bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allosteric effects of erythromycin pretreatment on thioridazine block of hERG potassium channels
Authors: Crumb W J 
Published: January 2014

Background and PurposeThe prevalence of concurrent use of two or more drugs that block human ether‐a‐go‐go‐related gene product (hERG) K+ channels is not uncommon, but is not well characterized. This study defined the effects of concurrent exposure of two hERG‐blocking drugs on hERG current amplitude. Experiments were conducted to determine if concomitant exposure to two potent pore hERG blockers, thioridazine and terfenadine and a weak hERG blocker, erythromycin, would result in an additive, synergistic or inhibitory effect.Experimental ApproachhERG currents from stably transfected HEK cells were measured using the whole‐cell variant of the patch‐clamp method at physiological temperatures. Concentration–response relationships for thioridazine or terfenadine were obtained with cells pre‐exposed to erythromycin.Key ResultsPre‐exposure of cells to erythromycin resulted in an approximately 14–22‐fold rightward shift in the hERG concentration–response curve for thioridazine and terfenadine respectively. This reduction in affinity was not the result of a change in the voltage‐dependent characteristics of the channel. Results suggest an external binding site for erythromycin.Conclusions and ImplicationsPretreatment with erythromycin induced an approximately 14–22‐fold reduction in hERG affinity for pore‐binding drugs at concentrations of erythromycin, which by themselves only block hERG by 10% or less. These results suggest distinct, allosterically linked binding sites on opposite sides of the hERG channel. Occupancy of the external site by erythromycin reduces the affinity of the pore binding site. Furthermore, these results suggest that co‐administration of erythromycin may provide some reduction in cardiac liability of potent hERG‐blocking drugs.
In vivo effects of the pure aryl hydrocarbon receptor antagonist GNF‐351 after oral administration are limited to the gastrointestinal tract
Authors: Fang Zhong‐Ze , Krausz Kristopher W , Nagaoka Kenjiro , Tanaka Naoki , Gowda Krishne , Amin Shantu G , Perdew Gary H , Gonzalez Frank J 
Published: January 2014

Background and PurposeGNF‐351 is a potent aryl hydrocarbon receptor (AHR) antagonist that inhibits dioxin response element‐dependent and independent activities. Here, the absorption, metabolism and in vivo AHR antagonist activity of GNF‐351 were investigated.Experimental ApproachLC‐MS metabolomics was used to analyse GNF‐351 metabolism in vitro and in vivo. Recombinant drug‐metabolizing enzymes were employed to determine the enzymes involved in GNF‐351 metabolism. Analysis of target AHR genes was performed to investigate the inhibitory effects of GNF‐351 towards AHR activation.Key ResultsSeveral phase I metabolites were generated after GNF‐351 was incubated with microsomes from human or mouse liver and intestine, including two oxidized GNF‐351 and one tri‐demethylated GNF‐351. Poor absorption from the intestine resulted in no detectable levels of GNF‐351 in mouse serum (0–6 h) and urine (24 h) and almost all GNF‐351 was found in the faeces after 24 h. Analysis of faeces further revealed all the in vitro phase I metabolites. Novel metabolites were detected, including one di‐oxidized GNF‐351, two oxidized and tri‐demethylated GNF‐351, one dehydrogenated product of oxidized GNF‐351, and one sulfation product of di‐oxidized GNF‐351. Cytochromes P450 were demonstrated to be the major enzymes involved in metabolism of GNF‐351. After oral administration to mice, GNF‐351 readily inhibited β‐naphthoflavone‐induced AHR activation in ileum and colon, but not that in the liver.Conclusion and ImplicationsWhile poor absorption and extensive metabolism after oral administration limited the in vivo effects of the pure AHR antagonist GNF‐351 in liver, it could be used to inhibit AHR activation in intestine and colon.
Characterizing the Width of Amphibian Movements During Postbreeding Migration
Authors: COSTER STEPHANIE S. , VEYSEY POWELL JESSICA S. , BABBITT KIMBERLY J. 
Published: January 2014

AbstractHabitat linkages can help maintain connectivity of animal populations in developed landscapes. However, the lack of empirical data on the width of lateral movements (i.e., the zigzagging of individuals as they move from one point to point another) makes determining the width of such linkages challenging. We used radiotracking data from wood frogs (Lithobates sylvaticus) and spotted salamanders (Ambystoma maculatum) in a managed forest in Maine (U.S.A.) to characterize movement patterns of populations and thus inform planning for the width of wildlife corridors. For each individual, we calculated the polar coordinates of all locations, estimated the vector sum of the polar coordinates, and measured the distance from each location to the vector sum. By fitting a Gaussian distribution over a histogram of these distances, we created a population‐level probability density function and estimated the 50th and 95th percentiles to determine the width of lateral movement as individuals progressed from the pond to upland habitat. For spotted salamanders 50% of lateral movements were ≤13 m wide and 95% of movements were ≤39 m wide. For wood frogs, 50% of lateral movements were ≤17 m wide and 95% of movements were ≤ 51 m wide. For both species, those individuals that traveled the farthest from the pond also displayed the greatest lateral movement. Our results serve as a foundation for spatially explicit conservation planning for pond‐breeding amphibians in areas undergoing development. Our technique can also be applied to movement data from other taxa to aid in designing habitat linkages.Caracterización de la Amplitud de Movimiento de Anfibios durante la Migración Pos‐Reproducción
Septic sialoadenitis in equids: A retrospective study of 18 cases (1998–2010)
Authors: Kilcoyne I. , Watson J. L. , Spier S. J. , Whitcomb M. B. , Vaughan B. 
Published: January 2014

SummaryReason for performing studySeptic sialoadenitis, although uncommonly reported in equids, is a significant cause of pain, inappetence, dysphagia and discomfort. There are currently few reported cases possibly as a result of its infrequent occurrence.ObjectivesTo review cases presenting with sialoadenitis and describe the presenting complaints, results of diagnostic tests, treatment and outcome.Study designRetrospective case series.MethodsRecords were reviewed for equids presenting to the UC Davis William R. Pritchard Veterinary Medical Teaching Hospital between 1998 and 2010 for salivary gland swelling. Equids were included if a diagnosis of septic sialoadenitis was made based on a combination of oral examination and/or ultrasonographic findings and/or microbial culture. Data collected included age, breed, presenting complaints, diagnostic results, treatment and outcome.ResultsEighteen equids were diagnosed with septic sialoadenitis affecting the parotid gland (11) or the mandibular salivary gland (7). Ultrasound was useful to differentiate whether the mandibular or parotid salivary gland was involved. Affected equids ranged in age from 4 to 30 years (mean 17.7 years). Fourteen of 15 (93.3%) equids that underwent a complete oral examination had dental or other oral abnormalities. Six of 18 cases had evidence of sialolithiasis. Culture of the infected salivary gland or secretions was performed in 9 equids and all yielded growth of Fusobacterium sp. along with other aerobic and anaerobic bacteria. Infection resolved in 15/18 cases (83.3%) and 2/18 (11.1%) were subjected to euthanasia.ConclusionsDental disease and sialolith formation may play important roles in the development of septic sialoadenitis in equids. Anaerobic infection should be assumed in all cases and affected horses should be treated for this until culture and sensitivity results are available. Prognosis is favourable (83.3%) with appropriate treatment.
Do Good Fences Make Good Neighbors? The Cross Border Impact of Casino Entrance
Authors: Hicks Michael J. 
Published: January 2014

AbstractThis study estimates the impact of casino entrance in adjacent counties on aggregate and selected subsector incomes on counties adjacent in Indiana from 1990 to 2008. Employing a spatial econometric model and an approach that combines pre‐casino entrance forecasts and actual income changes, this study finds very modest increases in income growth in casino counties in the econometric model but adjacent county income declines which are economically irrelevant. The forecast approach mirrors, with less precision, this finding. These findings suggest that welfare effects of casinos are more geographically distributed than the literature has yet reported primarily because of the redistribution of retail trade.
Facilitators to Promoting Health in Schools: Is School Health Climate the Key?
Authors: Lucarelli Jennifer F. , Alaimo Katherine , Mang Ellen , Martin Caroline , Miles Richard , Bailey Deborah , Kelleher Deanne K. , Drzal Nicholas B. , Liu Hui 
Published: January 2014

ABSTRACTBACKGROUNDSchools can promote healthy eating in adolescents. This study used a qualitative approach to examine barriers and facilitators to healthy eating in schools.METHODSCase studies were conducted with 8 low‐income Michigan middle schools. Interviews were conducted with 1 administrator, the food service director, and 1 member of the coordinated school health team at each school.RESULTSBarriers included budgetary constraints leading to low prioritization of health initiatives; availability of unhealthy competitive foods; and perceptions that students would not eat healthy foods. Schools had made improvements to foods and increased nutrition education. Support from administrators, teamwork among staff, and acknowledging student preferences facilitated positive changes. Schools with a key set of characteristics, (presence of a coordinated school health team, nutrition policies, and a school health champion) made more improvements.CONCLUSIONSThe set of key characteristics identified in successful schools may represent a school's health climate. While models of school climate have been utilized in the educational field in relation to academic outcomes, a health‐specific model of school climate would be useful in guiding school health practitioners and researchers and may improve the effectiveness of interventions aimed at improving student dietary intake and other health behaviors.
Mental Health Service Use Among High School Students Exposed to Interpersonal Violence
Authors: Green Jennifer Greif , Johnson Renee M. , Dunn Erin C. , Lindsey Michael , Xuan Ziming , Zaslavsky Alan M. 
Published: January 2014

ABSTRACTBACKGROUNDViolence‐exposed youth rarely receive mental health services, even though exposure increases risk for academic and psychosocial problems. This study examines the association between violence exposure and mental health service contact. The 4 forms of violence exposure were peer, family, sexual, and witnessing.METHODSData are from 1534 Boston public high school students who participated in a 2008 self‐report survey of violence exposure and its correlates. Multivariate logistic regressions estimated associations between each form of violence with service contact, then examined whether associations persisted when controlling for suicidality and self‐injurious behaviors.RESULTSIn unadjusted models, violence‐exposed students more often reported service contact than their peers. However, in multivariate models, only exposure to family (odds ratio [OR] = 1.69, 95% confidence interval [CI] = 1.23‐2.31) and sexual violence (OR = 2.34, 95% CI = 1.29‐4.20) were associated with service contact. Associations attenuated when controlling for suicidality and self‐injurious behaviors, indicating they were largely explained by self‐harm. Sexual violence alone remained associated with mental health service contact in fully adjusted models, but only for girls (OR=3.32, 95% CI=1.30‐8.45), suggesting sex‐specific pathways.CONCLUSIONSAssociations between adolescent violence exposure and mental health service contact vary by forms of exposure. Outreach to a broader set of exposed youth may reduce the impact of violence and its consequences for vulnerable students.
Weight Status Misperception as Related to Selected Health Risk Behaviors Among Middle School Students
Authors: Martin Brian C. , Dalton William T. , Williams Stacey L. , Slawson Deborah L. , Dunn Michael S. , Johns‐Wommack Rebecca 
Published: January 2014

ABSTRACTBACKGROUNDWeight misperception has been documented among children although the impact on health risk behaviors is less understood, particularly among middle school students. The goals of this study were to describe sociodemographic differences in actual and perceived weight, correspondence between actual and perceived weight, and weight‐related health risk behaviors, as well as to examine weight misperception and interactions with sociodemographic variables in explaining weight‐related health risk behaviors.METHODSParticipants were recruited at 11 public school districts participating in the Tennessee Coordinated School Health (CSH) pilot program. A total of 10,273 middle school students completed the Centers for Disease Control and Prevention's Youth Risk Behavior Survey administered by teachers in the school setting.RESULTSFindings revealed sociodemographic differences in actual and perceived weight as well as weight misperception. Although overestimating one's weight was significantly related to greater likelihood of weight‐related health risk behaviors, significant interactions showed this relationship to be especially pronounced in females. Additional distinctions based on sociodemographic variables are indicated.CONCLUSIONSResults highlight the importance of screening for health risk behaviors including weight misperception among middle school students. The CSH program offers an opportunity to understand health risk behaviors among students while also informing and evaluating methods for intervention.
Comparison of Media Literacy and Usual Education to Prevent Tobacco Use: A Cluster‐Randomized Trial
Authors: Primack Brian A. , Douglas Erika L. , Land Stephanie R. , Miller Elizabeth , Fine Michael J. 
Published: January 2014

ABSTRACTBACKGROUNDMedia literacy programs have shown potential for reduction of adolescent tobacco use. We aimed to determine if an anti‐smoking media literacy curriculum improves students' media literacy and affects factors related to adolescent smoking.METHODSWe recruited 1170 9th‐grade students from 64 classrooms in 3 public urban high schools. Students were randomized by classroom to a media literacy curriculum versus a standard educational program. In an intent‐to‐treat analysis, we used multilevel modeling to determine if changes in study outcomes were associated with the curricular intervention, controlling for baseline student covariates and the clustering of students within classrooms.RESULTSAmong participants, mean age was 14.5 years and 51% were male, with no significant differences in baseline characteristics between groups. Smoking media literacy changed more among intervention participants compared with control participants (0.24 vs. 0.08, p < .001). Compared with controls, intervention students exhibited a greater reduction in the perceived prevalence of smoking (−14.0% vs. −4.6%, p < .001). Among those initially susceptible to smoking, intervention participants more commonly reverted to being nonsusceptible post‐intervention (24% vs. 16%, p = .08).CONCLUSIONSA school‐based media literacy curriculum is more effective than a standard educational program in teaching media literacy and improving perceptions of the true prevalence of smoking among adolescents.
The Optimal Structure for Public Debt
Authors: Kuhle Wolfgang 
Published: January 2014

AbstractWe study risk‐sharing through public debt in a two‐generations‐overlapping model. If bonds and wage‐indexed social security service a given initial obligation, there exists a set of Pareto‐efficient debt structures. This set is characterized by conflicting interests of current and yet unborn cohorts over the factor‐price risk allocation. If both size and composition of the debt are choice variables, these conflicting interests can be reconciled. Changes in the debt's composition reallocate factor‐price risks, while changes in its size reallocate resources. This separation of risk‐sharing and crowding‐out narrows the set of efficient debt structures until only one remains.
Knowledge with and Without Belief
Authors: Veber Michael 
Published: January 2014

AbstractThis article argues for the thesis that the distinction between propositional and doxastic justification should be extended to knowledge. A consequence of this thesis is that there is a type of knowledge that requires belief and a type that does not. A familiar example strikingly similar to the sort of example used to introduce the propositional/doxastic justification makes a prima facie case. Additional theoretical advantages are revealed when the distinction is applied within the context of some recent epistemological debates. These include debates over the knowledge account of assertion, testimonial knowledge, self‐deception, and the question of whether knowledge can be essentially based on falsehood. It is contended that the sort of distinction offered here provides a way to settle these debates and, at the same time, acknowledge what is correct in the opposing positions.
The HAMP signal‐conversion domain: static two‐state or dynamic three‐state?
Authors: Stewart Valley 
Published: January 2014

SummaryThe 50‐residue HAMP domain converts input signal into output response in a variety of transmembrane signal transduction proteins, including methyl‐accepting chemotaxis proteins and histidine kinases. HAMP domains are present in many other contexts as well. Despite focused study over the past decade, the question remains: How does this small domain play such a large role for so many different proteins? Analysis of structural models for the Afl1503 and Aer2 HAMP domains has generated hypotheses in which the HAMP domain assumes either of two discrete forms that generate opposing signal output. In contrast, genetic analysis of the HAMP domain from the Tsr methyl‐accepting chemotaxis protein resulted in a distinct hypothesis, the biphasic dynamic bundle. In this hypothesis, signalling involves differential packing stabilities of the HAMP domain four‐helix bundle, marked by at least three distinct states. Here I summarize and compare these hypotheses in the context of a deletion analysis that further explores the biphasic dynamic bundle hypothesis.
Tracking of chromosome dynamics in live Streptococcus pneumoniae reveals that transcription promotes chromosome segregation
Authors: Kjos Morten , Veening Jan‐Willem 
Published: January 2014

SummaryChromosome segregation is an essential part of the bacterial cell cycle but is poorly characterized in oval‐shaped streptococci. Using time‐lapse fluorescence microscopy and total internal reflection fluorescence microscopy, we have tracked the dynamics of chromosome segregation in live cells of the human pathogen Streptococcus pneumoniae. Our observations show that the chromosome segregation process last for two‐thirds of the total cell cycle; the origin region segregates rapidly in the early stages of the cell cycle while nucleoid segregation finishes just before cell division. Previously we have demonstrated that the DNA‐binding protein ParB and the condensin SMC promote efficient chromosome segregation, likely by an active mechanism. We now show that in the absence of SMC, cell division can occur over the unsegregated chromosomes. However, neither smc nor parB are essential in S. pneumoniae, suggesting the importance of additional mechanisms. Here we have identified the process of transcription as one of these mechanisms important for chromosome segregation in S. pneumoniae. Transcription inhibitors rifampicin and streptolydigin as well as mutants affected in transcription elongation cause chromosome segregation defects. Together, our results highlight the importance of passive (or indirect) processes such as transcription for chromosome segregation in oval‐shaped bacteria.
Assessments of genetic diversity and anthracnose disease response among Zimbabwe sorghum germplasm
Authors: Cuevas Hugo E. , Prom Louis K. , Erpelding John E. , Brotons Veronica 
Published: January 2014

AbstractThe USDA‐ARS National Plant Germplasm System maintains a Zimbabwe sorghum collection of 1235 accessions from different provinces. This germplasm has not been extensively employed in US breeding programmes due to the lack of phenotypic and genetic characterization. Therefore, 68 accessions from Zimbabwe were phenotyped, and evaluated for their anthracnose response for two consecutive years, and genetically characterized with 21 simple sequence repeat markers. Phenotypic analysis showed significant differences among accessions with plant height and panicle length being the most variable traits. Likewise, 25 accessions were anthracnose resistant, nine showed variable responses and 34 were susceptible. Genetic analysis identified 174 alleles with an average of 8.3 alleles and 11.8 genotypes per locus and a polymorphic information content of 0.60. These results reflect a moderate genetically diverse germplasm. Neighbour‐joining clustering analysis revealed that the majority of anthracnose‐resistant accessions showed high genetic relatedness; therefore, this germplasm might represent one to six new sources of resistances. Results presented herein show that the Zimbabwe collection contains valuable germplasm for breeding programmes and is an important source of anthracnose resistance.
The incidence and body site of skin cancers in the population groups of South Africa
Authors: Norval Mary , Kellett Patricia , Wright Caradee Yael 
Published: January 2014

SummaryBackground/PurposeData regarding basal cell carcinoma (BCC), squamous cell carcinoma of the skin (SSCC) and cutaneous melanoma (CM) in multiracial populations are sparse. Here the incidence and body site of these tumours in the South African population in 2000–2004 were analysed.MethodsAnnual age‐standardized incidences and body sites of BCC, SSCC and CM in black, coloured, Asian and white groups were obtained from histological confirmed cases, reported to the National Cancer Registry.ResultsHighest annual incidences of BCC, SSCC and CM occurred in the white group, followed by coloured, then Asian and then black. BCCs and SSCCs were about twice as common in males than females. CM was the least frequent skin tumour, and BCC the most frequent, except in black people. The head was the commonest body site for SSCC and BCC in all groups and both sexes, whereas the lower limb was the predominant site for CM in black people. Mean age at diagnosis was generally mid‐50s for CM, and mid‐60s for BCC and SSCC.ConclusionsIn South Africa, differences in reported incidence rates and body sites of skin tumours by population group and sex occur. Host characteristics, particularly skin phototype, and personal behaviour are likely to affect the risk of these cancers.