Impact of PNKP mutations associated with microcephaly, seizures and developmental delay on enzyme activity and DNA strand break repair

Microcephaly with early-onset, intractable seizures and developmental delay (MCSZ) is a hereditary disease caused by mutations in polynucleotide kinase/phosphatase (PNKP), a DNA strand break repair protein with DNA 5'-kinase and DNA 3'-phosphatase activity. To investigate the molecular basis of this disease, we examined the impact of MCSZ mutations on PNKP activity in vitro and in cells. Three of the four mutations currently associated with MCSZ greatly reduce or ablate DNA kinase activity of recombinant PNKP at 30°C (L176F, T424Gfs48X and exon15Δfs4X), but only one of these mutations reduces DNA phosphatase activity under the same conditions (L176F). The fourth mutation (E326K) has little impact on either DNA kinase or DNA phosphatase activity at 30°C, but is less stable than the wild-type enzyme at physiological temperature. Critically, all of the MCSZ mutations identified to date result in ∼10-fold reduced cellular levels of PNKP protein, and reduced rates of chromosomal DNA strand break repair. Together, these data suggest that all four known MCSZ mutations reduce the cellular stability and level of PNKP protein, with three mutations likely ablating cellular DNA 5'-kinase activity and all of the mutations greatly reducing cellular DNA 3'-phosphatase activity

Inhibitory effect of Anabaena sp. on in situ filtering rate of Daphnia

We found that in situ filtering rates of Daphnia spp. measured in a lake containing Anabaena were significantly lower than those measured in a filament-free lake. Even after accounting for the depressing effects of high nannoplankton biomass concentration, filtering rates in the lake with Anabaena were 64% lower than those from the filament-free lake. We also found that filtering rates for Daphnia pulex in laboratory experiments were lower when Anabaena was present in experimental beakers than when Chlorella was present. When Anabaena was removed from Three Mile Lake water, filtering rates compared closely with predicted rates based on nannoplankton concentration and carapace length alone. Our analysis indicates that the presence of Anabaena filaments depresses Daphnia grazing rates in general, and that the filaments themselves are ingested at a lower rate than algae such as Chlorella. </jats:p

Type-3 functional response in limnetic suspension-feeders, as demonstrated by in situ grazing rates

Field-measured grazing rates (ml/animal/d) of cladocerans (mostly daphniids) and diaptomids were assembled from various published studies and plotted as a function of corresponding phytoplankton concentration (μg l-1 f.w.). Filtering rates of both zooplankton groups initially increased with seston concentration until maximal grazing rates were observed at approximately 4 × 102 and 1 × 102 μg l-1 for cladocerans and copepods, respectively; at higher algal concentrations, filtering rates of both declined as a function of food concentration. The shape of these curves are most consistent with Holling's (1966) Type 3 functional response. We found little support for the Type 3 functional response in published laboratory studies of Daphnia; most investigators report either a Type 1 or Type 2 response. The one study in which the Type 3 response was observed involved experiments where animals were acclimated at low food concentrations for 24 h, whereas those studies associated with response Types 1 or 2 had acclimation periods of only 1 to 3 h. We therefore assembled relevant data from the literature to examine the effect of acclimation period on the feeding rates of Daphnia at low food concentrations. In the absence of any acclimation, animals filtered at extremely low rates. After 2 h of acclimation, however, filtering rates increased 4 to 5-fold but declined again with longer durations; after > 70 h of pre-conditioning, filtering rates were almost as low as they had been with no acclimation. We also found little support for the Type 3 functional response in published studies of copepods. The only study associated with a Type 3 response involved a marine copepod that had been subjected to a starvation period of 48 h; however, an analysis of the effects of acclimation period did not yield conclusive evidence that filtering rates of freshwater copepods (Diaptomus and Eudiaptomus) decrease significantly with acclimation duration. The low filtering rates associated with long acclimation periods in laboratory experiments appears to be a direct result of animals becoming emaciated from prolonged exposure to low food concentrations, a situation which renders them incapable of high filtering rates. This may explain the Type 3 functional response for field cladocerans, since zooplankton in food-limiting situations are constantly exposed to low food concentrations, and would therefore have low body carbon and consequently less energy to filter-feed. We cannot, however, use this to explain the Type 3 response for field diaptomids, since copepods in the laboratory did not appear to lose body carbon even after 72 h of feeding at very low food levels, and there was inconclusive evidence that either Diaptomus or Eudiaptomus decrease their filtering rates with acclimation period. Although Incipient Limiting Concentrations (ILC) for Daphnia ranged from 1 to 8.5 × 103 μg 1-1, more than half of these fell between 1 and 3 × 103 μg l-1, bracketing the value of 2.7 × 102 μg l-1 for field cladocerans. There was, however, a great deal of variation in reported maximum ingestion rates (MIR), maximum filtering rates (MFR) and ILC values for Daphnia magna. ILC values from the few laboratory studies of freshwater copepods ranged between 0.5 to 2.8 × 103 μg 1-1, and was higher than the ILC value of approximately 0.2 × 103 μg l-1 calculated for field populations of D. minutus. Generally, there was considerable agreement among laboratory studies regarding the shape of grazing-rate and ingestion-rate curves when data were converted to similar units and presented on standardized scales. © 1992 Kluwer Academic Publishers

Emergent global patterns of ecosystem structure and function from a mechanistic general ecosystem model

Anthropogenic activities are causing widespread degradation of ecosystems worldwide, threatening the ecosystem services upon which all human life depends. Improved understanding of this degradation is urgently needed to improve avoidance and mitigation measures. One tool to assist these efforts is predictive models of ecosystem structure and function that are mechanistic: based on fundamental ecological principles. Here we present the first mechanistic General Ecosystem Model (GEM) of ecosystem structure and function that is both global and applies in all terrestrial and marine environments. Functional forms and parameter values were derived from the theoretical and empirical literature where possible. Simulations of the fate of all organisms with body masses between 10 µg and 150,000 kg (a range of 14 orders of magnitude) across the globe led to emergent properties at individual (e.g., growth rate), community (e.g., biomass turnover rates), ecosystem (e.g., trophic pyramids), and macroecological scales (e.g., global patterns of trophic structure) that are in general agreement with current data and theory. These properties emerged from our encoding of the biology of, and interactions among, individual organisms without any direct constraints on the properties themselves. Our results indicate that ecologists have gathered sufficient information to begin to build realistic, global, and mechanistic models of ecosystems, capable of predicting a diverse range of ecosystem properties and their response to human pressures

Different prostate cancer bone metastasis models respond differently to treadmill exercise (Abstract only)

Background: Prostate cancer (PCa) is a leading cause of death in men with a predilection to metastasize into bone, when the disease is considered to be uncurable. Exercise has been suggested to improve the health of patients with PCa but no current studies on its effects on PCa bone metastasis. Hypothesis: Treadmill exercise can prevent the progression of PCa bone metastasis. Methods: Human xenograft PCa cell line PC3 and murine syngeneic RM1-BM cells were intracardiacally injected (~1x10 cells/injection) into BALB/c nude (n=8) and C57BL/6J mice (n=12), respectively. The following day, the mice were subjected to treadmill exercise (12 meters/minute, 5° inclination, 30 minutes/day, 5 days/week) for 3 weeks. Bioluminescence assay was used to track skeletal tumour growth weekly and micro-CT was used to analyse bone morphometrics ex vivo. Naïve mice (n>6) were subject to the same treadmill protocol and used to assess the osteogenic response. Animal procedures were ethically approved by The University of Sheffield, UK. Results: In the xenograft model, the treadmill exercised mice developed significantly higher tumour burden (p< 0.05, Mann-Whitney test) in their hindlimbs compared to sedentary controls. The bone structure was not improved by treadmill exercise according to micro-CT analysis. In contrast, the syngeneic model showed significantly lower tumour burden in exercised mice compared to controls (p< 0.05, Mann-Whitney test) and a tendency to significantly improved survival curve (p=0.07, Gehan-Breslow-Wilcoxon test). The trabecular thickness (Tb.Th) was found significantly higher compared to controls (p< 0.001, unpaired t-test). In the naïve baseline study, the trabecular BV/TV had a 7.5% increase in C57BL/6J but 8.5% reduction in BALB/c nude mice, compared between exercised to sedentary controls. Conclusion: Treadmill exercise alleviates PCa growth in bones of syngeneic RM1-BM/C57BL/6J but not the xenograft PC3/BALB/c nude model, a possible consequence of different osteogenic response to treadmill by the two mouse strains

Ingestion of Small-Bodied Zooplankton by Zebra Mussels (Dreissena polymorpha): Can Cannibalism on Larvae Influence Population Dynamics?

The zebra mussel Dreissena polymorpha established populations in western Lake Erie in 1986 and achieved densities exceeding 3.4 × 105 individuals∙m−2 during 1990. We assessed apparently incidental predation on Lake Erie and Erindale Pond zooplankton by adult mussels. Dreissena larvae and small rotifers (Polyarthra spp., Keratella spp., Trichocerca) sustained moderate to high predatory mortality whereas larger taxa (Bosmina, Scapholeberis) were invulnerable to predation. Larval Dreissena almost always sustain \u3e 99% mortality in European lakes. While mortality has been ascribed primarily to lack of suitable settling substrate and unfavourable environmental conditions, it may be confounded by larval predation by adults. We demonstrate using STELLA™-modelling that with a larval mortality rate of 99%, settled mussel densities observed in western Lake Erie during 1990 would not be achieved until at least 1994. A model that combines a lower rate (70%) of abiotic mortality with larval predation by adult mussels c..., Les populations de dreissena polymorphe (Dreissena polymorpha) déjà établies dans la partie ouest du lac Érié en 1986 atteignaient des densités supérieures à 3,4 × 105 individus par mètre carré au cours de 1990. Nous avons évalué Ta prédation du zooplancton du lac Érié et de l\u27étang Erindale par les dreissenas adultes. Les larves des dreissenas et les petits rotifères (Polyarthra spp., Keratella spp., Trichocerca) présentaient une mortalité par prédation variant de moyenne à élevée tandis que les plus gros taxons (Bosmima, Scapholeberis) résistaient à toute prédation. Les larves de Dreissena des lacs européeens présentent presque toujours un taux de mortalité supérieur à 99%. La mortalité a surtout été attribuée à l\u27absence d\u27un substrat de fixation adéquat et à des conditions environnementales défavorables, mais elle peut être confondue avec celle découlant de la prédation des larves par les adultes. Nous avons montré, à l\u27aide d\u27un modèle STELLAmd, que les densités de dreissenas fixées notées en 1990 n\u27..

Food storage facilitates professional religious specialization in hunter–gatherer societies

Professional religious specialists centralised religious authority in early human societies and represented some of the earliest instances of formalised social leadership. These individuals played a central role in the emergence of organised religion and transitions to more stratified human societies. Evolutionary theories highlight a range of environmental, economic and social factors that are potentially causally related to the emergence of professional religious specialists in human history. There remains little consensus over the relative importance of these factors and whether professional religious specialists were the outcome or driver of increased socio-cultural complexity. We built a global dataset of hunter–gatherer societies and developed a novel method of exploratory phylogenetic path analysis. This enabled us to systematically identify the factors associated with the emergence of professional religious specialists and infer the directionality of causal dependencies. We find that environmental predictability, environmental richness, pathogen load, social leadership and food storage systems are all correlated with professional religious specialists. However, only food storage is directly related to the emergence of professional religious specialists. Our findings are most consistent with the claim that the early stages of organised religion were the outcome rather than driver of increased socio-economic complexity.Introduction Methods and results Conclusio

Food storage facilitated the emergence of hunter-gatherer professional religious specialists

Professional religious specialists centralised religious authority in early human societies and represented some of the earliest instances of formalised social leadership. These individuals played a central role in the emergence of organised religion and transitions to more stratified human societies. Evolutionary theories highlight a range of environmental, economic and social factors that are potentially causally related to the emergence of professional religious specialists in human history. There remains little consensus over the relative importance of these factors and whether professional religious specialists were the outcome or driver of increased socio-cultural complexity. We built a global dataset of hunter–gatherer societies and developed a novel method of exploratory phylogenetic path analysis. This enabled us to systematically identify the factors associated with the emergence of professional religious specialists and infer the directionality of causal dependencies. We find that environmental predictability, environmental richness, pathogen load, social leadership and food storage systems are all correlated with professional religious specialists. However, only food storage is directly related to the emergence of professional religious specialists. Our findings are most consistent with the claim that the early stages of organised religion were the outcome rather than driver of increased socio-economic complexity

Sheldon Spectrum and the Plankton Paradox: Two Sides of the Same Coin : A trait-based plankton size-spectrum model

The Sheldon spectrum describes a remarkable regularity in aquatic ecosystems: the biomass density as a function of logarithmic body mass is approximately constant over many orders of magnitude. While size-spectrum models have explained this phenomenon for assemblages of multicellular organisms, this paper introduces a species-resolved size-spectrum model to explain the phenomenon in unicellular plankton. A Sheldon spectrum spanning the cell-size range of unicellular plankton necessarily consists of a large number of coexisting species covering a wide range of characteristic sizes. The coexistence of many phytoplankton species feeding on a small number of resources is known as the Paradox of the Plankton. Our model resolves the paradox by showing that coexistence is facilitated by the allometric scaling of four physiological rates. Two of the allometries have empirical support, the remaining two emerge from predator-prey interactions exactly when the abundances follow a Sheldon spectrum. Our plankton model is a scale-invariant trait-based size-spectrum model: it describes the abundance of phyto- and zooplankton cells as a function of both size and species trait (the maximal size before cell division). It incorporates growth due to resource consumption and predation on smaller cells, death due to predation, and a flexible cell division process. We give analytic solutions at steady state for both the within-species size distributions and the relative abundances across species