Active selection for large guppies, Poecilia reticulata, by the pike cichlid, Crenicichla saxatilis

Size-selective predation has been proposed to be one important evolutionary force shaping life-history traits in guppies ( Poecilia reticulata ). Populations living in the presence of the ring-tailed pike cichlid ( Crenicichla saxatilis ) are smaller, mature earlier, allocate more energy to offspring and get more and smaller young than guppies in localities without Crenicichla . We investigated if Crenicichla saxatilis is a size-selective predator, if the selectivity is a result of active choice and if the optimal prey size can be explained according to an optimal foraging model. In single-prey experiments we quantified the predators' pre-capture costs (time), capture success, and post-capture costs (time) for four different prey sizes spanning from 10 to 40 mm total length. To see which of the components of the prey cycle the predator takes into account for its choice, we then predicted prey values and optimal prey size with 6 different models that included one or more of the prey cycle components.
In two multiple prey experiments, the cichlids were given the choice of the two and four different prey sizes simultaneously. Crenicichla saxatilis actively selected the largest guppies in both cases. The three prey-value functions that included handling time (post-capture cost) did not accurately predict the prey choice. Instead the prey-value functions that took into account pre-capture cost (approach and attack time) were able to correctly predict the choice of the largest guppy size, suggesting that pre-capture costs may be more important than post-capture costs for prey choice in Crenicichla saxatilis . The study confirms that Crenicichla saxatilis is a size-selective predator selecting large guppies, while earlier evidence for selectivity for large prey in Crenicichla cichlids has been weak and equivocal. Our result strengthen the possibility that size-selective predation is a mechanism in life-history evolution in guppies.     

Monetary Valuation of Emissions in Implementing Environmental Policy

At various levels of environmental policy making there is a demand to translate polluting emissions into monetary units. In the so-called reduction cost approach, based upon policy targets, polluting emissions are expressed in monetary terms by determination of the marginal unit reduction cost at the emission target level. This approach provides shadow prices for emissions by which it can be established whether a certain measure or technology belongs to the most efficient set of measures by which the policy targets can be reached. This article argues that, if clear (generic) government targets such as national emission reduction targets exist for an emission, shadow prices derived by this method are to be preferred to shadow prices derived by other methods for decisions at the project (implementation) level. By application of the reduction cost approach, implementation decisions can be made that are both cost-effective and consistent with government policy.     

Characterization of the Tween 20-soluble membrane proteins of Acholephasma laidlawii

Methods for the purification of the four major proteins and two of the minor proteins in the Tween 20-soluble extract of A. laidlawii membranes have previously been described. The last step in the purification procedure involved an electrophoresis in a detergent-free buffer, where the concentration of Tween could be reduced by up to 2000 times. The purified proteins were found to remain soluble after removal of the bulk of the detergent. Solutions of the different protein samples contained 3 30 detergent molecules per protein molecule as determined by gas-liquid liquid chromatography. Some of the protein solutions also contained natural membrane lipids. It was probably only a fraction of detergent molecules and lipids, which was bound to the protein. Complete amino acid analysis showed that none of the proteins contained amino sugars and only one of them contained half-cystine. The specific absorbances and the molar absorption coefficients were calculated from the absorption spectra. The hydrophobicities and the partial specific volumes were calculated from the amino acid composition. The hydrophobicity values did not differ significantly from those of non-membrane proteins. Attempts to determine the sedimentation coefficients and the molecular weights were done ultracentrifugation after removal of the bulk of the detergent. The molecular weights, as determined by ultracentrifugation, were in general higher than the molecular weights determined by polyacrylamid-gel electrophoresis in sodium dodecyl sulphate (SDS), indicating that most of the proteins formed aggregates upon reducing the concentration of Tween 20. The size of these aggregates was not influenced by storage of the proteins at 0 C but it seemed to be highly affected by the speed and the time of centrifugation. The electrophoretic mobolities of the proteins were determined by free zone electrophoresis. Crossed immunoelectrophoresis was utilized to demonstrate that the Tween 20-soluble membrane proteins were not undergoing proteolysis during the preparation procedure.     

Foraging and community consequences of seed size for coexisting Negev Desert granivores

We examined the effects of seed size on patch use and diet selection for three co-existing Negev Desert granivores: Allenby's gerbil ( Gerbillus allenbyi ), greater Egyptian sand gerbil ( Gerbillus pyramidum ), and crested lark ( Galerida cristata ). We manipulated size and spatial distribution of seeds in experimental food patches and quantified foraging behavior by measuring giving-up densities (GUDs: the amount of food remaining in a resource patch following exploitation by a forager). In one experiment, we presented small (<1.4 mm in diameter cracked wheat), medium (2.0–3.3 mm), and large (>3.4 mm) seeds in separate trays; in a second, we presented small and medium seeds separately and mixed together. Gerbils had a higher handling time efficiency on smaller seeds, but a much higher encounter probability on larger seeds (20 times higher on large than medium seeds, and 2–5 times higher on medium than small seeds). This led gerbils to have significantly lower GUDs on larger seeds than smaller seeds and to harvest a higher proportion of the larger seeds. When presented with rich and poor patches, G. allenbyi tended to equalize GUDs in both patches, indicating a quitting harvest rate rule for patch exploitation. In contrast, larks appeared to use a fixed time rule for patch exploitation. For larks, seed size did not influence encounter probabilities, and they showed no seed-size selectivity. Still, larks had higher handling efficiencies on smaller than larger seeds, and consequently had a significantly lower GUD on small than medium seeds. Despite large differences between the gerbils and larks in their foraging, our results do not support species coexistence via seed-size partitioning: the larks had much higher GUDs than the gerbils on all seed sizes. Nonetheless, seed size, seed abundance, seed distribution and the animal's patch use behavior all played major roles in determining gerbils' and larks' diet selectivities and GUDs.     

Inhibition of human Chk1 causes increased initiation of DNA replication, phosphorylation of ATR targets, and DNA breakage

Human checkpoint kinase 1 (Chk1) is an essential kinase required to preserve genome stability. Here, we show that Chk1 inhibition by two distinct drugs, UCN-01 and CEP-3891, or by Chk1 small interfering RNA (siRNA) leads to phosphorylation of ATR targets. Chk1-inhibition triggered rapid, pan-nuclear phosphorylation of histone H2AX, p53, Smc1, replication protein A, and Chk1 itself in human S-phase cells. These phosphorylations were inhibited by ATR siRNA and caffeine, but they occurred independently of ATM. Chk1 inhibition also caused an increased initiation of DNA replication, which was accompanied by increased amounts of nonextractable RPA protein, formation of single-stranded DNA, and induction of DNA strand breaks. Moreover, these responses were prevented by siRNA-mediated downregulation of Cdk2 or the replication initiation protein Cdc45, or by addition of the CDK inhibitor roscovitine. We propose that Chk1 is required during normal S phase to avoid aberrantly increased initiation of DNA replication, thereby protecting against DNA breakage. These results may help explain why Chk1 is an essential kinase and should be taken into account when drugs to inhibit this kinase are considered for use in cancer treatment.     

Epidermal growth factor receptor dimerization and activation require ligand-induced conformational changes in the dimer interface

Structural studies have shown that ligand-induced epidermal growth factor receptor (EGFR) dimerization involves major domain rearrangements that expose a critical dimerization arm. However, simply exposing this arm is not sufficient for receptor dimerization, suggesting that additional ligand-induced dimer contacts are required. To map these contributions to the dimer interface, we individually mutated each contact suggested by crystallographic studies and analyzed the effects on receptor dimerization, activation, and ligand binding. We find that domain II contributes >90% of the driving energy for dimerization of the extracellular region, with domain IV adding little. Within domain II, the dimerization arm forms much of the dimer interface, as expected. However, a loop from the sixth disulfide-bonded module (immediately C-terminal to the dimerization arm) also makes a critical contribution. Specific ligand-induced conformational changes in domain II are required for this loop to contribute to receptor dimerization, and we identify a set of ligand-induced intramolecular interactions that appear to be important in driving these changes, effectively "buttressing" the dimer interface. Our data also suggest that similar conformational changes may determine the specificity of ErbB receptor homo- versus heterodimerization.     

Distinct requirements for Pot1 in limiting telomere length and maintaining chromosome stability

The fission yeast Pot1 (protection of telomeres) protein binds to the single-stranded extensions at the ends of telomeres, where its presence is critical for the maintenance of linear chromosomes. Homologs of Pot1 have been identified in a wide variety of eukaryotes, including plants, animals, and humans. We now show that Pot1 plays dual roles in telomere length regulation and chromosome end protection. Using a series of Pot1 truncation mutants, we have defined distinct areas of the protein required for chromosome stability and for limiting access to telomere ends by telomerase. We provide evidence that a large portion of Pot1, including the N-terminal DNA binding domain and amino acids close to the C terminus, is essential for its protective function. C-terminal Pot1 fragments were found to exert a dominant-negative effect by displacing endogenous Pot1 from telomeres. Reducing telomere-bound Pot1 in this manner resulted in dramatic lengthening of the telomere tract. Upon further reduction of Pot1 at telomeres, the opposite phenotype was observed: loss of telomeric DNA and chromosome end fusions. Our results demonstrate that cells must carefully regulate the amount of telomere-bound Pot1 to differentiate between allowing access to telomerase and catastrophic loss of telomeres.     

A calorimetric study on the binding of six general anesthetics to the hydrophobic core of a model protein

The thermodynamic parameters underlying the binding of six volatile general anesthetics to the hydrophobic core of the four-alpha-helix bundle (Aalpha(2)-L38M)(2) are determined using isothermal titration calorimetry. Chloroform, bromoform, trichloroethylene, benzene, desflurane and fluroxene are shown to bind to the four-alpha-helix bundle with dissociation constants of 880+/-10, 90+/-5, 200+/-10, 900+/-30, 220+/-10 and 790+/-40 microM, respectively. The measured dissociation constants for the binding of the six general anesthetics to the four-alpha-helix bundle (Aalpha(2)-L38M)(2) correlate with their human or animal EC(50) values. The negative enthalpy changes indicate that favorable polar interactions are achieved between bound anesthetic and the adjacent amino acid side chains. Because of its small size and the ability to bind a variety of general anesthetics, the four-alpha-helix bundle (Aalpha(2)-L38M)(2) represents an attractive system for structural studies on anesthetic-protein complexes.     

A hybrid systems framework for cellular processes

With the availability of technologies that allow us to obtain stimulus-response time series data for modeling and system identification, there is going to be an increasing need for conceptual frameworks in which to formulate and test hypotheses about intra- and inter-cellular dynamics, in general and not just dependent on a particular cell line, cell type, organism, or technology. While the semantics can be quite different, biologists and systems scientists use in many cases a similar language (notion of feedback, regulation, etc.). A more abstract system-theoretic framework for signals, systems, and control could provide the biologist with an interface between the domains. Apart from recent examples to identify functional elements and describing them in engineering terms, there have been various more abstract developments to describe dynamics at the cell level in the past. This includes Rosen's (M,R)-systems. This paper presents an abstract and general compact mathematical framework of intracellular dynamics, regulation and regime switching inspired by (M,R)-theory and based on hybrid automata.