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Population Pharmacokinetic Pharmacodynamic Modeling of Caffeine Using Visual Analogue Scales

Pharmacology & Pharmacy 2014年第4期5卷 444-454页

作者： rebecca n.burns Ayyappa Chaturvedula David C.Turner Hailing Zhang Chad M.Van Den Berg Center for Pharmacometrics Mercer UniversityAtlantaUSA Department of Pharmaceutical Sciences Mercer UniversityAtlantaUSA Department of Pharmacy Practice Mercer UniversityAtlantaUSA Center for Clinical Research Mercer UniversityAtlantaUSA

Caffeine is a commonly ingested psychoactive substance which affects alertness and cognition. A clinical study was conducted to determine the effect of orally ingested caffeine on visual analogue scale (VAS) responses in healthy, moderate caffeine-consuming volunteers through the use of population pharmacokinetic-pharmacodynamic (PK-PD) modeling. Twelve subjects were recruited for a three-period cross-over study which utilized caffeine containing beverages. Each visit included 8-hour blood plasma and VAS response collection for PK and PD assessment respectively. The VAS used in the study, also called the caffeine analog scale, has been previously validated for caffeine. Population PK-PD modeling was conducted with nOnMEM 7.2. Simultaneous and sequential modeling of PK-PD was attempted. Final model selection was based on parameter estimate precision, diagnostic plots, and visual predictive check (VPC) plots. Results showed that a one-compartment open model with first-order absorption and elimination best described the pharmacokinetics of caffeine. Sequential PK-PD modeling was successful and an effect compartment model with linear slope and baseline parameter best described caffeine pharmacodynamics. Diagnostic plots showed no major bias and VPC plots showed agreement between observations and predictions. The model was able to link VAS responses to caffeine concentration in healthy volunteers and may be useful in clinical trial simulations and design.

关键词： Caffeine Population Pharmacokinetics Population Pharmacodynamics nOnMEM? Visual Analogue Scale

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Manipulation of photosensory and circadian signaling restricts phenotypic plasticity in response to changing environmental conditions in Arabidopsis

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Molecular Plant 2024年第9期17卷 1458-1471页

作者： Martin William Battle Scott Fraser Ewing Cathryn Dickson Joseph Obaje Kristen n.Edgeworth rebecca Bindbeutel Rea LAntoniou-Kourounioti Dmitri A.nusinow Matthew Alan Jones Plant Science Group School of Molecular BiosciencesUniversity of GlasgowGlasgow G128QQUK Danforth Plant Science Center St.LouisMO 63132USA Department of Biological and Biomedical Sciences Washington University in St.LouisSt.LouisMO 63130USA Present address:School of Biological and Environmental Sciences Liverpool John Moores UniversityLiverpool L22QPUK

Plants exploit phenotypic plasticity to adapt their growth and development to prevailing environmental *** of light and temperature signals is aided by the circadian system,which provides a temporal *** plasticity provides a selective and competitive advantage in nature but is obstructive during large-scale,intensive agricultural practices since economically important traits(including vegetative growth and flowering time)can vary widely depending on local environmental *** prevents accurate prediction of harvesting times and produces a variable *** this study,we sought to restrict phenotypic plasticity and circadian regulation by manipulating signaling systems that govern plants'responses to environmental *** modeling of plant growth and develop-ment predicted reduced plant responses to changing environments when circadian and light signaling pathways were *** tested this prediction by utilizing a constitutively active allele of the plant photoreceptor phytochrome B,along with disruption of the circadian systemvia mutation of *** found that these manipulations produced plants that are less responsive to light and temper-ature cues and thus fail to anticipate *** engineered plants have uniform vegetative growth and flowering time,demonstrating how phenotypic plasticity can be limited while maintaining plant *** has significant implications for future agriculture in both open fields and controlled environments.

关键词： circadian developmental plasticity phenotypic plasticity external coincidence light temperature

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Frequency of the C677T Polymorphism of MTHFR, G20210A of Prothrombin and R506Q of Factor V Leiden in Type 2 Diabetics in Abidjan

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Open Journal of Genetics 2024年第1期14卷 13-25页

作者： n’Guessan-Blao rebecca Yapo Vincent Yayo-Ayé Mireille Adjambri Eusèbe Koné-Koné Fatoumata Sawadogo Duni Hematology and General Biology Unit Faculty of Pharmaceutical and Biological Sciences Department of Biological Sciences Felix Houphouet-Boigny University Abidjan Ivory Coast Laboratory of Biology and Medical Research National Institute of Public Health (INSP) Abidjan Ivory Coast Molecular Biology Unit Center for Diagnosis and Research on AIDS and Other Infectious Diseases (CeDReS) Treichville University Hospital (CHU) Abidjan Ivory Coast

In Africa, the prevalence of diabetes is escalating and remains a concern due to the numerous complications it causes. Vascular damage associated with diabetes leads to a prothrombotic state observed in diabetic individuals. Diabetes is a complex and multifactorial disease involving genetic components. With the aim of preventing complications and contributing to an efficient management of diabetes, we investigated genes likely to lead to a risk of thrombosis, in particular the C677T of MTHFR, G20210A of prothrombin, and R506Q of factor V Leiden in type 2 diabetics in Abidjan receiving ambulatory care. A descriptive cross-sectional study was carried out on consenting type 2 diabetic patients. Mutation detection was carried out using the PCR-RFLP method employing restriction enzymes. Hemostasis tests (fibrinogen, D-dimers, fibrin monomers, and von Willebrand factor) were performed using citrate tubes on the Stage? Star Max automated system. Plasminogen activator inhibitor was assayed by ELISA method, and biochemical parameters were determined using the COBAS C311. The study population consisted of 45 diabetic patients, 51.1% of whom presented vascular complications, mainly neuropathy. Disturbances in hemostasis parameters were observed, with 15.5% of patients showing an increase in fibrin monomers. Mutation analysis revealed an absence of factor V mutation (factor V Leiden) and of G20210A mutation of the prothrombin gene. However, 15.6% of subjects had a heterozygous C677T mutation of MTHFR, with 57% of them being anemic. The exploration of biological and genetic factors associated with thrombotic risk is of significant interest in the optimal management of African type 2 diabetics.

关键词： Type 2 Diabetes C677T of MTHFR G20210A Factor V Leiden Thrombosis

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Integration between Genomic and Computational Statistical Surveys for the Screening of SnP Genetic Variants in Inflammatory Bowel Disease (IBD) Pediatric Patients*

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Computational Molecular Bioscience 2024年第3期14卷 146-191页

作者： Dago Dougba noel Koffi n’Guessan Bénédicte Sonia Dagnogo Olefongo Daramcoum Wentoin Alimata Marie-Pierre Mauro Giacomelli Dagnogo Dramane Eboulé Ago Eliane rebecca Yao Saraka Didier Martial Diarrassouba nafan Giovanni Malerba Raffaele Badolato Department of Clinical and Experimental Sciences University of Brescia Brescia Italy Angelo nocivelli Institute of Molecular Medicine Childrens Hospital ASST Spedali Civili Brescia Italy Unit of Biostatistics and Biomathematics & Unit of Bioinformatics Department of Molecular and Translational Medicine University of Brescia Brescia Italy Biological Sciences Training and Research Unit Department of Genetic and Biochemistry Peleforo Gon Coulibaly University Korhogo Cte dIvoire Department of neurosciences Biomedicine and Movement Sciences Section of Biology and Genetics University of Verona Verona Italy Biosciences Training and Research Unit Biology and Health Laboratory Felix Houphouet-Boigny University Abidjan Cte dIvoire

Inflammatory bowel diseases (IBD) are complex multifactorial disorders that include Crohn’s disease (CD) and ulcerative colitis (UC). Considering that IBD is a genetic and multifactorial disease, we screened for the distribution dynamism of IBD pathogenic genetic variants (single nucleotide polymorphisms;SnPs) and risk factors in four (4) IBD pediatric patients, by integrating both clinical exome sequencing and computational statistical approaches, aiming to categorize IBD patients in CD and UC phenotype. To this end, we first aligned genomic read sequences of these IBD patients to hg19 human genome by using bowtie 2 package. next, we performed genetic variant calling analysis in terms of single nucleotide polymorphism (SnP) for genes covered by at least 20 read genomic sequences. Finally, we checked for biological and genomic functions of genes exhibiting statistically significant genetic variant (SnPs) by introducing Fitcon genomic parameter. Findings showed Fitcon parameter as normalizing IBD patient’s population variability, as well as inducing a relative good clustering between IBD patients in terms of CD and UC phenotypes. Genomic analysis revealed a random distribution of risk factors and as well pathogenic SnPs genetic variants in the four IBD patient’s genome, claiming to be involved in: i) Metabolic disorders, ii) Autoimmune deficiencies;iii) Crohn’s disease pathways. Integration of genomic and computational statistical analysis supported a relative genetic variability regarding IBD patient population by processing IBD pathogenic SnP genetic variants as opposite to IBD risk factor variants. Interestingly, findings clearly allowed categorizing IBD patients in CD and UC phenotypes by applying Fitcon parameter in selecting IBD pathogenic genetic variants. Considering as a whole, the study suggested the efficiency of integrating clinical exome sequencing and computational statistical tools as a right approach in discriminating IBD phenotypes as well as improvi

关键词： Inflammatory Bowel Disease (IBD) Crohn Disease (CD) Ulcerative Colitis (UC) Clinical Exome Analysis Computational Statistic SnP Genetic Variants

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An integrative view of the signaling phenotype： Dynamic links between signals, physiology, behavior and social context

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Current Zoology 2014年第6期60卷 739-754页

作者： Maren n. VITOUSEK David M. ZOnAnA rebecca J. SAFRAn Department of neurobiology and Behavior Comell University Ithaca New York 14853 USA Department of Ecology and Evolutionary Biology University of Colorado Boulder Colorado 80309 USA

Signal traits are often linked with the physiological state and behavior of their bearer. Direct examination of the causal links among these variables has provided substantial insight into the information content of signals, and into the costs and benefits of signal expression. Yet recent empirical work suggests that the social context in which signals are developed and displayed can play a major role not only in how signals are received, but also in coordinating and mediating the signaling phenotype itself. Here we review both well-established and emerging evidence for direct feedbacks among an individual＇s physiological state, be- havior, and signal elaboration. We then describe an integrative view of signaling that takes into account the bidirectional rela- tionships among components of phenotype and the social context in which signals are developed and displayed. Integrating dy- namic feedback between context and phenotype within models of the evolution and maintenance of signals may yield insights into how signals evolve, how signaling phenotypes are coordinated and maintained on ecological and evolutionary time scales, and how static signals continue to convey relevant phenotypic information about their bearer through time.

关键词： Behavior Phenotype Physiology Signal trait Social feedback Sexual selection

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Climate drives differences in the germination niche of a globally distributed invasive grass

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Journal of Plant Ecology 2020年第2期13卷 195-203页

作者： rebecca A.Fletcher Kayla M.Varnon Jacob n.Barney Virginia Tech School of Plant and Environmental Sciences675 Old Glade RdBlacksburgVA 24061USA

Aims Exotic invasive species are often exposed to strong selection pressures in their new ranges that can often lead to substantial intraspecific *** differentiation in the timing of life history events in response to climate gradients is thought to be an important mechanism facilitating the range expansion of many invasive *** seed producing plants,the timing of seed germination determines the first environmental conditions experienced by newly emerged germinates,and can have important implications for the successful colonization,establishment and spread of invasive plants—though the role of germination in the success of invasive plants remains poorly *** We assessed the variation in seed germination dynamics among 10 populations of the invasive plant Johnsongrass(Sorghum halepense)across its north American distribution,capturing both a temperature and precipitation gradient,and whether that variation is associated with home *** were exposed to a wide range of temperatures(11–48℃)and two water availability *** Findings We found that Johnsongrass seeds germinated across a wide range of temperatures,but there was substantial variation among populations in the proportion of seeds that germinated in response to both temperature and water *** indicates that as Johnsongrass expanded its range from warmer climates into cooler climates,there was a concurrent shift in the germination temperature niche to cooler *** results suggest that the germination of Johnsongrass seeds has adapted to home climate allowing this invader to maximize germination throughout its range,and that this may be an important contributing factor to its invasion into new environments.

关键词： adaptation among-population variation Johnsongrass Sorghum halepense temperature water availability

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Ecological and evolutionary connections between morphology, physiology, and behavior

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Current Zoology 2014年第6期60卷 736-738页

作者： rebecca J. SAFRAn Maren n. VITOUSEK Guest Editors Department of Ecology and Evolutionary Biology University of Colorado Boulder Colorado 80309 USA Department of neurobiology and Behavior Comell University Ithaca New York 14853 USA

1 Introduction Phenotype variation within populations both provides the raw material for and is the product of evolutionary change. An individual＇s phenotype, defined as the amalgamation of morphology, physiology, and behavior, is highly complex. It has been common to try to isolate each of these aspects of phenotype rather than directly examine their integration. For example, despite the demonstrated importance of single aspects of phenotype for acquiring mates it is well known that signal traits are not evaluated in isolation, but rather in conjunction with associated behaviors, and sometimes with other signal traits （Moiler and Pomiankowski, 1993; Candolin, 2003;

关键词：形态学生理学行为进化表型变异连接生态信号特性

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Intracranial pressure is elevated at 24h post-stroke inmice

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neuroprotection 2024年第1期2卷 60-64页

作者： Kirby E.Warren rebecca J.Hood Fredrick R.Walker neil J.Spratt School of Biomedical Sciences and Pharmacy University of NewcastleCallaghanAustralia Hunter Medical Research Institute NewLambton HeightsAustralia School of Biomedicine Discipline of Anatomy and PathologyFaculty of Health and Medical SciencesThe University of AdelaideAdelaideAustralia Department of neurology John Hunter HospitalNewLambton HeightsAustralia

Background:It has long been assumed that post-stroke intracranial pressure(ICP)elevation occurs because of large infarct and edema ***,we have repeatedly shown IcP elevation at 24 h post-stroke in the presence of little to no edema in *** processes are often conserved across species and types of ***,we aimed to determine if an ICP rise occurs at 24 h post-stroke in the presence of small infarct and edema volumes in ***:Mice were randomized by random number table to either photothrombotic stroke or sham surgery(n=15).Epidural ICP was recorded using a fiber optic catheter at 1 h post-stroke(baseline)and between 23 and ***:ICP was significantly higher at 24 h compared to baseline in stroke animals(n=6;10.71±6.45mmHg vs.3.74±2.20mmHg,respec-tively;p=0.03).ICP at 24 h was also significantly higher in stroke mice compared to sham(n=6;3.45±1.43mmHg;p=0.02).There was no change in ICP in sham mice(p=0.9).Edema volumes in stroke animals were small(0.04±0.04 mm3)and unlikely to have caused significant ICP ***:This study provides evidence of an edema-independent ICP elevation following small ischemic stroke in *** occurrence of this rise supports our findings in other species and suggests it is caused by a previously undescribed mechanism.

关键词： cerebraledema intracranial pressure ischemic stroke

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Mycorrhizal Symbioses of Cotton Grown on Sodic Soils:A Review from an Australian Perspective

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Pedosphere 2017年第6期27卷 1015-1026页

作者： Samieh ESKAnDARI Christopher n.GUPPY Oliver G.G.KnOX David BACKHOUSE rebecca E.HALInG School of Environmental and Rural Science University of New EnglandArmidale NSW 2351(Australia) CSIRO Agriculture Canberra ACT 2601(Australia)

The majority of terrestrial plants form some type of mycorrhizal *** established symbiosis therefore exists in most commercially important crops, which includes *** mycorrhizal fungus(AMF) can colonise 50%–90% of cotton root length under field and controlled *** improves growth and nutrient uptake(especially phosphorus) of cotton,particularly at the early growth *** symbioses help plants to counter the stresses imposed by physical and chemical soil constraints; however, adverse environmental conditions may restrict the mycorrhizal associations and consequently may reduce nutrient uptake and impair plant *** Australia, cotton is mainly grown on sodic soils that contain more than 6% of the total cations as exchangeable *** levels of sodium in the soil create adverse physical and chemical soil conditions that may negatively affect mycorrhizal symbioses of *** review discusses the cotton mycorrhizal colonisation, plant growth, and disease protection effects, potential negative effects of physical and chemical properties of sodic soils, and influences of some agronomic management *** addition, the research gaps were identified and some practical applications of the research outcomes were suggested.

关键词： agronomic management axbuscular mycorrhizal fungus (AMF) disease protection exchangeable sodium pathogen,plant growth soil property

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Impaired cellulose decomposition in a headwater stream receiving subsurface agricultural drainage

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Ecological Processes 2022年第1期11卷 845-861页

作者： rebecca Poisson Adam G.Yates Department of Geography Western UniversityLondonONCanada Department of Biology University of WaterlooWaterloo University200 University Avenue WestWaterlooON N2L 3G1Canada

Background:Agricultural development of former wetlands has resulted in many headwater streams being sourced by subsurface agricultural drainage *** drainage inputs can significantly influence stream environmental conditions,such as temperature,hydrology,and water chemistry,that drive ecological ***,ecological assessments of subsurface drainage impacts are *** assessed the impact of an agricultural drainage system on cellulose decomposition and benthic respiration using a paired stream study in a headwater branch of nissouri Creek,in Ontario,*** first order segments sourced by a spring-fed marsh and a cropped field with subsurface drainage,as well as the adjoining trunk segment,were sampled over a year using the cotton strip assay to measure cellulose decomposition and benthic ***:Assessments of cellulose decomposition revealed a one-third reduction in the drainage-sourced segment compared to marsh-sourced *** segment differences in cellulose decomposition were associated with reduced summer temperatures in the drainage-sourced *** of stream cooling from the drainage-sourced segment were transmitted downstream as cellulose decomposition was slower than expected throughout the drainage-sourced segment and for several hundred meters down the adjoining trunk *** respiration only differed between the drainage-and marsh-sourced segments in spring,when stream temperatures were ***:Our findings suggest there may be a widespread reduction in cellulose decomposition in streams across similar agricultural regions where subsurface drainage is ***,cooling of streams receiving significant amounts of water inputs from subsurface drainage systems may impart increased resiliency to future climate warming.

关键词： Stream Agriculture Cotton strip assay Seasonality Organic matter breakdown Benthic respiration

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