bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasmodium falciparum glucose‐6‐phosphate dehydrogenase 6‐phosphogluconolactonase is a potential drug target
Authors: Allen Stacey M. , Lim Erin E. , Jortzik Esther , Preuss Janina , Chua Hwa Huat , MacRae James I. , Rahlfs Stefan , Haeussler Kristina , Downton Matthew T. , McConville Malcolm J. , Becker Katja , Ralph Stuart A. 
Published: July 2015

The malarial parasite Plasmodium falciparum is exposed to substantial redox challenges during its complex life cycle. In intraerythrocytic parasites, haemoglobin breakdown is a major source of reactive oxygen species. Deficiencies in human glucose‐6‐phosphate dehydrogenase, the initial enzyme in the pentose phosphate pathway (PPP), lead to a disturbed redox equilibrium in infected erythrocytes and partial protection against severe malaria. In P. falciparum, the first two reactions of the PPP are catalysed by the bifunctional enzyme glucose‐6‐phosphate dehydrogenase 6‐phosphogluconolactonase (PfGluPho). This enzyme differs structurally from its human counterparts and represents a potential target for drugs. In the present study we used epitope tagging of endogenous PfGluPho to verify that the enzyme localises to the parasite cytosol. Furthermore, attempted double crossover disruption of the PfGluPho gene indicates that the enzyme is essential for the growth of blood stage parasites. As a further step towards targeting PfGluPho pharmacologically, ellagic acid was characterised as a potent PfGluPho inhibitor with an IC50 of 76 nm. Interestingly, pro‐oxidative drugs or treatment of the parasites with H2O2 only slightly altered PfGluPho expression or activity under the conditions tested. Furthermore, metabolic profiling suggested that pro‐oxidative drugs do not significantly perturb the abundance of PPP intermediates. These data indicate that PfGluPho is essential in asexual parasites, but that the oxidative arm of the PPP is not strongly regulated in response to oxidative challenge.
Ecological research and management of intermittent rivers: an historical review and future directions
Authors: Leigh Catherine , Boulton Andrew J. , Courtwright Jennifer L. , Fritz Ken , May Christine L. , Walker Richard H. , Datry Thibault 
Published: July 2015

SummaryRivers and streams that do not flow permanently (herein intermittent rivers;IRs) make up a large proportion of the world's inland waters and are gaining widespread attention. We review the research onIRs from its early focus on natural history through to current application in management and policy.The few early studies of the ecology ofIRs were largely descriptive. Nevertheless, in the 1970s, synthesis of this sparse research complemented work on temporary standing waters to found a powerful framework for much of the subsequent research onIRs.Research on the ecology and biogeochemistry ofIRs continues to fuel our understanding of resistance and resilience to drying and flooding as disturbances. Syntheses of the growing literature, including cross‐continental and cross‐climate comparisons, are revealing the generality and individuality of ecological and ecosystem responses to flow cessation and surface water loss. Meanwhile, increasing numbers of experiments test the causality of these responses.Much of the increased consideration ofIRs in research, management and policy is driven by the observed and projected shifts in flow regimes from perennial to intermittent associated with changes in land and water use and climate, superimposed on the high incidence of natural intermittency. The need to protect and better manageIRs is prompting researchers to develop new or modified methods to monitor flow status and assess the ecological condition of these systems.Intermittent river research and management will benefit from greater exploration of aquatic–terrestrial linkages, wet–dry cycling and temporal dynamics, more‐detailed mapping and predictive modelling of flow intermittency and the application of metapopulation and metacommunity concepts alongside multiple‐stressors and novel‐ecosystems research. By building on existing knowledge, continuing to develop quantitative models and distribution maps and using experiments to test hypotheses and concepts, we can further ecological understanding and wise management of these ubiquitous ecosystems.
Plant Location Patterns in the European Automobile Supplier Industry
Authors: Klier Thomas , McMillen Daniel 
Published: July 2015

AbstractMotor vehicle and motor vehicle parts production tend to exhibit a strong degree of agglomeration. We estimate a location model utilizing detailed plant‐level data for over 1,700 European locations of the largest motor vehicle parts suppliers, as well as the location of all light vehicle assembly plants operational in 2010. This unique data set allows us to estimate a location model for the region at a significantly higher level of resolution than the previous literature. The results suggest that the main forces of agglomeration in the European auto supplier sector are highway access and the desire to locate near assembly plants as well as near other parts‐producing plants.
The State‐Level Impacts of Enforcing Sales Taxes for E‐retail Purchases
Authors: Conroy Tessa , Cutler Harvey , Weiler Stephan 
Published: July 2015

AbstractThe Marketplace Fairness Act (S. 743) recently passed by the U.S. Senate may portend a national move toward states imposing sales taxes for business‐to‐consumer e‐retail purchases. While much of the policy debate surrounding this question has focused on trade creation versus diversion, there are likely distinct compositional effects at the state level, which will affect both economic activity and tax revenue. Consumers are clearly hurt by an online sales tax. However, such a policy would seemingly benefit state tax coffers, as well as traditional brick‐and‐mortar retailers and their employees. This paper uses a computable general equilibrium model approach to get a better understanding of the state‐level income, employment, and tax revenue effects of such a policy shift, in particular the likely tradeoffs between these three traditional economic targets across reasonable ranges of price elasticities.
“You know your own fistula, it becomes a part of you”—Patient perspectives on vascular access: A semistructured interview study
Authors: Taylor Matthew J. , Hanson Camilla S. , Casey Jordan R. , Craig Jonathan C. , Harris David , Tong Allison 
Published: July 2015

AbstractThe success of hemodialysis depends on functional vascular access but such an invasive, semipermanent intervention can be confronting for patients. Vascular access complications are potentially life threatening and reduce treatment satisfaction and quality of life. This study aims to describe patient perspectives on vascular access. Face‐to‐face, semistructured interviews were conducted with 26 adult patients receiving hemodialysis with any form of vascular access at two dialysis units in Australia. The transcripts were analyzed using thematic analysis. We identified five major themes describing patient perspectives on vascular access: developing mental fortitude for access (accepting necessity for survival, self‐advocacy, experiential confidence and competency, dependency on others, gaining vascular knowledge), device intrusiveness on the body (restricting normal function, finding compensatory solutions, bodily invasion, confronting appearance), inhibiting pain (aversion to surgery, persisting needle anxieties), exposure to dire health consequences (resigning to inevitable failure, anticipating serious complications, technological skepticism, wary of medical incompetence), and imposing burdens (generating additional expenses, encumbering family members). Patients with a vascular access rely on a precarious lifeline, which is confronting, intrusive, and burdensome. Some develop mental resilience to cope with the pain and invasiveness of vascular access. The results suggest that more attention to address needle anxieties, self‐advocacy, lifestyle disruption, fear of complications, and concern for caregiver burden may improve treatment satisfaction and outcomes for patients on hemodialysis.
The dental pulp stem cell niche based on aldehyde dehydrogenase 1 expression
Authors: Machado C. V. , Passos S. T. , Campos T. M. C. , Bernardi L. , Vilas‐Bôas D. S. , Nör J. E. , Telles P. D. S. , Nascimento I. L. 
Published: July 2015

AbstractAimTo detect cells expressing the stem cell marker ALDH1 (aldehyde dehydrogenase1) in the pulp of human permanent teeth and to investigate the expression of ALDH1 in isolated dental pulp cells.MethodologyPulp tissue was collected and processed for immunohistochemistry to detect ALDH1‐, STRO‐1‐ and CD90‐positive cells. In addition, cells were isolated and analysed by flow cytometry for ALDH1 activity and for the cell surface markers CD44, CD73, CD90, STRO‐1 and CD45. Cells were also examined for multidifferentiation capacity. Within these cells, an ALDH1+ cell subpopulation was selected and evaluated for multidifferentiation capacity.ResultsThe immunohistochemistry analyses showed that ALDH1‐, CD90‐ and STRO‐1‐positive cells were located mainly in the perivascular areas and nerve fibres of dental pulps. Cells on the fifth passage had high expression for CD44, CD73 and CD90, whereas moderate labelling was observed for STRO‐1 and ALDH1 in flow cytometry analysis. On the same passages, cells were able to differentiate into osteogenic, adipogenic and chondrogenic lineages. The ALDH1+ cell subpopulation also demonstrated multilineage differentiation ability.ConclusionsDental pulp stem cells reside in the vicinity of blood vessels and nerve fibres, indicating the possible existence of more than one stem cell niche in dental pulps. Furthermore, ALDH1 was expressed by isolated dental pulp cells, which had mesenchymal stem cell characteristics. Thus, it can be suggested that ALDH1 may be used as a DPSC marker.
Porosity and sealing ability of root fillings with gutta‐percha and BioRoot RCS or AH Plus sealers. Evaluation by three ex vivo methods
Authors: Viapiana R. , Moinzadeh A. T. , Camilleri L. , Wesselink P. R. , Tanomaru Filho M. , Camilleri J. 
Published: July 2015

AbstractAimTo investigate the ability of BioRoot RCS, a tricalcium silicate‐based root canal sealer and AH Plus to effectively fill the root canals of contralateral teeth using three evaluation methods, and to investigate also the correlation between the methods.MethodologyThe prepared root canals of ten pairs of contralateral mandibular premolar teeth were filled with gutta‐percha and sealer using lateral compaction. The percentage of voids within the root canal was assessed by micro‐computed tomography, whilst sealing ability was investigated by fluid transport and leakage of fluorescent microspheres. The interaction of sealer with dentine, and sealer penetration were assessed by confocal microscopy. The void volume, fluid flow, microsphere leakage and sealer interaction with dentine for both materials were compared. Nonparametric (Mann–Whitney) tests were used to compare the % void and fluid transport of the two sealers. Spearman correlation was used to assess the pairwise relationships between the techniques. The level of significance was set to 0.05.ResultsBioRoot RCS exhibited significantly more percentage of voids than AH Plus. There was no difference in fluid flow and microsphere penetration. BioRoot RCS exhibited a different pattern of sealer penetration and interaction with the dentine walls compared to AH Plus. For both materials, the pairwise correlations between the three techniques were close to zero, indicating weak relationships.ConclusionsMicroCT analysis revealed a higher void volume for BioRoot RCS. The other techniques did not show a difference between the sealing ability of the sealers. The correlation between the three ex vivo methods of assessment was weak demonstrating their complementarity rather than their concordance.
Effects of pathogen exposure on life‐history variation in the gypsy moth (Lymantria dispar)
Authors: Páez D. J. , Fleming‐Davies A. E. , Dwyer G. 
Published: July 2015

AbstractInvestment in host defences against pathogens may lead to trade‐offs with host fecundity. When such trade‐offs arise from genetic correlations, rates of phenotypic change by natural selection may be affected. However, genetic correlations between host survival and fecundity are rarely quantified. To understand trade‐offs between immune responses to baculovirus exposure and fecundity in the gypsy moth (Lymantria dispar), we estimated genetic correlations between survival probability and traits related to fecundity, such as pupal weight. In addition, we tested whether different virus isolates have different effects on male and female pupal weight. To estimate genetic correlations, we exposed individuals of known relatedness to a single baculovirus isolate. To then evaluate the effect of virus isolate on pupal weight, we exposed a single gypsy moth strain to 16 baculovirus isolates. We found a negative genetic correlation between survival and pupal weight. In addition, virus exposure caused late‐pupating females to be identical in weight to males, whereas unexposed females were 2–3 times as large as unexposed males. Finally, we found that female pupal weight is a quadratic function of host mortality across virus isolates, which is likely due to trade‐offs and compensatory growth processes acting at high and low mortality levels, respectively. Overall, our results suggest that fecundity costs may strongly affect the response to selection for disease resistance. In nature, baculoviruses contribute to the regulation of gypsy moth outbreaks, as pathogens often do in forest‐defoliating insects. We therefore argue that trade‐offs between host life‐history traits may help explain outbreak dynamics.
Context‐dependent effects of Y chromosome and mitochondrial haplotype on male locomotive activity in Drosophila melanogaster
Authors: Dean R. , Lemos B. , Dowling D. K. 
Published: July 2015

AbstractSome regions of the genome exhibit sexual asymmetries in inheritance and are thus subjected to sex‐biased evolutionary forces. Maternal inheritance of mitochondrial DNA (mtDNA) enables mtDNA mutations harmful to males, but not females, to accumulate. In the face of male‐harmful mtDNA mutation accumulation, selection will favour the evolution of compensatory modifiers in the nuclear genome that offset fitness losses to males. The Y chromosome is a candidate to host these modifiers, because it is paternally inherited, known to harbour an abundance of genetic variation for male fertility, and therefore likely to be under strong selection to uphold male viability. Here, we test for intergenomic interactions involving mtDNA and Y chromosomes in male Drosophila melanogaster. Specifically, we examine effects of each of these genomic regions, and their interaction, on locomotive activity, across different environmental contexts – both dietary and social. We found that both the mtDNA haplotype and Y chromosome haplotype affected activity in males assayed in an environment perceived as social. These effects, however, were not evident in males assayed in perceived solitary environments, and neither social nor solitary treatments revealed evidence for intergenomic interactions. Finally, the magnitude and direction of these genetic effects was further contingent on the diet treatment of the males. Thus, genes within the mtDNA and Y chromosome are involved in genotype‐by‐environment interactions. These interactions might contribute to the maintenance of genetic variation within these asymmetrically inherited gene regions and complicate the dynamics of genetic interactions between the mtDNA and the Y chromosome.
Terminal investment in the gustatory appeal of nuptial food gifts in crickets
Authors: Duffield K. R. , Hunt J. , Rapkin J. , Sadd B. M. , Sakaluk S. K. 
Published: July 2015

AbstractInvestment in current versus future reproduction represents a prominent trade‐off in life‐history theory and is likely dependent on an individual's life expectancy. The terminal investment hypothesis posits that a reduction in residual reproductive value (i.e. potential for future offspring) will result in increased investment in current reproduction. We tested the hypothesis that male decorated crickets (Gryllodes sigillatus), when cued to their impending mortality, should increase their reproductive effort by altering the composition of their nuptial food gifts (i.e. spermatophylaxes) to increase their gustatory appeal to females. Using a repeated‐measures design, we analysed the amino acid composition of spermatophylaxes derived from males both before and after injection of either a saline control or a solution of heat‐killed bacteria. The latter, although nonpathogenic, represents an immune challenge that may signal an impending survival threat. One principal component explaining amino acid variation in spermatophylaxes, characterized by a high loading to histidine, was significantly lower in immune‐challenged versus control males. The relevance of this difference for the gustatory appeal of gifts to females was assessed by mapping spermatophylax composition onto a fitness surface derived in an earlier study identifying the amino acid composition of spermatophylaxes preferred by females. We found that immune‐challenged males maintained the level of attractiveness of their gifts post‐treatment, whereas control males produced significantly less attractive gifts post‐injection. These results are consistent with the hypothesis that cues of a survival‐threatening infection stimulate terminal investment in male decorated crickets with respect to the gustatory appeal of their nuptial food gifts.
Loss of adaptation following reversion suggests trade‐offs in host use by a seed beetle
Authors: Messina F. J. , Durham S. L. 
Published: July 2015

AbstractExperimental evolution has provided little support for the hypothesis that the narrow diets of herbivorous insects reflect trade‐offs in performance across hosts; selection lines can sometimes adapt to an inferior novel host without a decline in performance on the ancestral host. An alternative approach for detecting trade‐offs would be to measure adaptation decay after selection is relaxed, that is, when populations newly adapted to a novel host are reverted to the ancestral one. Lines of the seed beetle Callosobruchus maculatus rapidly adapted to a poor host (lentil); survival in lentil seeds increased from 2% to > 90% in < 30 generations. After the lines had reached a plateau with respect to survival in lentil, sublines were reverted to the ancestral host, mung bean. Twelve generations of reversion had little effect on performance in lentil, but after 25–35 generations, the reverted lines exhibited lower survival, slower development and smaller size. The most divergent pair of lines was then assayed on both lentil and mung bean. Performance on lentil was again much poorer in the reverted line than in the nonreverted one, but the lines performed equally well on mung bean. Moreover, the performance of the nonreverted line on mung bean remained comparable to that of the original mung‐bean population. Our results thus present a paradox: loss of adaptation to lentil following reversion implies a trade‐off, but the continued strong performance of lentil‐adapted lines on mung bean does not. Genomic comparisons of the reverted, nonreverted and ancestral lines may resolve this paradox and determine the importance of selection vs. drift in causing a loss of adaptation following reversion.
Comparative Effectiveness of Chemotherapy Regimens in Prolonging Survival for Two Large Population‐Based Cohorts of Elderly Adults with Breast and Colon Cancer in 1992–2009
Authors: Du Xianglin L. , Zhang Yefei , Parikh Rohan C. , Lairson David R. , Cai Yi 
Published: July 2015

ObjectivesTo compare the effectiveness of chemotherapy in prolonging survival according to age in breast and colon cancer.DesignRetrospective cohort study with a matched cohort analysis based on the conditional probability of receiving chemotherapy.SettingThe 16 Surveillance, Epidemiology, and End Results (SEER) areas from the SEER‐Medicare linked database.ParticipantsWomen diagnosed with Stage I to IIIa hormone receptor–negative breast cancer (n = 14,440) and 26,893 men and women with Stage III colon cancer (n = 26,893) aged 65 and older in 1992 to 2009.MeasurementsThe main exposure was the receipt of chemotherapy, and the main outcome was mortality.ResultsIn women with breast cancer aged 65 to 69, the risk of all‐cause mortality was statistically significantly lower in those who received chemotherapy than in those who did not in the entire cohort (hazard ratio (HR) = 0.70, 95% confidence interval (CI) = 0.57–0.88) and in a propensity‐matched cohort (HR = 0.82, 95% CI = 0.70–0.96) after adjusting for measured confounders. These patterns were similar in participants aged 70 to 74 and 75 to 79, but in women aged 80 to 84 and 85 to 89, risk of all‐cause mortality was no longer significantly lower in those receiving chemotherapy in the entire and matched cohorts, except that, in a small number of women who received doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan), risk of mortality was significantly lower for those aged 80 to 84. Chemotherapy appeared to be effective in all ages from 65 through 84 in participants with Stage III colon cancer. For example, in those aged 85 to 89, chemotherapy was significantly associated with lower risk of mortality in the entire cohort (HR = 0.79, 95% CI = 0.67–0.92) and the matched cohort (HR = 0.79, 95% CI = 0.66–0.95).ConclusionThe effectiveness of chemotherapy decreased with age in participants with breast cancer, in whom chemotherapy appears to be effective until age 79 except for the doxorubicin‐cyclophosphamide combination, which was effective in participants aged 80 to 84. In individuals with Stage III colon cancer, chemotherapy appears to be effective to age 89. These findings were consistent with those of randomized clinical trials.
Current Practices and Opportunities in a Resident Clinic Regarding the Care of Older Adults with Multimorbidity
Authors: Schoenborn Nancy L. , Boyd Cynthia M. , McNabney Matthew , Ray Anushree , Cayea Danelle 
Published: July 2015

ObjectivesMultimorbidity (≥2 chronic conditions) affects more than half of all older adults. The American Geriatrics Society developed and published guiding principles for the care of older adults with multimorbidity in 2012. Improved clinician training in caring for older adults with multimorbidity is needed, but it is not clear what opportunities arise within clinical encounters to apply the guiding principles or how clinicians at all stages of training currently practice in this area. This project aimed to characterize current practice and opportunities for improvement in an internal medicine residency clinic regarding the care of older adults with multimorbidity.DesignQualitative content analysis of audio‐recorded clinic visits.Setting and ParticipantsThirty clinic visits between 21 internal medicine residents and 30 of their primary care patients aged 65 and older with two or more chronic conditions were audio‐recorded. Patients' mean age was 73.6, and they had on average 3.7 chronic conditions and took 12.6 medications.MeasurementsTranscripts of the audio‐recorded visit discussions were analyzed using standard techniques of qualitative content analysis to describe the content and frequency of discussions in the clinic visits related to the five guiding principles: patient preferences, interpreting the evidence, prognosis, clinical feasibility, and optimizing therapies.Results and ConclusionsAll visits except one included discussions that were thematically related to at least one guiding principle, suggesting regular opportunities to apply the guiding principles in primary care encounters with internal medicine residents. Discussions related to some guiding principles occurred much more frequently than others. Patients presented a number of opportunities to incorporate the guiding principles that the residents missed, suggesting target areas for future educational interventions.