodium valproate     

Ultra-fastChara myosin: A test case for the swinging lever arm model for force production by myosin

Recent breakthroughs and technological improvements are rapidly generating evidence supporting the “swinging lever arm model” for force production by myosin. Unlike previous models, this model posits that the globular domain of the myosin motor binds to actin with a constant orientation during force generation. Movement of the neck domain of the motor is hypothesized to occur relative to the globular domain much like a lever arm. This intramolecular conformational change drives the movement of the bound actin. The swinging lever arm model is supported by or consistent with a large number of experimental data obtained with skeletal muscle or slime mold myosins, all of which move actin filaments at rates between 1 and 10 μm/sin vitro. Recently myosin was purified, fromChara internodal cells.In vitro the purifiedChara myosin moves actin filaments at rates one order of magnitude faster than the “fast” skeletal muscle myosin. While this ultra fast movement is not necessarily inconsistent with the swinging lever arm model, one or more specific facets of the motor must be altered in theChara motor in order to accommodate such rapid movement. These characteristics are experimentally testable, thus the ultra fast movement byChara myosin represents a powerful and compelling test of the swinging lever arm model.     

棉铃虫致病菌BT—931菌株的应用研究

１９９２－１９９３年,作者从菏泽、聊城棉田采集的自然罹病死亡棉铃虫幼虫体内,分离到２个较高毒效的Ｂｔ菌株,编号为ＢＴ—９３１和ＢＴ—０２１,经室内毒力测定和田间药效试验表明,防效及保蕾效果接近或超过化学农药,菌药混剂３—５天平均防治效果达８７．０－９１．６％,增效作用显著。经１９９４年大田防治示范表明,利用ＢＴ—９３１菌剂。配合化学农药防治棉铃虫,具有成本低、保护天敌、持效期长、增产效益高等优点。本研究对菌剂的田间应用技术进行了试验示范。     

Strange limits of stability in host-parasitoid systems

The classical Nicholson-Bailey model for a two species host-parasitoid system with discrete generations assumes random distributions of both hosts and parasitoids, randomly searching parasitoids, and random encounters between the individuals of the two species. Although unstable, this model induced many investigations into more complex host-parasitoid systems. Local linearized stability analysis shows that equilibria of host parasitoid systems within the framework of a generalized Nicholson-Bailey model are generally unstable. Stability is only possible if host fertility does not exceede ⁴=54.5982 and if superparasitism is unsuccessful. This special situation has already been discovered by Hassell et al. (1983) in their study of the effects of variable sex ratios on host parasitoid dynamics. We discuss global behaviour of the Hassell-Waage-May model using KAM-theory and illustrate its sensitivity to small perturbations, which can give rise to radically different patterns of the population dynamics of interacting hosts and parasitoids.     

Kinetics of leucrose formation from sucrose by dextransucrase

Leucrose formation from sucrose and fructose by dextransucrase is of practical interest. It has been investigated at different experimental conditions, including the influence of temperature on reaction rate and selectivity. Under appropriate conditions high product yield can be obtained. Furthermore, a model is presented that allows interpretation of the experimental data.     

Analysis of nitrogen saturation potential in Rocky Mountain tundra and forest: implications for aquatic systems

We employed grass and forest versions of the CENTURY model under a range of N deposition values (0.02–1.60 g N m^–2 y^–1) to explore the possibility that high observed lake and stream N was due to terrestrial N saturation of alpine tundra and subalpine forest in Loch Vale Watershed, Rocky Mountain National Park, Colorado. Model results suggest that N is limiting to subalpine forest productivity, but that excess leachate from alpine tundra is sufficient to account for the current observed stream N. Tundra leachate, combined with N leached from exposed rock surfaces, produce high N loads in aquatic ecosystems above treeline in the Colorado Front Range. A combination of terrestrial leaching, large N inputs from snowmelt, high watershed gradients, rapid hydrologic flushing and lake turnover times, and possibly other nutrient limitations of aquatic organisms constrain high elevation lakes and streams from assimilating even small increases in atmospheric N. CENTURY model simulations further suggest that, while increased N deposition will worsen the situation, nitrogen saturation is an ongoing phenomenon.     

Protochlorophyllide forms in non-greening epicotyls of dark-grown pea (Pisum sativum)

Low-temperature fluorescence emission spectra of 6.5-day-old dark-grown epicotyls of pea ( Pisum sativum ) revealed the presence of protochlorophyll(ide). The upper part of the epicotyl contained 30% of the protochlorophyll(ide) content per fresh weight found in pea leaves, whereas the lower part contained 3%. Three discrete spectral forms of protochlorophyll(ide) were clearly distinguished after Gaussian deconvolution of fluorescence excitation and emission spectra. Adding the satellite bands of the Qy_(0-0) transitions (the emission vibrational (Emv) bands with correlated amplitudes, gave the following delineation: Ex439–Em629–Emv684, Ex447–Em636–Emv700 and Ex456–Em650–Emv728. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) followed by immunodetection of whole tissue extracts of the epicotyl indicated the presence of NADPH-protochlorophyllide oxidoreductase (EC 1.3.1.33). Electron micrographs showed prolamellar bodies in at most 11 % of the plastid profiles of the epicotyl cells. These prolamellar bodies were smaller, and many of them showed less regular structure than those of the leaves. Taken together, the results indicate that the protochlorophyll(ide) in epicotyls is arranged in a different way than in leaves.     

Tropical tree species diversity: a test of the Janzen-Connell model

To test the premises and predictions of the Janzen-Connell model (Janzen's spacing mechanism), seeds of the rainforest canopy tree, Brosimum alicastrum, were placed at different distances from the parent tree and their removal observed over 3 weeks. The number and density of naturally occurring seeds at different distances from the parent tree were also estimated. Predation was not greater near the parent tree, except on the very small spatial scale: the proportion of experimental seeds removed was greater 1 m from the trunk than it was 5–25 m from the trunk. Predation was negatively correlated with seed density, not positively as the Janzen-Connell model assumes-presumably due to predator satiation. The density of seeds after predation peaked 5 m from the tree trunk, but this is well within the crown radius of the parent tree. There is a peak in the number of potential recruits at a distance of 10 m from the parent tree, due to the peaked initial distribution of seeds. This peak is caused by the interaction between the seed density curve and the increasing area of an annulus around the parent tree at increasing distances, not by the product of the density curve and the predation curve. However, it is important to realize that it is not the presence of a peak in recruitment away from the parent that is essential to maintaining tropical tree species diversity, but frequency-dependent recruitment induced by poor recruitment near conspecifics. Predator satiation seems to be an important factor in the survival of B. alicastrum seeds, possibly at several spatial scales. The number of seeds produced by the tree is negatively correlated with the loss to predators, and trees that have a fruiting conspecific nearby also suffer lower levels of predation. Seed predation increases as one moves from the forest edge into the interior, creating an edge effect that may have long-term effects on the forest composition and tree species diversity. More studies are needed, for other species, other localities, and larger spatial and temporal scales, on both the Janzen-Connell mechanism and this edge effect.