bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation of cognitive pharmaceutical services in Danish community pharmacies — perceptions of strategists and practitioners
Authors: Hopp Trine R , Klinke Bjørn O , Sørensen Ellen W , Herborg Hanne , Roberts Alison S
Published: February 2006

Objective

To understand how projects for the implementation of cognitive pharmaceutical services (CPS) are perceived as facilitators of change from the perspectives of practitioners and strategists. Setting Sixteen community pharmacies in Denmark and three organisations working on implementing CPS in pharmacy practice.

Method

Twenty semi-structured interviews were conducted with practitioners (pharmacy staff and owners) in ‘professionally active’ pharmacies, and eight interviews were conducted with ‘professional strategists’ in the field of pharmacy practice. Informants were asked about their goals for participation in and development of projects regarding implementation of CPS, and about change strategies used for implementation. An interview guide based on organisational theory was used, and an organisational theory framework formed the basis of the analysis.

Key findings

Eleven goals for the development of projects relating to CPS implementation from the strategist's perspective were identified. From the practitioners' perspective, nine goals for participation in such projects were identified. The two groups share four categories of goals regarding: competence development; implementation of CPS; marketing of the pharmacy; and improvement of patients' drug use and outcomes. Other goals from the two perspectives predominantly differ from each other.

Two metaphors were developed as images of the two different ways of perceiving CPS projects. The strategists develop projects as ‘standard menus’, and the practitioners select projects in which to participate as if they were one of many dishes on a ‘buffet’.

Strategies for change were also identified. The humanistic change strategy predominated from both groups of informants' perspective.

Conclusion

While they have some goals in common, there is a clear difference in the perspectives of strategists and practitioners in the development of and participation in CPS-related projects. The metaphors ‘standard menu’ and ‘buffet’ are two ways of understanding implementation. If these metaphors are accepted as a premise in the field of pharmacy practice, future work with implementation of CPS should take these differences into account.
Evaluation of a decision aid and a personal risk profile in community pharmacy for patients considering options to improve cardiovascular health: the OPTIONS pilot study
Authors: Lalonde Lyne , O'Connor Annette M , Duguay Pierrette , Brassard Joëlle , Drake Elizabeth , Grover Steven A
Published: February 2006

Objective

In a pilot study, to assess the feasibility and relevance of providing a community pharmacist consultation supplemented by a decision aid (DA) or a personal risk profile (PRP) to patients on lipid-lowering or antihypertensive pharmacotherapy. Preliminary data on the clinical effectiveness of these interventions were collected.

Method

Patients were randomised to DA or PRP and evaluated before, two weeks after, and three months after a pharmacist consultation. No differences were observed between DA and PRP groups; results are reported for all patients combined. The quality of the patients' decision to initiate or maintain lifestyle change and/or pharmacological treatment was evaluated at baseline and two weeks after the consultation by measuring their knowledge, risk perception, decisional conflict and satisfaction with the decision process. The stage of change for various lifestyles and changes in cardiovascular disease (CVD)-risk factors were evaluated at baseline and at three months. Setting Ten community pharmacies.

Key findings

Twenty-six of 42 patients (62%) agreed to participate. Patients reported as excellent or very good the way the information was presented (79%), the amount of information (88%), and the usefulness of the tools (100%). The quality of the patients' decision at baseline was low; one-third of participants correctly estimated their CVD risks and laboratory results, and 54% had high decisional conflict. After the intervention, the satisfaction scores for role in decision making, amount of information provided and pharmacist's attitude were 69%, 81% and 85% respectively, and the proportion of participants with high decisional conflict declined to 25% (P = 0.02). CVD knowledge and risk perception did not change after the intervention. Improvements in low-density lipoprotein cholesterol (LDL)-C, total-C/high-density lipoprotein (HDL)-C ratio, body mass index, and estimated 10-year CVD risk were observed.

Conclusion

Providing pharmacist consultation supplemented by a DA or a PRP in community pharmacies is feasible and relevant. However, it did not improve CVD knowledge or risk perception.
Exploring the dissonance between business and public health policy: pharmacy and the provision of opioid pharmacotherapies and clean needles in rural settings
Authors: Le Phuong-Phi , Hotham Elizabeth D
Published: February 2006

Objective

To ascertain, by interview of rural community pharmacists, how well public health policies relating to the provision of clean needles and opioid pharmacotherapies fit with the imperatives of business. Previous research investigating the provision of opioid pharmacotherapies focused predominantly on metropolitan community pharmacists and their experience with servicing methadone clients. Furthermore, there had been no exploration as to whether dissonance exists between community pharmacy business imperatives and the public health policy underpinning these programmes.

Method

Fifteen rural community pharmacists were interviewed in three focus groups. Experienced interviewer and researcher EH facilitated all three focus group interviews. The questioning path was developed following review of the literature. Thematic analysis identified common themes and issues within the qualitative data collected.

Setting

All three focus group interviews were conducted in rural South Australia.

Key findings

Professional obligation played a key role in motivating rural community pharmacists to be involved with service provision. Dissonance existed between the sense of fulfilment by participating in a major public health initiative and the recognition of the mainly negative financial impacts. Financial gain was limited, due to difficulty in fee collection, and inadequate remuneration. Other difficulties included lack of support from allied health services, and restricted access to training due to geographical isolation.

Conclusion

Some of the difficulties experienced in the servicing of opioid-dependent clients and its clash with business imperatives are universal and not specific to a rural environment. For the provision of opioid pharmacotherapy services to have fruitful business outcomes and simultaneously deliver effective services, appropriate remuneration and support programmes are needed. Future initiatives should aim at improving pharmacist communications with allied health services and prescribing doctors, as well as greater training opportunities to address problems associated with geographical isolation. Training on realistic outcomes of opioid treatment, the philosophy of treatment, and whether the role should include reducing client doses to assist clients become ‘drug free’ were identified as relevant training issues.
Delivering a home-based medication review, process measures from the HOMER randomised controlled trial
Authors: Holland Richard , Lenaghan Elizabeth , Smith Richard , Lipp Alistair , Christou Maria , Evans David , Harvey Ian
Published: February 2006

Objectives

The HOme-based MEdication Review (HOMER) trial investigated whether home-based medication review by pharmacists could decrease hospital re-admission in older people. This trial demonstrated that the intervention increased admissions by 30% (P=0.009). This unexpected finding provoked significant interest. This paper describes the intervention in detail and the process measures recorded by review pharmacists, and investigates whether results differed according to pharmacist characteristics.

Method

437 patients were randomised to the intervention, which involved two pharmacist home visits within two and eight weeks of discharge, and 435 were randomised to usual care. An analysis was undertaken of the process measures and to determine whether admission rates differed within the intervention group according to the type of pharmacist performing the review. Setting Norfolk or Suffolk patients aged over 80 years discharged to their own home after an emergency admission (any cause), and taking two or more medications daily.

Key findings

Twenty-two pharmacists participated. The majority (68%) were experienced community pharmacists (mean age = 42 years), 71% had a postgraduate qualification. Pharmacists identified adverse drug reactions in 33% of patients and made a mean of 1.6 recommendations/comments per visit undertaken. At least 35% of these were enacted. Pharmacists reduced inappropriate drug storage from 7% to 2% of visited patients by their second visit (P = 0.04), and reduced hoarding of unnecessary drugs from 40% of visited patients to 19% (P < 0.001). Finally, the rate of admission within the intervention group did not vary significantly according to experience or type of pharmacist delivering the intervention.

Conclusion

The HOMER intervention was conducted in a similar way to interventions in many other medication review studies. Given the HOMER trial's counter-intuitive findings it is clear that there is an urgent need to refine this intervention, identify the most suitable location for its delivery, and develop training that can ensure it is delivered to best effect.
Photocatalytic Activities of Rh-doped CaTiO3 under Visible Light Irradiation
Authors: Nishimoto Shunsuke , Matsuda Motohide , Miyake Michihiro
Published: February 2006

The effect of cation substitution into CaTiO3 has been investigated. Rh-doped CaTiO3 showed intense absorption in the visible light region (λ > 420 nm), and was found to be a new photocatalyst for H2 evolution from an aqueous methanol solution under visible light irradiation.
Self-organization of Patterned CaCO3/Polymer Composite Films: Tuning of Their Morphologies by the Change of Molecular Weights of Acidic Polymers
Authors: Sakamoto Takeshi , Oichi Akira , Sugawara Ayae , Kato Takashi
Published: February 2006

Calcium carbonate (CaCO3) thin films with periodic surface patterns are formed on thin film matrices of a polysaccharide derivative from a solution containing poly(acrylic acid) (PAA). The morphologies of the patterned films have been tuned by the change of molecular weights of the PAA.
Highly Ordered Pt-loaded CdS Nanowire Arrays for Photocatalytic Hydrogen Production under Visible Light
Authors: Bao Ningzhong , Shen Liming , Takata Tsuyoshi , Lu Daling , Domen Kazunari
Published: February 2006

Highly ordered crystalline Pt-loaded CdS nanowire arrays were prepared using a hard template of mesoporous silica and show good photocatalytic activity for hydrogen production under visible-light irradiation.
Formation of Dented Poly(methyl methacrylate)/Poly(styrene-co-divinylbenzene) Composite Particles in Seeded Soap-free Emulsion Copolymerization
Authors: Shi Shan , Hayami Hiroaki , Kuroda Shin-ichi , Kubota Hitoshi
Published: February 2006

Nonspherical composite particles having multiple dents on particle surface were synthesized for the first time by seeded soap-free emulsion copolymerization of styrene and divinylbenzene (crosslinker) on spherical, linear poly(methyl methacrylate) seed particles. The number and depth of the dents were controllable by varying polymerization formulation.
Hexagonal Columnar Superstructure Generated by Compact Liquid-crystalline Molecules Possessing Disk-shape, C3-Symmetry, and Ionic Bonding Sites
Authors: Katoh Masaki , Uehara Satoshi , Kohmoto Shigeo , Kishikawa Keiki
Published: February 2006

Small C3-symmetric supramolecules, 1:3 complexes of tri(2-aminoethyl)amine (1) and 3,4,5-trialkoxybenzoic acid (2c–2n, R = (CH2)n−1CH3, n = 5–16) generated a stable hexagonal columnar phase. The phase behaviors, stoichiometry, supramolecular structure, and superstructure were investigated.
Pathway HUDs: Are They Viable?
Authors: Fadden Steven , Ververs Patricia May , Wickens Christopher D.
Published: February 2006

We describe two experiments that examine 3D pathway displays in a head-up location for aircraft landing and taxi. We address both guidance performance and pilot strategies in dividing, focusing, and allocating attention between flight path information and event monitoring. In Experiment 1 the 3D pathway head-up display (HUD) was compared with a conventional 2D HUD. The former was found to produce better guidance, with few costs to event detection. Some evidence was provided that attentional tunneling of the pathway HUD inhibits the detection of unexpected traffic events. In Experiment 2, the pathway display was compared in a head-up versus a head-down location. Excellent guidance was achieved in both locations. A slight HUD cost for vertical tracking in the air was offset by a HUD benefit for event detection and for lateral tracking during taxi (i.e., on the ground). The results of both experiments are interpreted within the framework of object- and space-based theories of visual attention and point to the conclusion that pathway HUDs combine the independent advantages of pathways and HUDs, particularly during ground operations. Actual or potential applications include understanding the costs and benefits of positioning a 3D pathway display
Haptic Force-Feedback Devices for the Office Computer: Performance and Musculoskeletal Loading Issues
Authors: Dennerlein Jack Tigh , Yang Maria C.
Published: February 2006

Pointing devices, essential input tools for the graphical user interface (GUI) of desktop computers, require precise motor control and dexterity to use. Haptic force-feedback devices provide the human operator with tactile cues, adding the sense of touch to existing visual and auditory interfaces. However, the performance enhancements, comfort, and possible musculoskeletal loading of using a force-feedback device in an office environment are unknown. Hypothesizing that the time to perform a task and the self-reported pain and discomfort of the task improve with the addition of force feedback, 26 people ranging in age from 22 to 44 years performed a point-and-click task 540 times with and without an attractive force field surrounding the desired target. The point-and-click movements were approximately 25% faster with the addition of force feedback (paired t-tests, p < 0.001). Perceived user discomfort and pain, as measured through a questionnaire, were also smaller with the addition of force feedback (p < 0.001). However, this difference decreased as additional distracting force fields were added to the task environment, simulating a more realistic work situation. These results suggest that for a given task, use of a force-feedback device improves performance, and potentially reduces musculoskeletal loading during mouse use. Actual or potential applications of this research include human-computer interface design, specifically that of the pointing device extensively used for the graphical user interface.
Incidental Memory and Navigation in Panoramic Virtual Reality for Electronic Commerce
Authors: Howes Andrew , Miles Gareth E. , Payne Stephen J. , Mitchell Christabel D. , Davies Anthony J.
Published: February 2006

Recently much effort has been dedicated to designing and implementing World Wide Web sites for virtual shopping and e-commerce. Despite this effort, relatively little empirical work has been done to determine the effectiveness with which different site designs sell products. We report three experiments in which participants were asked to search for products in various experimental e-commerce sites. Across the experiments participants were asked to search in either QTVR (QuickTime Virtual Reality), hypertext, or pictorially rich hypertext environments; they were then tested for their ability to recall the products seen and to recognize product locations. The experiments demonstrated that when using QTVR (Experiments 1, 2, and 3) or pictorial environments (Experiment 2), participants retained more information about products that were incidental to their goals. In two of the experiments it was shown that participants navigated more efficiently when using a QTVR environment. The costs and benefits of using 3D virtual environments for on-line shops are discussed. Actual or potential applications of this research include support for the development of e-commerce design guidelines.
Auditory Localization under Sustained +Gz Acceleration
Authors: Nelson W. Todd , Bolia Robert S. , Trip Lloyd D.
Published: February 2006

The ability to localize a virtual sound source in the horizontal plane was evaluated under varying levels of sustained (+Gz) acceleration. Participants were required to judge the locations of spatialized noise bursts in the horizontal plane (elevation 0°) during exposure to 1.0, 1.5, 2.5, 4.0, 5.5, and 7.0 +Gz. The experiment was conducted at the U.S. Air Force Research Laboratory's Dynamic Environment Simulator, a three-axis centrifuge. No significant increases in localization error were found between 1.0 and 5.5 +Gz; however, a significant increase did occur at the 7.0 +Gz level. In addition, the percentage of front/back confusions did not vary as a function of +Gz level. Collectively, these results indicate that the ability to localize virtual sound sources is well maintained at various levels of sustained acceleration. Actual or potential applications include the incorporation of spatial audio displays into the human-computer interface for vehicles that are operated in acceleration environments.
Management by Consent in Human-Machine Systems: When and Why It Breaks Down
Authors: Olson Wesley A. , Sarter Nadine B.
Published: February 2006

This study examined the effects of conflict type, time pressure, and display design on operators' ability to make informed decisions about proposed machine goals and actions in a management-by-consent context. A group of 30 B757 pilots were asked to fly eight descent scenarios while responding to a series of air traffic control clearances. Each scenario presented pilots with a different conflict that arose from either incompatible goals contained in the clearance or inappropriate implementation of the clearance by automated flight deck systems. Pilots were often unable to detect these conflicts, especially under time pressure, and thus failed to disallow or intervene with proposed machine actions. Detection performance was particularly poor for conflicts related to clearance implementation. These conflicts were most likely to be missed when automated systems did more than the pilot expected of them. Performance and verbal protocol data indicate that the observed difficulties can be explained by a combination of poor system feedback and pilots' difficulties with generating expectations of future system behavior. Our results are discussed in terms of their implications for the choice and implementation of automation management strategies in general and, more specifically, with respect to risks involved in envisioned forms of digital air-ground communication in the future aviation system. Actual or potential applications of this research include the design of future data link systems and procedures, as well as the design of future automated systems in any domain that rely on operator consent as a mechanism for human-machine coordination.
Menu Design with Visual Momentum for Compact Smart Products
Authors: Tang Kuo-Hao E.
Published: February 2006

Users of compact smart products with small screens often have trouble learning the menu structure. If they cannot master the menu structure, users are not able to fully utilize the products. It is argued in this paper that using visual momentum in menu representation design helps users develop effective mental maps of menu structures and promotes learning of the user interface. To assess the effect of visual momentum in this study, four types of menu representations were developed. Additionally, two menu hierarchies, two types of function key layout, and two types of function key labeling were assessed to examine the effects of menu dimension and compatibility. Experimental results indicated that participants using a partial menu map with visual momentum design performed the best, and participants using a partial menu map without visual momentum performed the poorest, even worse than those-using command-only representation. The results also showed that the menu navigation problem appeared to be particularly significant with a deep menu hierarchy. Actual or potential applications of this research include menu representation design for compact smart products.
Visual Search for Traffic Signs: The Effects of Clutter, Luminance, and Aging
Authors: Ho Geoffrey , Scialfa Charles T. , Caird Jeff K. , Graw Trevor
Published: February 2006

Latency and eye movement measures were used to examine the effects of aging, clutter, and luminance on visual search for traffic signs embedded in digitized images of driving scenes. Initially 14 older and 14 younger observers classified daytime and nighttime traffic scenes as containing low or high amounts of clutter. Next, an independent sample of 14 younger and 14 older participants searched for traffic signs contained within these scenes. Errors were more common among the elderly. Search efficiency declined with increased clutter and with aging. However, relative to the young, older adults did not suffer disproportionately as a result of increased clutter. The methods developed might be profitably employed to assess sign conspicuity and sign acquisition during driving.
Use of Warnings in an Attentionally Demanding Detection Task
Authors: Maltz Masha , Meyer Joachim
Published: February 2006

The study assessed the use of binary warnings in a detection task with high attentional demands. Participants in the experiment had to decide whether to continue or halt production based on a briefly displayed number that indicated a temperature level. The short time that the number was displayed required that participants focus on the display area. Participants were rewarded for production when the system was intact and were heavily penalized for decisions to produce under dangerous temperature levels. Color-coded warning cues (green for safe, red for danger) were displayed to the participants prior to number presentation. The experimental conditions differed in the validity of the cue and in the probability of red cues. Results showed significant learning for all conditions. Participants tended to ignore the nonvalid and low-validity cues and rely only on highly valid cues. However, the mere existence of cues affected participants' general tendency to take risks. Actual or potential applications of this research include improving systems that require operators to devote attention to complex tasks while receiving and responding to warnings.
Effect of Computer Keyboard Slope and Height on Wrist Extension Angle
Authors: Simoneau Guy G. , Marklin Richard W.
Published: February 2006

The goal of this study was to determine the systematic effect that varying the slope angle of a computer keyboard along with varying keyboard height (relative to elbow height) have on wrist extension angle while typing. Thirty participants typed on a keyboard whose slope was adjusted to +15°, +7.5°, 0°, -7.5°, and -15°. The height of the keyboard was set up such that participants' wrists were at the same height as their elbows, above their elbows, and four cm below their elbows. Results showed that as keyboard slope angle moved downward from +15° to -15°, mean wrist extension decreased approximately 13° (22° at +15° slope to 9° at -15° slope). Keyboard height had a similar effect with mean wrist extension decreasing from 21.8° when the keyboard was lower than elbow height, to 7.3° when the keyboard was higher than elbow height. Potential application of this research includes the downward sloping of computer keyboards, which could possibly be beneficial in the prevention of musculoskeletal disorders affecting the wrist
Multichannel Auditory Search: Toward Understanding Control Processes in Polychotic Auditory Listening
Authors: Lee Mark D.
Published: February 2006

Two experiments are presented that serve as a framework for exploring auditory information processing. The framework is referred to as polychotic listening or auditory search, and it requires a listener to scan multiple simultaneous auditory streams for the appearance of a target word (the name of a letter such as A or M). Participants' ability to scan between two and six simultaneous auditory streams of letter and digit names for the name of a target letter was examined using six loudspeakers. The main independent variable was auditory load, or the number of active audio streams on a given trial. The primary dependent variables were target localization accuracy and reaction time. Results showed that as load increased, performance decreased. The performance decrease was evident in reaction time, accuracy, and sensitivity measures. The second study required participants to practice the same task for 10 sessions, for a total of 1800 trials. Results indicated that even with extensive practice, performance was still affected by auditory load. The present results are compared with findings in the visual search literature. The implications for the use of multiple auditory displays are discussed. Potential applications include cockpit and automobile warning displays, virtual reality systems, and training systems.
Mapping Density Response in Maize: A Direct Approach for Testing Genotype and Treatment Interactions
Authors: Gonzalo Martin , Vyn Tony J , Holland James B , McIntyre Lauren M
Published: February 2006

Maize yield improvement has been strongly linked to improvements in stress tolerance, particularly to increased interplant competition. As a result, modern hybrids are able to produce kernels at high plant population densities. Identification of the genetic factors responsible for density response in maize requires direct testing of interactions between genetic effects and density and evaluation of that response in multiple traits. In this article we take a broad view of the problem and use a general approach based upon mixed models to analyze data from eight segmental inbred lines in a B73 background and their crosses to the unrelated parent Mo17 (hybrids). We directly test for the interaction between treatment effects and genetic effects instead of the commonly used overlaying of results on a common map. Additionally, we demonstrate one way to handle heteroscedasticity of variances common in stress responses. We find that some SILs are consistently different from the recurrent parent regardless of the density, while others differ from the recurrent parent in one density level but not in the other. Thus, we find positive evidence for both main effects and interaction between genetic loci and density in cases where the approach of overlapping results fails to find significant results. Furthermore, our study clearly identifies segments that respond differently to density depending upon the inbreeding level (inbred/hybrid).
Using Genetic Markers to Directly Estimate Gene Flow and Reproductive Success Parameters in Plants on the Basis of Naturally Regenerated Seedlings
Authors: Burczyk J , Adams W T , Birkes D S , Chybicki I J
Published: February 2006

Estimating seed and pollen gene flow in plants on the basis of samples of naturally regenerated seedlings can provide much needed information about “realized gene flow,” but seems to be one of the greatest challenges in plant population biology. Traditional parentage methods, because of their inability to discriminate between male and female parentage of seedlings, unless supported by uniparentally inherited markers, are not capable of precisely describing seed and pollen aspects of gene flow realized in seedlings. Here, we describe a maximum-likelihood method for modeling female and male parentage in a local plant population on the basis of genotypic data from naturally established seedlings and when the location and genotypes of all potential parents within the population are known. The method models female and male reproductive success of individuals as a function of factors likely to influence reproductive success (e.g., distance of seed dispersal, distance between mates, and relative fecundity–i.e., female and male selection gradients). The method is designed to account for levels of seed and pollen gene flow into the local population from unsampled adults; therefore, it is well suited to isolated, but also wide-spread natural populations, where extensive seed and pollen dispersal complicates traditional parentage analyses. Computer simulations were performed to evaluate the utility and robustness of the model and estimation procedure and to assess how the exclusion power of genetic markers (isozymes or microsatellites) affects the accuracy of the parameter estimation. In addition, the method was applied to genotypic data collected in Scots pine (isozymes) and oak (microsatellites) populations to obtain preliminary estimates of long-distance seed and pollen gene flow and the patterns of local seed and pollen dispersal in these species.
Two- and Three-Locus Tests for Linkage Analysis Using Recombinant Inbred Lines
Authors: Martin Olivier C , Hospital Frédéric
Published: February 2006

We consider fixed recombinant inbred lines (RILs) derived either by selfing or by full-sib mating; when applicable, we also consider intermated recombinant inbreds (IRIs). First, we show that the usual estimate of recombination fraction based on RIL data is biased, and we provide an estimate where the major part of that bias is removed. Second, we derive simple formulas to compute the frequencies of genotypes at three loci in RILs. We describe the nonindependence of multiple recombinations arising in RIL recombination data even though there may be no interference in each meiosis. Finally, we give formulas for interference tests, gene mapping, or QTL detection in RIL populations.
A Simple and Robust Statistical Test for Detecting the Presence of Recombination
Authors: Bruen Trevor C , Philippe Hervé , Bryant David
Published: February 2006

Recombination is a powerful evolutionary force that merges historically distinct genotypes. But the extent of recombination within many organisms is unknown, and even determining its presence within a set of homologous sequences is a difficult question. Here we develop a new statistic, Φw, that can be used to test for recombination. We show through simulation that our test can discriminate effectively between the presence and absence of recombination, even in diverse situations such as exponential growth (star-like topologies) and patterns of substitution rate correlation. A number of other tests, Max χ2, NSS, a coalescent-based likelihood permutation test (from LDHat), and correlation of linkage disequilibrium (both r2 and |D′|) with distance, all tend to underestimate the presence of recombination under strong population growth. Moreover, both Max χ2 and NSS falsely infer the presence of recombination under a simple model of mutation rate correlation. Results on empirical data show that our test can be used to detect recombination between closely as well as distantly related samples, regardless of the suspected rate of recombination. The results suggest that Φw is one of the best approaches to distinguish recurrent mutation from recombination in a wide variety of circumstances.
The Influence of Hitchhiking and Deleterious Mutation Upon Asexual Mutation Rates
Authors: Palmer Michael E , Lipsitch Marc
Published: February 2006

The question of how natural selection affects asexual mutation rates has been considered since the 1930s, yet our understanding continues to deepen. The distribution of mutation rates observed in natural bacteria remains unexplained. It is well known that environmental constancy can favor minimal mutation rates. In contrast, environmental fluctuation (e.g., at period T) can create indirect selective pressure for stronger mutators: genes modifying mutation rate may “hitchhike” to greater frequency along with environmentally favored mutations they produce. This article extends a well-known model of Leigh to consider fitness genes with multiple mutable sites (call the number of such sites α). The phenotypic effect of such a gene is enabled if all sites are in a certain state and disabled otherwise. The effects of multiple deleterious loci are also included (call the number of such loci γ). The analysis calculates the indirect selective effects experienced by a gene inducing various mutation rates for given values of α, γ, and T. Finite-population simulations validate these results and let us examine the interaction of drift with hitchhiking selection. We close by commenting on the importance of other factors, such as spatiotemporal variation, and on the origin of variation in mutation rates.
Alignment of the Genomes ofBrachypodium distachyonand Temperate Cereals and Grasses Using Bacterial Artificial Chromosome Landing With Fluorescencein SituHybridization
Authors: Hasterok Robert , Marasek Agnieszka , Donnison Iain S , Armstead Ian , Thomas Ann , King Ian P , Wolny Elzbieta , Idziak Dominika , Draper John , Jenkins Glyn
Published: February 2006

As part of an initiative to develop Brachypodium distachyon as a genomic “bridge” species between rice and the temperate cereals and grasses, a BAC library has been constructed for the two diploid (2n = 2x = 10) genotypes, ABR1 and ABR5. The library consists of 9100 clones, with an approximate average insert size of 88 kb, representing 2.22 genome equivalents. To validate the usefulness of this species for comparative genomics and gene discovery in its larger genome relatives, the library was screened by PCR using primers designed on previously mapped rice and Poaceae sequences. Screening indicated a degree of synteny between these species and B. distachyon, which was confirmed by fluorescent in situ hybridization of the marker-selected BACs (BAC landing) to the 10 chromosome arms of the karyotype, with most of the BACs hybridizing as single loci on known chromosomes. Contiguous BACs colocalized on individual chromosomes, thereby confirming the conservation of genome synteny and proving that B. distachyon has utility as a temperate grass model species alternative to rice.
Clonal Interference and the Periodic Selection of New Beneficial Mutations in Escherichia coli
Authors: de Visser J Arjan G M , Rozen Daniel E
Published: February 2006

The conventional model of adaptation in asexual populations implies sequential fixation of new beneficial mutations via rare selective sweeps that purge all variation and preserve the clonal genotype. However, in large populations multiple beneficial mutations may co-occur, causing competition among them, a phenomenon called “clonal interference.” Clonal interference is thus expected to lead to longer fixation times and larger fitness effects of mutations that ultimately become fixed, as well as to a genetically more diverse population. Here, we study the significance of clonal interference in populations consisting of mixtures of differently marked wild-type and mutator strains of Escherichia coli that adapt to a minimal-glucose environment for 400 generations. We monitored marker frequencies during evolution and measured the competitive fitness of random clones from each marker state after evolution. The results demonstrate the presence of multiple beneficial mutations in these populations and slower and more erratic invasion of mutants than expected by the conventional model, showing the signature of clonal interference. We found that a consequence of clonal interference is that fitness estimates derived from invasion trajectories were less than half the magnitude of direct estimates from competition experiments, thus revealing fundamental problems with this fitness measure. These results force a reevaluation of the conventional model of periodic selection for asexual microbes.
Induced Paternal Effects Mimic Cytoplasmic Incompatibility in Drosophila
Authors: Clark Michael E , Heath Benjamin D , Anderson Cort L , Karr Timothy L
Published: February 2006

Wolbachia is an intracellular microbe found in a wide diversity of arthropod and filarial nematode hosts. In arthropods these common bacteria are reproductive parasites that manipulate central elements of their host's reproduction to increase their own maternal transmission in one of several ways. Cytoplasmic incompatibility (CI) is one such manipulation where sperm are somehow modified in infected males and this modification must be rescued by the presence of the same bacterial strain in the egg for normal development to proceed. The molecular mechanisms involved in the expression of CI are unknown. Here we show that Wolbachia infection results in increased mRNA and protein expression of the Drosophila simulans nonmuscle myosin II gene zipper. Induced overexpression of zipper in Wolbachia-free transgenic D. melanogaster males results in paternal-effect lethality that mimics the fertilization defects associated with CI. Likewise, overexpression of the tumor suppressor gene, lethal giant larvae [l(2)gl], results in egg lethality and a CI phenotype. Stoichiometric levels of zipper and l(2)gl are required for proper segregation of cellular determinants during neuroblast stem cell division. Taken together these results form the basis of a working hypothesis whereby Wolbachia induces paternal effects in sperm by manipulating the expression of key regulators of cytoskeletal activity during spermatogenesis.
Multiple Events Are Responsible for an Insertion in a Paternally Inherited Mitochondrial Genome of the Mussel Mytilus galloprovincialis
Authors: Mizi Athanasia , Zouros Eleftherios , Rodakis George C
Published: February 2006

In a sperm-transmitted mtDNA of Mytilus galloprovincialis we found an insertion that is not present in the typical genome and whose origin can be explained by a sequence of three events: a tandem duplication, a nonhomologous recombination, and a deletion. Unless such events are extremely rare in this species, the identical gene arrangement of the two gender-specific genomes should imply strong selection for same gene order and size.
High-Resolution Quantitative Trait Locus Mapping Reveals Sign Epistasis Controlling Ovariole Number Between Two Drosophila Species
Authors: Orgogozo Virginie , Broman Karl W , Stern David L
Published: February 2006

Identifying the genes underlying genetically complex traits is of fundamental importance for medicine, agriculture, and evolutionary biology. However, the level of resolution offered by traditional quantitative trait locus (QTL) mapping is usually coarse. We analyze here a trait closely related to fitness, ovariole number. Our initial interspecific mapping between Drosophila sechellia (8 ovarioles/ovary) and D. simulans (15 ovarioles/ovary) identified a major QTL on chromosome 3 and a minor QTL on chromosome 2. To refine the position of the major QTL, we selected 1038 additional recombinants in the region of interest using flanking morphological markers (selective phenotyping). This effort generated approximately one recombination event per gene and increased the mapping resolution by approximately seven times. Our study thus shows that using visible markers to select for recombinants can efficiently increase the resolution of QTL mapping. We resolved the major QTL into two epistatic QTL, QTL3a and QTL3b. QTL3a shows sign epistasis: it has opposite effects in two different genetic backgrounds, the presence vs. the absence of the QTL3b D. sechellia allele. This property of QTL3a allows us to reconstruct the probable order of fixation of the QTL alleles during evolution.
Male Demography in East Asia: A North–South Contrast in Human Population Expansion Times
Authors: Xue Yali , Zerjal Tatiana , Bao Weidong , Zhu Suling , Shu Qunfang , Xu Jiujin , Du Ruofu , Fu Songbin , Li Pu , Hurles Matthew E , Yang Huanming , Tyler-Smith Chris
Published: February 2006

The human population has increased greatly in size in the last 100,000 years, but the initial stimuli to growth, the times when expansion started, and their variation between different parts of the world are poorly understood. We have investigated male demography in East Asia, applying a Bayesian full-likelihood analysis to data from 988 men representing 27 populations from China, Mongolia, Korea, and Japan typed with 45 binary and 16 STR markers from the Y chromosome. According to our analysis, the northern populations examined all started to expand in number between 34 (18–68) and 22 (12–39) thousand years ago (KYA), before the last glacial maximum at 21–18 KYA, while the southern populations all started to expand between 18 (6–47) and 12 (1–45) KYA, but then grew faster. We suggest that the northern populations expanded earlier because they could exploit the abundant megafauna of the “Mammoth Steppe,” while the southern populations could increase in number only when a warmer and more stable climate led to more plentiful plant resources such as tubers.
Analysis of Core Housekeeping and Virulence Genes Reveals Cryptic Lineages ofClostridium perfringensThat Are Associated With Distinct Disease Presentations
Authors: Rooney Alejandro P , Swezey James L , Friedman Robert , Hecht David W , Maddox Carol W
Published: February 2006

Clostridium perfringens is an important human and animal pathogen that causes a number of diseases that vary in their etiology and severity. Differences between strains regarding toxin gene composition and toxin production partly explain why some strains cause radically different diseases than others. However, they do not provide a complete explanation. The purpose of this study was to determine if there is a phylogenetic component that explains the variance in C. perfringens strain virulence by assessing patterns of genetic polymorphism in genes (colA gyrA, plc, pfoS, and rplL) that form part of the core genome in 248 type A strains. We found that purifying selection plays a central role in shaping the patterns of nucleotide substitution and polymorphism in both housekeeping and virulence genes. In contrast, recombination was found to be a significant factor only for the virulence genes plc and colA and the housekeeping gene gyrA. Finally, we found that the strains grouped into five distinct evolutionary lineages that show evidence of host adaptation and the early stages of speciation. The discovery of these previously unknown lineages and their association with distinct disease presentations carries important implications for human and veterinary clostridial disease epidemiology and provides important insights into the pathways through which virulence has evolved in C. perfringens.
A Deficiency in the Region Homologous to Human 17q21.33–q23.2 Causes Heart Defects in Mice
Authors: Yu Y Eugene , Morishima Masae , Pao Annie , Wang Ding-Yan , Wen Xiao-Yan , Baldini Antonio , Bradley Allan
Published: February 2006

Several constitutional chromosomal rearrangements occur on human chromosome 17. Patients who carry constitutional deletions of 17q21.3–q24 exhibit distinct phenotypic features. Within the deletion interval, there is a genomic segment that is bounded by the myeloperoxidase and homeobox B1 genes. This genomic segment is syntenically conserved on mouse chromosome 11 and is bounded by the mouse homologs of the same genes (Mpo and HoxB1). To attain functional information about this syntenic segment in mice, we have generated a 6.9-Mb deletion [Df(11)18], the reciprocal duplication [Dp(11)18] between Mpo and Chad (the chondroadherin gene), and a 1.8-Mb deletion between Chad and HoxB1. Phenotypic analyses of the mutant mouse lines showed that the Dp(11)18/Dp(11)18 genotype was responsible for embryonic or adolescent lethality, whereas the Df(11)18/+ genotype was responsible for heart defects. The cardiovascular phenotype of the Df(11)18/+ fetuses was similar to those of patients who carried the deletions of 17q21.3–q24. Since heart defects were not detectable in Df(11)18/Dp(11)18 mice, the haplo-insufficiency of one or more genes located between Mpo and Chad may be responsible for the abnormal cardiovascular phenotype. Therefore, we have identified a new dosage-sensitive genomic region that may be critical for normal heart development in both mice and humans.
Cotransport of the Heterodimeric Small Subunit of the Saccharomyces cerevisiae Ribonucleotide Reductase Between the Nucleus and the Cytoplasm
Authors: An Xiuxiang , Zhang Zhen , Yang Kui , Huang Mingxia
Published: February 2006

Ribonucleotide reductase (RNR) catalyzes the rate-liming step in de novo deoxyribonucleotide biosynthesis and is essential in DNA replication and repair. Cells have evolved complex mechanisms to modulate RNR activity during normal cell cycle progression and in response to genotoxic stress. A recently characterized mode of RNR regulation is DNA damage-induced RNR subunit redistribution. The RNR holoenzyme consists of a large subunit, R1, and a small subunit, R2. The Saccharomyces cerevisiae R2 is an Rnr2:Rnr4 heterodimer. Rnr2 generates a diferric–tyrosyl radical cofactor required for catalysis; Rnr4 facilitates cofactor assembly and stabilizes the resulting holo-heterodimer. Upon DNA damage, Rnr2 and Rnr4 undergo checkpoint-dependent, nucleus-to-cytoplasm redistribution, resulting in colocalization of R1 and R2. Here we present evidence that Rnr2 and Rnr4 are transported between the nucleus and the cytoplasm as one protein complex. Tagging either Rnr2 or Rnr4 with a nuclear export sequence causes cytoplasmic localization of both proteins. Moreover, mutations at the Rnr2:Rnr4 heterodimer interface can affect the localization of both proteins without disrupting the heterodimeric complex. Finally, the relocalization of Rnr4 appears to involve both active export and blockage of nuclear import. Our findings provide new insights into the mechanism of DNA damage-induced RNR subunit redistribution.
Selective Male Mortality in the Red Imported Fire Ant, Solenopsis invicta
Authors: Fritz Gary N , Vander Meer Robert K , Preston Catherine A
Published: February 2006

Males in polygyne populations of Solenopsis invicta are primarily sterile diploids and thought to not express the Gp-9 gene coding for a pheromone-binding protein affecting complex social behavior. We examined an aspect of the breeding system hitherto not considered—male Gp-9 genotypes in relation to sperm stored in queens. Four sites with varying frequencies of sympatric monogyne and polygyne colonies were sampled, including sexuals, workers, and broods from four colonies. Most queens were heterozygotes storing B sperm. Although predicted to be common, only 14 of 504 males were B or BB genotypes, suggesting strong selection. Increased frequency of polygyne colonies at each site paralleled increases in queens with b sperm (1.9–32.8%) and of noninseminated queens. The presence of both B and b sperm in 1.9–18.9% of queens, genotype profiles of colonies, and genotypes of offspring from individual queens suggest some frequency of multiple mating. The bb genotype, rather than an obligate, developmental lethal, was present in some queens and common in alates, workers, and brood. Selective mortality of sexuals may affect multiple aspects of the breeding system, including female-mediated dispersal, mating success, and gene flow.