Biomedical applications of degradable polyphosphazenes

This article describes the synthesis of biodegradable polyphosphazenes. The rate of degradation can be varied in a controllable manner by the introduction of hydrolysis-sensitive amino acid ester side groups or by blending of polymers. Biodegradable polyphosphazenes can be used for the preparation of drug-containing implants and this is illustrated for devices containing the cytostatic agent mitomycin C. This article reviews data about the degradation characteristics of poly[(amino acid ester)phosphazene] derivatives that have been discussed previously. Some new data about MMC-containing poly[(organo)phosphazene] devices are discussed as well. (c) 1996 John Wiley & Sons, Inc.     

Conditions for Global Dynamic Stability of a Class of Resource-Bounded Model Ecosystems

This paper studies a class of dynamical systems that model multi-species ecosystems. These systems are ‘resource bounded’ in the sense that species compete to utilize an underlying limiting resource or substrate. This boundedness means that the relevant state space can be reduced to a simplex, with coordinates representing the proportions of substrate utilized by the various species. If the vector field is inward pointing on the boundary of the simplex, the state space is forward invariant under the system flow, a requirement that can be interpreted as the presence of non-zero exogenous recruitment. We consider conditions under which these model systems have a unique interior equilibrium that is globally asymptotically stable. The systems we consider generalize classical multi-species Lotka–Volterra systems, the behaviour of which is characterized by properties of the community (or interaction) matrix. However, the more general systems considered here are not characterized by a single matrix, but rather a family of matrices. We develop a set of ‘explicit conditions’ on the basis of a notion of ‘uniform diagonal dominance’ for such a family of matrices, that allows us to extract a set of sufficient conditions for global asymptotic stability based on properties of a single, derived matrix. Examples of these explicit conditions are discussed.     

In vitro acylation of the ϵ-amino group of l-lysine in calf thymus histones by the carcinogen, β-propiolactone

We had previously reported that the carcinogen, β-propiolactone (BPL) reacted in vitro with histones in whole mouse skin chromatin and that among the histone classes BPL was preferentially bound to the lysine-rich histones H1 and H1°. In order to determine if in vitro reaction of BPL with calf thymus histones resulted in binding of BPL to l-lysine, we synthesized the model compounds ?-N-(3-hydroxypropionyl)lysine (HPL) and ?-N-(2-carboxyethyl)lysine (CEL) from BPL and l-lysine. The α-amino group of l-lysine was protected from reaction with BPL by the formation of a copper chelate.Structures were assigned on the basis of infrared spectra, pKa values and chemical analyses. BPL was reacted in vitro with calf thymus histones and the BPL-reacted calf thymus histones and control calf thymus histones were digested with trypsin followed by pronase. The respective digests were each chromatographed on a column of AA-15 cation-exchange resin. The elution profiles of the two digests were very similar except for the appearance of a new ninhydrin-positive peak (NNPP) in the eluate of the trypsin-pronase digest of BPL-reacted calf thymus histones. When compounds HPL and CEL were added to the trypsin-pronase digest of control calf thymus histones and the mixture chromatographed on AA-15, both compounds were resolved from the other peptide (or amino acid) peaks. HPL was eluted in the same fractions as NNPP, HPL and NNPP exhibited identical R_F values on silica gel TLC with acidic, alkaline and neutral solvents. CEL was not identified as a product of the reaction between BPL and calf thymus histones.     

Expression of Yeast NDI1 Rescues a Drosophila Complex I Assembly Defect

Defects in mitochondrial electron transport chain (ETC) function have been implicated in a number of neurodegenerative disorders, cancer, and aging. Mitochondrial complex I (NADH dehydrogenase) is the largest and most complicated enzyme of the ETC with 45 subunits originating from two separate genomes. The biogenesis of complex I is an intricate process that requires multiple steps, subassemblies, and assembly factors. Here, we report the generation and characterization of a Drosophila model of complex I assembly factor deficiency. We show that CG7598 (dCIA30), the Drosophila homolog of human complex I assembly factor Ndufaf1, is necessary for proper complex I assembly. Reduced expression of dCIA30 results in the loss of the complex I holoenzyme band in blue-native polyacrylamide gel electrophoresis and loss of NADH:ubiquinone oxidoreductase activity in isolated mitochondria. The complex I assembly defect, caused by mutation or RNAi of dCIA30, has repercussions both during development and adulthood in Drosophila, including developmental arrest at the pupal stage and reduced stress resistance during adulthood. Expression of the single-subunit yeast alternative NADH dehydrogenase, Ndi1, can partially or wholly rescue phenotypes associated with the complex I assembly defect. Our work shows that CG7598/dCIA30 is a functional homolog of Ndufaf1 and adds to the accumulating evidence that transgenic NDI1 expression is a viable therapy for disorders arising from complex I deficiency.     

Prey Capture Ecology of the Cubozoan Carukia barnesi

Adult Carukia barnesi medusae feed predominantly on larval fish; however, their mode of prey capture seems more complex than previously described. Our findings revealed that during light conditions, this species extends its tentacles and ‘twitches’ them frequently. This highlights the lure-like nematocyst clusters in the water column, which actively attract larval fish that are consequently stung and consumed. This fishing behavior was not observed during dark conditions, presumably to reduce energy expenditure when they are not luring visually oriented prey. We found that larger medusae have longer tentacles; however, the spacing between the nematocyst clusters is not dependent on size, suggesting that the spacing of the nematocyst clusters is important for prey capture. Additionally, larger specimens twitch their tentacles more frequently than small specimens, which correlate with their recent ontogenetic prey shift from plankton to larval fish. These results indicate that adult medusae of C. barnesi are not opportunistically grazing in the water column, but instead utilize sophisticated prey capture techniques to specifically target larval fish.     

Colcemid-resistant mutants of fission yeast have an altered cell cycle

Cell-cycle progression is altered in some colcemid-resistant mutants of fission yeast. The duration of particular stages of the cell cycle is different but total doubling time is unchanged from that of wild type. Cell-plate formation is prolonged relative to wild type but concomitant DNA synthesis is not affected. Separation of daughter cells is inhibited in some strains, giving rise to unusual cell morphologies. Control of cell division is altered in two ways: Critical size for division is increased. The probability of division a function of size is decreased.     

Respiration of thermogenic inflorescences of Philodendron melinonii: natural pattern and responses to experimental temperatures

The patterns of temperature and respiratory changes in the protogynousinflorescences of Philodendron melinonii (Araceae) were studiedin the field in French Guiana. These are the first respiratorymeasurements from a member of the large subgenus Philodendron,a group previously thought to lack thermoregulatory inflorescences,in contrast to thermoregulatory Philodendron species of thesubgenus Meconostigma. Heating by the male and sterile maleflorets was strong on the first evening of anthesis when beetlesare attracted and the female florets are receptive. Heat productionof the inflorescence peaked at 0.9 W and spadix temperaturereached 39.5 °C, a level somewhat independent of ambienttemperature. Thermogenesis continued throughout the night andthe next day, but at a lower level, and floral temperaturesfell. On the second evening, when pollen was shed, there wasa small elevation in respiration and spadix temperature. Responsesof cut spadix sections to experimental step changes in ambienttemperature resulted in a prompt response in floral temperatureand respiration rate in the direction of the change and thena much slower regulatory adjustment in the opposite direction.These responses are consistent with an immediate van 't Hoffeffect, followed by up- or down-regulation of thermogenesis.However, the responses required several hours. It is concludedthat the male floret tissues possess the same thermoregulatorymechanism of more precise thermoregulatory species, but a combinationof small spadix size (that favours heat loss), moderate thermogeniccapacity (that limits heating rate), and slow reaction time(that causes long lags between temperature change and the regulatoryresponse) result in poor thermoregulatory performance duringthe second day. Key words: Arum lily, heat production, inflorescence, Philodendron, protogynous, regulation, respiration, thermogenesis, van 't Hoff effect Received 29 December 2007; Revised 23 January 2008 Accepted 24 January 2008     

The biogeography of the Anura of sub-equatorial Africa and the prioritisation of areas for their conservation

There is an increasing need for protected areas to conserve biodiversity efficiently. The Anura of sub-equatorial Africa have received little attention, but we quantitatively analyse a database containing presence-only data for anurans of sub-equatorial Africa to determine patterns of distribution and species richness, and discuss the roles of present and past environmental conditions in shaping these patterns. We consider the distribution of areas rich in endemic, range-restricted and Red Data Book (RDB) species to identify areas of significance to conservation. The Eastern Highlands of Zimbabwe and adjacent area in Mozambique, southeastern Malawi and the northern coast of KwaZulu/Natal are particularly species rich, whereas the southwestern Cape of South Africa and northwestern Zambia exhibit high degrees of endemism. Four major biogeographical sub-regions are identified, which can be further subdivided into provinces. All statistically significant, current environmental factors together account for 52.6% of species richness. Annual maximum rainfall, soil type variation, minimum temperature and range of elevation were all positively correlated with species richness. Thus, both habitat influences and history appear to have influenced patterns of anuran richness in the region. Generally, areas of high species richness coincide with those high in range-restricted, endemic and RDB species. In South Africa, the northeastern coast and southwestern Cape are hypothesised to have been both refugia and centres of speciation. Results suggest that the current reserve system in sub-equatorial Africa is inadequate for the conservation of the full complement of anuran species in the region.