A “parallel plate” electrostatic model for bimolecular rate constants applied to electron transfer proteins

A “parallel plate” model describing the electrostatic potential energy of protein-protein interactions is presented that provides an analytical representation of the effect of ionic strength on a bimolecular rate constant. The model takes into account the asymmetric distribution of charge on the surface of the protein and localized charges at the site of electron transfer that are modeled as elements of a parallel plate condenser. Both monopolar and dipolar interactions are included. Examples of simple (monophasic) and complex (biphasic) ionic strength dependencies obtained from experiments with several electron transfer protein systems are presented, all of which can be accommodated by the model. The simple cases do not require the use of both monopolar and dipolar terms (i.e., they can be fit well by either alone). The biphasic dependencies can be fit only by using dipolar and monopolar terms of opposite sign, which is physically unreasonable for the molecules considered. Alternatively, the high ionic strength portion of the complex dependencies can be fit using either the monopolar term alone or the complete equation; this assumes a model in which such behavior is a consequence of electron transfer mechanisms involving changes in orientation or site of reaction as the ionic strength is varied. Based on these analyses, we conclude that the principal applications of the model presented here are to provide information about the structural properties of intermediate electron transfer complexes and to quantify comparisons between related proteins or site-specific mutants. We also conclude that the relative contributions of monopolar and dipolar effects to protein electron transfer kinetics cannot be evaluated from experimental data by present approximations.     

Extreme storms cause rapid but short-lived shifts in nearshore subtropical bacterial communities

Climate change scenarios predict tropical cyclones will increase in both frequency and intensity, which will escalate the amount of terrestrial run-off and mechanical disruption affecting coastal ecosystems. Bacteria are key contributors to ecosystem functioning, but relatively little is known about how they respond to extreme storm events, particularly in nearshore subtropical regions. In this study, we combine field observations and mesocosm experiments to assess bacterial community dynamics and changes in physicochemical properties during early- and late-season tropical cyclones affecting Okinawa, Japan. Storms caused large and fast influxes of freshwater and terrestrial sediment – locally known as red soil pollution – and caused moderate increases of macronutrients, especially SiO₂ and PO₄³⁻, with up to 25 and 0.5 μM respectively. We detected shifts in relative abundances of marine and terrestrially derived bacteria, including putative coral and human pathogens, during storm events. Soil input alone did not substantially affect marine bacterial communities in mesocosms, indicating that other components of run-off or other storm effects likely exert a larger influence on bacterial communities. The storm effects were short-lived and bacterial communities quickly recovered following both storm events. The early- and late-season storms caused different physicochemical and bacterial community changes, demonstrating the context-dependency of extreme storm responses in a subtropical coastal ecosystem.     

Characterization of sterically stabilized cisplatin liposomes by nuclear magnetic resonance

Extensive scientific efforts are directed towards finding new and improved platinum anticancer agents. A promising approach is the encapsulation of cisplatin in sterically stabilized, long circulating, PEGylated 100 nm liposomes. This liposomal cisplatin (STEALTH cisplatin, formerly known as SPI-77) shows excellent stability in plasma and has a longer circulation time, greater efficacy and lower toxicity than much free cisplatin. However, so far, the physicochemical characterization of STEALTH cisplatin has been limited to size distribution, drug-to-lipid ratio and stability. Information on the physical state of the drug in the liposome aqueous phases and the drug's interaction with the liposome membrane has been lacking. This study was aimed at filling this gap. We report a multinuclear NMR study in which several techniques have been used to assess the physical nature of cisplatin in liposomal formulations and if and to what extent the drug affects the liposome phospholipids. Since NMR detects only the soluble cisplatin in the liposomes and not the insoluble drug, combining NMR and atomic absorption data enables one to determine how much of the encapsulated drug is soluble in the intraliposomal aqueous phase. Our results indicate that almost all of the cisplatin remains intact during the loading process, and that the entire liposomal drug is present in a soluble form in the internal aqueous phase of the liposomes.     

A Simple Genetic Architecture Underlies Morphological Variation in Dogs

Domestic dogs exhibit tremendous phenotypic diversity, including a greater variation in body size than any other terrestrial mammal. Here, we generate a high density map of canine genetic variation by genotyping 915 dogs from 80 domestic dog breeds, 83 wild canids, and 10 outbred African shelter dogs across 60,968 single-nucleotide polymorphisms (SNPs). Coupling this genomic resource with external measurements from breed standards and individuals as well as skeletal measurements from museum specimens, we identify 51 regions of the dog genome associated with phenotypic variation among breeds in 57 traits. The complex traits include average breed body size and external body dimensions and cranial, dental, and long bone shape and size with and without allometric scaling. In contrast to the results from association mapping of quantitative traits in humans and domesticated plants, we find that across dog breeds, a small number of quantitative trait loci (≤3) explain the majority of phenotypic variation for most of the traits we studied. In addition, many genomic regions show signatures of recent selection, with most of the highly differentiated regions being associated with breed-defining traits such as body size, coat characteristics, and ear floppiness. Our results demonstrate the efficacy of mapping multiple traits in the domestic dog using a database of genotyped individuals and highlight the important role human-directed selection has played in altering the genetic architecture of key traits in this important species.     

Toxicity,behavior impairment,and repellence of essential oils from pepper‐rosmarin and patchouli to termites

Plant essential oils are potential sources of insecticidal compounds, but have rarely been explored for their effect on termites. In the present study, we assessed the chemical composition of essential oils of Lippia sidoides Cham. (pepper‐rosmarin; Verbenaceae) and Pogostemon cablin (Blanco) Benth. (patchouli; Lamiacaeae) and evaluated their toxicity, behavioral impairment, and repellence to termite species of the genera Amitermes and Microcerotermes (Isoptera: Termitidae: Termitinae). The main components of essential oils of L. sidoides and P. cablin were thymol (44.6%) and patchouli alcohol (36.6%), respectively. The essential oil of P. cablin was most potent against Amitermes cf. amifer Silvestri and had the lowest LD₅₀ (0.63 μg mg^?1). There was no difference in toxicity for Microcerotermes indistinctus Mathews between the essential oils of L. sidoides (LD₅₀ = 1.49 μg mg^?1) and P. cablin (LD₅₀ = 1.67 μg mg^?1). Pogostemon cablin essential oil was the most toxic to M. indistinctus (LC₅₀ = 0.32 μl ml^?1) and A. cf. amifer (LC₅₀ = 0.29 μl ml^?1). The essential oils analyzed exhibited high toxicity and repellence to the termites, in addition to reducing behavioral interactions among individuals, thus constituting potential termiticides.     

Playing chicken with red junglefowl: identifying phenotypic markers of genetic purity in Gallus gallus

We report the results of a novel experiment, in which genetically pure male red junglefowl Gallus gallus (Richardson strain) were deliberately crossed with domestic female chickens to create contaminated lines of known purity, reaching as high as 93.75%. Phenotypic characters generally used as indicators of purity (reduced or absent female comb, male eclipse plumage, etc.) all appeared to at least some extent in domestically contaminated progeny and moreso in successively more pure generations of the experiment, suggesting that such phenotypic characters may have little, if any, utility in characterizing red junglefowl stocks as to their genetic purity.     

The Economic impact of ME/CFS: Individual and societal costs

Background

ME/CFS is characterized by debilitating fatigue in addition to other physical and cognitive symptoms. It is estimated to affect over 800,000 adults in the U.S. ME/CFS often results in diminished functionality and increased economic impact. The economic impact of an illness is generally divided into two categories: direct and indirect costs. Despite high prevalence rates and the disabling nature of the illness, few studies have examined the costs of ME/CFS at the individual and societal level. In fact, of the four studies examining the economic impact of ME/ME/CFS only two used a U. S. sample. The current study used community and tertiary samples to examine the direct costs of ME/CFS.

Methods

Using archival data, Study 1 examined the direct cost of ME/CFS in a community-based sample in Chicago. Study 2 estimated the direct cost of ME/CFS in a tertiary sample in Chicago. Both Study1 and Study 2 assessed direct costs using office visit costs, medical test costs, and medication costs.

Results

For Study 1, the annual direct total cost per ME/CFS patient was estimated to be $2,342, with the total annual direct cost of ME/CFS to society being approximately $2 billion. In Study 2, the annual direct was estimated to be $8,675 per ME/CFS patient, with the total annual direct cost of ME/CFS to society being approximately $7 billion.

Conclusion

Using ME/CFS prevalence data of 0.42 and indirect costs estimates from Reynolds et al. (2004), the direct and indirect cost of ME/CFS to society was estimated to be $18,677,912,000 for the community sample and $23,972,300,000 for the tertiary sample. These findings indicate that whether or not individuals are recruited from a community or tertiary sample, ME/CFS imposes substantial economic costs.

     

Foraging ecology of the endangered wood stork recorded in the stable isotope signature of feathers

Down feathers and regurgitant were collected from nestling wood storks (Mycteria americana) from two inland and two coastal breeding colonies in Georgia. The stable isotopic ratios of carbon (¹³C/¹²C) and nitrogen (¹⁵N/¹⁴N) in these materials were analyzed to gain insights into the natal origins of juvenile storks and the foraging activities of adults. Down feathers differed in '¹³C between inland and coastal colonies, having average isotopic values that reflected the sources of carbon fixed in biomass at the base of the food web. Feathers from the inland colonies differed between colonies in '¹⁵N, while those from the coastal colonies did not. These patterns primarily reflected the foraging activities of parent storks, with individuals capturing differing percentages of prey of distinct trophic status at each colony. Collectively, the carbon and nitrogen isotopic signatures of feather keratin were used to distinguish nestlings from each colony, except for instances where storks from different colonies foraged in common wetlands. The stable isotopic composition of food items in regurgitant was used to reconstruct the trophic structure of the ecosystems in which wood storks foraged. Predicted foraging activities based on the isotopic composition of keratin were generally consistent with the percentage of prey types (freshwater vs. saltwater and lower trophic level vs. upper trophic level consumer) observed in regurgitant, except for the coastal colony at St. Simons Island, where the '¹³C of feathers strongly suggested that freshwater prey were a significant component of the diet. This inconsistency was resolved by aerial tracking of adults during foraging excursions using a fixed-wing aircraft. Observed foraging activities supported interpretations based on the stable isotope content of feathers, suggesting that the latter provided a better record of overall foraging activity than regurgitant analysis alone. Observed foraging patterns were compared to the predictions of a statistical model that determined habitat utilization based on habitat availability using a geographic information system (GIS) database. Observed foraging activities and those predicted from feathers both suggested that some adult storks preferred to feed their young freshwater prey, even when saltwater resources were more accessible in the local environment. This conclusion supports the contention that wood stork populations are sensitive to changes in the distribution of freshwater habitats along the southeastern coastal plain of the United States.