bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioluminescence Resonance Energy Transfer (BRET)‐Based Synthetic Sensor Platform for Drug Discovery
Authors: Woo Jongchan , Hong Jason , Dinesh‐Kumar Savithramma P.
Published: April 2017

Bioluminescence resonance energy transfer (BRET) is a technique that analyzes protein‐protein interactions (PPIs). The unique feature of BRET delineates that the resonance energy is generated by the resonance energy donor, Renilla luciferase by the oxidative decarboxylation of coelenterazine substrate. BRET is superior to FRET where issues such as autofluorescence, photobleaching, and light scattering can occur. Recently, BRET has been applied to design synthetic biosensors for monitoring autophagy in vivo and in vitro. Here, we report the methods for constructing a biosensor of human HsLC3a as a probe for autophagy biogenesis and the optimization of the intramolecular BRET assay that allows for high‐throughput screening of chemical modulators of autophagy. User‐friendly working interface with the BRET‐based synthetic sensor of HsLC3a makes drug discovery easy and amenable for high‐throughput. The BRET protocol described here could be easily applicable to generate other biosensors for monitoring PPIs by measurement of intermolecular BRET. © 2017 by John Wiley & Sons, Inc.
Coxibs, Traditional NSAIDs, and Cardiovascular Safety Post‐PRECISION: What We Thought We Knew Then and What We Think We Know Now
Authors: Patrono C , Baigent C
Published: April 2017

The aim of the present review is to analyze how thinking about the cardiovascular safety of nonsteroidal antiinflammatory drugs has evolved during the past two decades, and discuss to what extent the additional information from the Prospective Randomized Evaluation of Celecoxib Integrated Safety Versus Ibuprofen or Naproxen study may alter our current mechanistic understanding and/or clinical practice.
Genetic Polymorphisms in Organic Cation Transporter 1 Attenuates Hepatic Metformin Exposure in Humans
Authors: Sundelin EIO , Gormsen LC , Jensen JB , Vendelbo MH , Jakobsen S , Munk OL , Christensen MMH , Brøsen K , Frøkiær J , Jessen N
Published: April 2017

Metformin has been used successfully to treat type 2 diabetes for decades. However, the efficacy of the drug varies considerably from patient to patient and this may in part be due to its pharmacokinetic properties. The aim of this study was to examine if common polymorphisms in SLC22A1, encoding the transporter protein OCT1, affect the hepatic distribution of metformin in humans. We performed noninvasive 11C‐metformin positron emission tomography (PET)/computed tomography (CT) to determine hepatic exposure in 12 subjects genotyped for variants in SLC22A1. Hepatic distribution of metformin was significantly reduced after oral intake in carriers of M420del and R61C variants in SLC22A1 without being associated with changes in circulating levels of metformin. Our data show that genetic polymorphisms in transporter proteins cause variation in hepatic exposure to metformin, and it demonstrates the application of novel imaging techniques to investigate pharmacogenetic properties in humans.
Quantitative analysis of cell proliferation by a dye dilution assay: Application to cell lines and cocultures
Authors: Chung Soobin , Kim Seol‐Hee , Seo Yuri , Kim Sook‐Kyung , Lee Ji Youn
Published: April 2017

Cell proliferation represents one of the most fundamental processes in biological systems, thus the quantitative analysis of cell proliferation is important in many biological applications such as drug screening, production of biologics, and assessment of cytotoxicity. Conventional proliferation assays mainly quantify cell number based on a calibration curve of a homogeneous cell population, and therefore are not applicable for the analysis of cocultured cells. Moreover, these assays measure cell proliferation indirectly, based on cellular metabolic activity or DNA content. To overcome these shortcomings, a dye dilution assay employing fluorescent cell tracking dyes that are retained within cells was applied and was diluted proportionally by subsequent cell divisions. Here, it was demonstrated that this assay could be implemented to quantitatively analyze the cell proliferation of different types of cell lines, and to concurrently analyze the proliferation of two types of cell lines in coculture by utilizing cell tracking dyes with different spectral characteristics. The mean division time estimated by the dye dilution assay is compared with the population doubling time obtained from conventional methods and values from literature. Additionally, dye transfer between cocultured cells was investigated and it was found that it is a characteristic of the cells rather than a characteristic of the dye. It was suggested that this method can be easily combined with other flow cytometric analyses of cellular properties, providing valuable information on cell status under diverse conditions. © 2017 International Society for Advancement of Cytometry
Examining the interplay of climate and low amplitude sea‐level change on the distribution and volume of massive dolomitization: Zebbag Formation, Cretaceous, Southern Tunisia
Authors: Newport Richard , Hollis Cathy , Bodin Stéphane , Redfern Jonathan
Published: April 2017

During the Cretaceous, a humid global climate, calcitic seas, high relative sea‐level and low amplitude changes in relative sea‐level largely prevented large‐scale dolomitization in many carbonate successions. However, the well‐exposed shallow‐water carbonate sediments of the Upper Albian–Lower Turonian Zebbag Formation on the Jeffara Escarpment, southern Tunisia, are pervasively dolomitized. This study considers why dolomitization was so widespread in this region during a period of Earth history when platform‐scale dolomitization is rare. Marine conditions were established in the Upper Albian, evidenced by stacked upward‐shallowing packages of shallow subtidal to peritidal carbonate sediments in the basal Rhadouane Member. A gradual increase in the volume of subtidal sediments in the Cenomanian Kerker Member, culminated in deposition of laterally extensive marls, during maximum flooding of the platform in the Lower Turonian. The overlying Gattar Member was then deposited in shallower water as relative sea‐level fell. The entire Zebbag Formation is pervasively replaced by stratabound, fabric‐retentive, dolomite, except within the marl at the top of the Kerker Member, which is only partially dolomitized. Petrographic textures indicate dolomitization largely post‐dated marine cementation and platform emergence but pre‐dated chemical compaction. Slightly more positive oxygen isotope signatures, slightly elevated concentrations of Sr and a near‐absence of evaporites are consistent with dolomitization by reflux of mesohaline sea water. An upward‐decrease in major element concentrations and higher 87Sr/86Sr compared to Upper Cretaceous sea water suggest that basal, Albian siliciclastic beds acted as aquifers facilitating dolomitization by fluxing fluids offshore. Dolomitization is interpreted to have resulted from multiple fluxes of sea water over periods of 0·5 to 2·5 Ma. The unusually high volume of dolostone for a platform of this age most probably reflects deposition within an arid climate belt, where an efficient reflux system was facilitated by basal, permeable siliciclastic strata.
Behavioral responses to encounter of fishing boats in wandering albatrosses
Authors: Collet Julien , Patrick Samantha C. , Weimerskirch Henri
Published: April 2017

Animals are attracted to human food subsidies worldwide. The behavioral response of individuals to these resources is rarely described in detail, beyond chances of encounters. Seabirds for instance scavenge in large numbers at fishing boats, triggering crucial conservation issues, but how the response to boats varies across encounters is poorly known. Here we examine the behavioral response of wandering albatrosses (Diomedea exulans), equipped with GPS tags, to longline fishing boats operating near their colony for which we had access to vessel monitoring system data. We distinguish between encounters (flying within 30 km of a boat) and attendance behavior (sitting on the sea within 3 km of a boat), and examine factors affecting each. In particular, we test hypotheses that the response to encountered boats should vary with sex and age in this long‐lived dimorphic species. Among the 60% trips that encountered boats at least once, 80% of them contained attendance (but attendance followed only 60% of each single encounter). Birds were more attracted and remained attending longer when boats were hauling lines, despite the measures enforced by this fleet to limit food availability during operations. Sex and age of birds had low influence on the response to boats, except the year when fewer boats came fishing in the area, and younger birds were attending further from boats compared to older birds. Net mass gain of birds was similar across sex and not affected by time spent attending boats. Our results indicate albatrosses extensively attend this fishery, with no clear advantages, questioning impacts on foraging time budgets. Factors responsible for sex foraging segregation at larger scale seem not to operate at this fleet near the colony and are not consistent with predictions of optimal foraging theory on potential individual dominance asymmetries. This approach complements studies of large‐scale overlap of animals with human subsidies.
Wolf in sheep's clothing: Model misspecification undermines tests of the neutral theory for life histories
Authors: Authier Matthieu , Aubry Lise M. , Cam Emmanuelle
Published: April 2017

Understanding the processes behind change in reproductive state along life‐history trajectories is a salient research program in evolutionary ecology. Two processes, state dependence and heterogeneity, can drive the dynamics of change among states. Both processes can operate simultaneously, begging the difficult question of how to tease them apart in practice. The Neutral Theory for Life Histories (NTLH) holds that the bulk of variations in life‐history trajectories is due to state dependence and is hence neutral: Once previous (breeding) state is taken into account, variations are mostly random. Lifetime reproductive success (LRS), the number of descendants produced over an individual's reproductive life span, has been used to infer support for NTLH in natura. Support stemmed from accurate prediction of the population‐level distribution of LRS with parameters estimated from a state dependence model. We show with Monte Carlo simulations that the current reliance of NTLH on LRS prediction in a null hypothesis framework easily leads to selecting a misspecified model, biased estimates and flawed inferences. Support for the NTLH can be spurious because of a systematic positive bias in estimated state dependence when heterogeneity is present in the data but ignored in the analysis. This bias can lead to spurious positive covariance between fitness components when there is in fact an underlying trade‐off. Furthermore, neutrality implied by NTLH needs a clarification because of a probable disjunction between its common understanding by evolutionary ecologists and its translation into statistical models of life‐history trajectories. Irrespective of what neutrality entails, testing hypotheses about the dynamics of change among states in life histories requires a multimodel framework because state dependence and heterogeneity can easily be mistaken for each other.
Increasing copper alters cellular elemental composition (Mo and P) of marine diatom
Authors: Wang Deli , Xia Weiwei , Kumar K. Suresh , Gao Kunshan
Published: April 2017

The elemental composition (surface adsorbed and internalized fraction of Cu, Mo and P) in marine phytoplankton was first examined in cultures of the diatom Phaeodactylum tricornutum which were exposed to various levels of Cu concentrations ranging from 0.25 to 16 μmol/L with equivalent free [Cu2+] concentrations of 0.4–26 nmol/L. We observed an acceleration of algal growth rates (20–40%) with increasing ambient Cu levels, as well as slightly increased levels of internalized Cu in cells (2–13 × 10−18 mol/cell) although cellular Cu mostly accumulated onto the cell surface (>50% of the total: intracellular + surface adsorbed). In particular, we documented for the first time that the elemental composition (Mo and P) in algal cells varies dynamically in response to increased Cu levels: (1) Cellular P, predominantly in the intracellular compartment (>95%), shows with a net consumption as indicated by a gradual decrease with increasing [Cu2+] (120→50 × 10−15 mol P/cell) probably due to the fact that P, a backbone bioelement, is largely required in forming biological compartments such as cell membranes; and (2) cellular Mo, predominantly encountered in the intracellular compartment, showed up to tenfold increase in concentration in the cultures exposed to Cu, with a peak accumulation of 1.1 × 10−18 mol Mo/cell occurring in the culture exposed to [Cu2+] at 3.7 nmol/L. Such a net cellular Mo accumulation suggests that Mo might be specifically required in biological processes, probably playing a counteracting role against Cu.
A multispecies dependent double‐observer model: A new method for estimating multispecies abundance
Authors: Golding Jessie D. , Nowak J. Joshua , Dreitz Victoria J.
Published: April 2017

Conservation of biological communities requires accurate estimates of abundance for multiple species. Recent advances in estimating abundance of multiple species, such as Bayesian multispecies N‐mixture models, account for multiple sources of variation, including detection error. However, false‐positive errors (misidentification or double counts), which are prevalent in multispecies data sets, remain largely unaddressed. The dependent‐double observer (DDO) method is an emerging method that both accounts for detection error and is suggested to reduce the occurrence of false positives because it relies on two observers working collaboratively to identify individuals. To date, the DDO method has not been combined with advantages of multispecies N‐mixture models. Here, we derive an extension of a multispecies N‐mixture model using the DDO survey method to create a multispecies dependent double‐observer abundance model (MDAM). The MDAM uses a hierarchical framework to account for biological and observational processes in a statistically consistent framework while using the accurate observation data from the DDO survey method. We demonstrate that the MDAM accurately estimates abundance of multiple species with simulated and real multispecies data sets. Simulations showed that the model provides both precise and accurate abundance estimates, with average credible interval coverage across 100 repeated simulations of 94.5% for abundance estimates and 92.5% for detection estimates. In addition, 92.2% of abundance estimates had a mean absolute percent error between 0% and 20%, with a mean of 7.7%. We present the MDAM as an important step forward in expanding the applicability of the DDO method to a multispecies setting. Previous implementation of the DDO method suggests the MDAM can be applied to a broad array of biological communities. We suggest that researchers interested in assessing biological communities consider the MDAM as a tool for deriving accurate, multispecies abundance estimates.
Riparian plant composition along hydrologic gradients in a dryland river basin and implications for a warming climate
Authors: Reynolds Lindsay V. , Shafroth Patrick B.
Published: April 2017

Droughts in dryland regions on all continents are expected to increase in severity and duration under future climate projections. In dryland regions, it is likely that minimum streamflow will decrease with some perennial streams shifting to intermittent flow under climate‐driven changes in precipitation and runoff and increases in temperature. Decreasing base flow and shifting flow regimes from perennial to intermittent could have significant implications for stream‐dependent biota, including riparian vegetation. In this study, we asked, how do riparian plant communities vary along wet‐to‐dry hydrologic gradients on small (first–third order) streams? We collected data on geomorphic, hydrologic, and plant community characteristics on 54 stream sites ranging in hydrology from intermittent to perennial flow across the Upper Colorado River Basin (284,898 km2). We found that plant communities varied along hydrologic gradients from high to low elevation between streams, and perennial to intermittent flow. We identified indicator species associated with different hydrologic conditions and suggest how plant communities may shift under warmer, drier conditions. Our results indicate that species richness and cover of total, perennial, wetland, and native plant groups will decrease while annual plants will increase under drying conditions. Understanding how plant communities respond to regional drivers such as hydroclimate requires broad‐scale approaches such as sampling across whole river basins. With increasingly arid conditions in many regions of the globe, understanding plant community shifts is key to understanding the future of riparian ecosystems.
Do benthic invertebrates use hyporheic refuges during streambed drying? A manipulative field experiment in nested hyporheic flowpaths
Authors: Maazouzi C. , Galassi D. , Claret C. , Cellot B. , Fiers F. , Martin D. , Marmonier P. , Dole‐Olivier M.‐J.
Published: April 2017

The existence of resilience mechanisms related to a disturbance, such as invertebrate migrations into the hyporheic zone (HZ, saturated subsurface interstices), promotes persistence of benthic communities in river ecosystems. Water exchanges through the HZ, which influence the distribution of biota, are heterogeneous at different scales, determining nested hyporheic flowpaths. The effect of these nested exchanges on the use of the hyporheic refuges by benthic invertebrates is still unknown. We simulated streambed drying in a stream section where hydrological exchanges were considered at riffle (upstream or downstream of riffles) and floodplain (downstream end of a floodplain) scales. Physicochemical indicators determined that local hyporheic flowpaths (up‐ and downwelling zones) were nested in a large‐scale downwelling section of the river. In this situation, the effect of 24 h of experimental drying on the distribution of invertebrates was examined at three sediment depths to follow their migrations into the HZ. Whereas invertebrate assemblages did not change in the control channel, abundance of benthic invertebrate increased in the HZ of the impact channel (up to seven‐fold). Changes occurred rapidly (15–24 h) and only upstream of riffle where surface water down‐welled. The migration was taxon‐specific and concerned the most abundant benthic taxa that temporarily colonize the HZ (“temporary hyporheos,” e.g., Leuctra cf. fusca, Baetis sp., Caenis sp., Orthocladiinae, Tanypodinae). In the context of climate change, hyporheic refuge use will promote persistence of communities facing the increasing frequency of extreme hydrological events. Improved knowledge about the distribution and function of these refuges is becoming crucial for river managers.
Soil respiration and mass balance estimation of fine root production in Fitzroya cupressoides forests of southern Chile
Authors: Urrutia‐Jalabert Rocio , Malhi Yadvinder , Lara Antonio
Published: April 2017

The soil carbon dynamics of southern hemisphere temperate rainforests have rarely been studied. Here, we report for the first time soil CO2 effluxes and their partitioning for medium‐age and old‐growth Fitzroya cupressoides forests growing under contrasting environmental conditions in the Coastal Range and Andean Cordillera of southern Chile. Fitzroya is a high biomass and one of the longest lived species in the world. We characterized soil respiration patterns over almost 2 yr. Annual soil respiration was slightly higher in younger forests from the Coastal Range compared with Andean forests during the first studied year (6.37–6.66 vs. 5.06–6.14 Mg C·ha−1·yr−1), and significantly higher during the second year mainly due to a warmer and drier summer (8.08–8.64 vs. 4.98–5.35 Mg C·ha−1·yr−1). Therefore, warmer and drier conditions, likely to become more common in this region under future climate change, were associated with significantly higher respiration in the shallow soils of the coast, but not in the Andes. A higher proportion of autotrophic respiration was found in the Coastal Range forest probably due to a much higher fine root biomass in this site. However, fine root productivity, an important contributor of belowground carbon fluxes, was a little lower (not significantly) in the coastal site (0.81 ± 0.60 vs. 1.50 ± 0.42 Mg C·ha−1·yr−1), indicating a longer root residence time in forests from this area. Soil CO2 effluxes from these forests and their root productivity are at the lower end of values recorded for other mature and old‐growth temperate wet forests worldwide. The intrinsic longevity and the particularly poor soils and rainy conditions where these forests grow may influence these facts. Interannual climate variability appears to be especially important for soil respiration in the Coastal Range due to the more Mediterranean climate influence and shallow, poor water retention soils in this area.
Climatic suitability ranking of biological control candidates: a biogeographic approach for ragweed management in Europe
Authors: Sun Yan , Brönnimann Olivier , Roderick George K. , Poltavsky Alexander , Lommen Suzanne T. E. , Müller‐Schärer Heinz
Published: April 2017

Biological control using natural antagonists has been a most successful management tool against alien invasive plants that threaten biodiversity. The selection of candidate agents remains a critical step in a biocontrol program before more elaborate and time‐consuming experiments are conducted. Here, we propose a biogeographic approach to identify candidates and combinations of candidates to potentially cover a large range of the invader. We studiedAmbrosia artemisiifolia(common ragweed), native to North America (NA) and invasive worldwide, and sixNAbiocontrol candidates for the introduced Europe (EU) range of ragweed, both under current and future bioclimatic conditions. For the first time, we constructed species distribution models based on worldwide occurrences and important bioclimatic variables simultaneously for a plant invader and its biocontrol candidates in view of selecting candidates that potentially cover a large range of the target invader. Ordination techniques were used to explore climatic constraints of each species and to perform niche overlap tests with ragweed. We show a large overlap in climatic space between candidates and ragweed, but a considerable discrepancy in geographic range overlap betweenEU(31.4%) andNA(83.3%). This might be due to niche unfilling and expansion of ragweed inEUand the fact that habitats with high ragweed occurrences inEUare rare inNAand predicted to be unsuitable for the candidates. Total geographic range of all candidates combined is expected to decrease under climate change in both ranges, but they will respond differently. The relative geographic coverage of a plant invader by biocontrol candidates at home is largely transferable to the introduced range, even when the invader shifts its niche. Our analyses also identified which combination of candidates is expected to cover the most area and for which abiotic conditions to select in order to develop climatically adapted strains for particular regions, where ragweed is currently unlikely to be controlled.
Grassland restoration in northern China is far from complete: evidence from carbon variation in the last three decades
Authors: Ma Anna , He Nianpeng , Xu Li , Wang Qiufeng , Li Meiling , Yu Guirui
Published: April 2017

Ecosystem restoration requires considering both above‐ground biomass (AGB) and soils, and the latter is even more essential due to the importance and restoration difficulty of soil organic matter (SOM). Remote sensing studies have shown that AGB has recovered in the grasslands of northern China, but the recovery of soil organic carbon (SOC) or SOM is still unclear. Here, based on the published data between the 1980s and 2014, we used the variation in carbon (C) density observed in the vegetation and soils of four regions across northern China as integrative indicator to explore grassland restoration. Overall, northern Chinese grasslands were a weak carbon source (−14 Tg C), although C density in AGB and below‐ground biomass increased on average by 0.019 and 0.224 kg C/m2, respectively, during the period considered in the present study. Unexpectedly, SOC density in the 0–20 cm soil layer decreased by 0.193 kg C/m2 on average, and all regions registered a decrease in SOC, although values differed among them. Our findings were consistent with previous evaluations using remote sensing and with the idea that vegetation in northern China has been restored. However, SOC has not been restored, and given its importance for sustaining nutrient supply and water conservation, as well as the high difficulty of SOC restoration, grassland restoration in northern China is still far from being achieved.
Polyunsaturated fatty acids in fishes increase with total lipids irrespective of feeding sources and trophic position
Authors: Kainz M. J. , Hager H. H. , Rasconi S. , Kahilainen K. K. , Amundsen P.‐A. , Hayden B.
Published: April 2017

Trophic transfer and retention of dietary compounds are vital for somatic development, reproduction, and survival of aquatic consumers. In this field study, stable carbon and nitrogen isotopes, and fatty acids (FA) contents in invertebrates and fishes of pre‐alpine Lake Lunz, Austria, were used to (1) identify the resource use and trophic level of Arctic charr (Salvelinus alpinus), pike (Esox lucius), perch (Perca fluviatilis), brown trout (Salmo trutta), roach (Rutilus rutilus), and minnow (Phoxinus phoxinus) and (2) examine how polyunsaturated fatty acids (PUFA; i.e., omega‐3 and ‐6PUFA) are related to total lipid status, littoral–pelagic reliance, and trophic position. Stable isotope data suggest that pike, perch, and minnow derived most of their energy from littoral resources, but minnows differed from pike and perch in their trophic position andPUFAcomposition. The co‐occurrence of cyprinids, percids, and pike segregated these fishes into more lipid‐rich (roach, minnow) and lipid‐poor (pike, percids) species. Although the relatively lipid‐poor pike and percids occupied a higher trophic position than cyprinids, there was a concurrent, total lipid‐dependent decline in omega‐3 and ‐6PUFAin these predatory fishes. Results of this lake food‐web study demonstrated that total lipids in fish community, littoral–pelagic reliance, and trophic position explained omega‐3 and ‐6PUFAin dorsal muscle tissues. Omega‐3 and ‐6PUFAin these fishes decreased with increasing trophic position, demonstrating that these essential FAs did not biomagnify with increasing trophic level. Finally, this lake food‐web study provides evidence of fish community‐level relationship between total lipid status andPUFAor stable isotope ratios, whereas the strength of such relationships was less strong at the species level.
Mechanistic species distribution modeling reveals a niche shift during invasion
Authors: Chapman Daniel S. , Scalone Romain , Štefanić Edita , Bullock James M.
Published: April 2017

Niche shifts of nonnative plants can occur when they colonize novel climatic conditions. However, the mechanistic basis for niche shifts during invasion is poorly understood and has rarely been captured within species distribution models. We quantified the consequence of between‐population variation in phenology for invasion of common ragweed (Ambrosia artemisiifolia L.) across Europe. Ragweed is of serious concern because of its harmful effects as a crop weed and because of its impact on public health as a major aeroallergen. We developed a forward mechanistic species distribution model based on responses of ragweed development rates to temperature and photoperiod. The model was parameterized and validated from the literature and by reanalyzing data from a reciprocal common garden experiment in which native and invasive populations were grown within and beyond the current invaded range. It could therefore accommodate between‐population variation in the physiological requirements for flowering, and predict the potentially invaded ranges of individual populations. Northern‐origin populations that were established outside the generally accepted climate envelope of the species had lower thermal requirements for bud development, suggesting local adaptation of phenology had occurred during the invasion. The model predicts that this will extend the potentially invaded range northward and increase the average suitability across Europe by 90% in the current climate and 20% in the future climate. Therefore, trait variation observed at the population scale can trigger a climatic niche shift at the biogeographic scale. For ragweed, earlier flowering phenology in established northern populations could allow the species to spread beyond its current invasive range, substantially increasing its risk to agriculture and public health. Mechanistic species distribution models offer the possibility to represent niche shifts by varying the traits and niche responses of individual populations. Ignoring such effects could substantially underestimate the extent and impact of invasions.
Triheterometallic Lanthanide Complexes Prepared from Kinetically Inert Lanthanide Building Blocks
Authors: Sørensen Thomas Just , Tropiano Manuel , Kenwright Alan M. , Faulkner Stephen
Published: April 2017

Invited for the cover of this issue is the group of ThomasàJust Sørensen from the University of Copenhagen, Denmark, in collaboration with the group of Stephen Faulkner from Oxford University, UK. The cover image shows the antenna effect, which enhances lanthanide‐centered emission.
An Overview of 2‐Styrylchromones: Natural Occurrence, Synthesis, Reactivity and Biological Properties
Authors: Santos Clementina M. M. , Silva Artur M. S.
Published: April 2017

2‐Styrylchromones are a small class of oxygen‐containing heterocycles. Despite their sparse occurrence in nature, several synthetic approaches have been developed in order to synthesize a large variety of derivatives, possessing different substituents in different positions of the main core. They are also versatile building blocks in the synthesis of new heterocyclic systems and important intermediates in the search for bioactive compounds. It is our intention in this review to give a general overview on the natural occurrence, synthesis, reactivity and biological properties of 2‐styrylchromones, which were published up until 2016.
Access to an anti,syn‐1,5,7‐Triol by Configuration‐Encoded 1,5‐Polyol Synthesis: The C15–C25 Fragment of Tetrafibricin
Authors: Friedrich Ryan M. , Friestad Gregory K.
Published: April 2017

A configuration‐encoded strategy provides unambiguous stereocontrol in an efficient synthesis of 1,5‐polyols. To access the anti,syn‐1,5,7‐triol moiety of the C15–C25 fragment of tetrafibricin, a fibrinogen receptor antagonist, a strategy is introduced, which sequences the 1,5‐polyol synthesis with selective desilylation and diastereoselective intramolecular conjugate addition. For tetrafibricin, assembly of the C15–C25 anti‐1,5‐diol in five steps is followed by the conjugate addition to introduce a syn‐1,3‐diol to complete the anti,syn‐1,5,7‐triol unit and to provide the functionality and stereochemistry required for tetrafibricin synthesis.
Metal Coordination Controlled and Bifunctional H‐Bonded Catalysis in Stereoselective Intramolecular Aldol Cyclizations toward Carbocyclic Tertiary β‐Ketols
Authors: Chen Bin , Berger Gilles , Hanessian Stephen
Published: April 2017

The principle of bifunctional catalysis is shown in the highly regio‐ and stereoselective intramolecular aldolization of 2‐methyl‐1,3‐cyclopentanedione, C2‐substituted with a methyl ethyl ketone group, to provide [3.2.1]‐bicyclooctanol diones in the presence of catalytic amounts of either LiBr and 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU), or 1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene (TBD). Mechanistic investigations corroborated by DFT calculations show that LiBr engages in a bifunctional coordination of two carbonyl moieties and leads to the preorganization of the reactive enolate intermediate for a base‐mediated intramolecular aldol cyclization. On the other hand, TBD catalysis of the triketone substrate proceeds through a bifunctional H‐bonded mechanism to give the same aldol product as the major diastereomer. The LiBr and TBD‐catalyzed highly stereocontrolled intramolecular aldol cyclizations can be extended to other di‐ and triketones to give carbocyclic and carbobicyclic products as single diastereomers.
Preparation of Indium Tin Oxide Nanoparticle‐modified 3‐Aminopropyltrimethoxysilane‐functionalized Indium Tin Oxide Electrode for Electrochemical Sulfide Detection
Authors: Aziz Md. Abdul , Mahfoz Wael , Nasiruzzaman Shaikh M. , Zahir Md. Hasan , Al‐Betar Abdul‐Rahman , Oyama Munetaka , Theleritis Demetrios , Yamani Zain Hassan
Published: April 2017

A sulfide sensor based on an indium tin oxide nanoparticle (ITONP)‐modified ITO electrode was developed. To prepare ITONP‐modified ITO, various methods were tested. Drop‐drying of ITONPs (aq.) on aminopropyltrimethoxysilane‐functionalized ITO (APTMS/ITO) was found to be the best method on the basis of voltammetric analysis of the sulfide ion. ITONP‐modified APTMS/ITO (ITONP/APTMS/ITO) yielded much better electrocatalytic properties toward sulfide electro‐οxidation than did bare or APTMS/ITO electrodes. The ITONPs and ITONP‐modified ITO were also characterized using transmission electron microscopy and field emission scanning electron microscopy, respectively. Optimization of the type of inert electrolyte and pH yielded an ITONP/APTMS/ITO detector whose amperometrically and chronocoulοmetrically determined limits of detection for sulfide were 3.0 μM and 0.90 μM, respectively. ITONP/APTMS/ITO electrodes displayed reproducible performance, were highly stable, and were not susceptible to interference by common contaminants. Thus, the developed electrode can be considered as a promising tool for sensing sulfide.
Evidence of significant forward rupture directivity aggravated by soil response in an Mw6 earthquake and the effects on monuments
Authors: Garini E. , Gazetas G. , Anastasopoulos I.
Published: April 2017

While strong directivity effects have been mostly recognized in Mw > 6.5 earthquakes, the paper investigates the case of a strong such effect in a relatively small‐magnitude event on 3 February 2014 in the island of Cephalonia, Greece. The second of two events (both of Mw ≈ 6) produced a pernicious accelerogram in the region's main town, Lixouri. The paper provides evidence from geology, interferometry, and seismology to convince that the motion was the result of constructive interference in front of the direction of rupture of the obliquely‐strike‐slip fault. The nature of the record is explored to demonstrate that its frequency content, its high velocity pulse, and its strong fault‐normal (FN) favorable polarity are associated with directivity. Moreover, the broad spectral acceleration peak (of 1.7 g) of the FN motion, centered at a period (T ≈ 1.4 s) which almost coincides with the period of the velocity pulse, is shown to have also been affected by soil amplification, in quantitative agreement with Bray et al. (2009). Such a directivity‐and‐soil‐affected motion explains much of the profound damage to monuments, slopes, and harbor quaywalls. In particular, toppling (as well as excessive rotation and sliding) of nearly‐all the tombstones in Lixouri cemetery are shown to correlate well with characteristics of the FN component of motion. By contrast, the excellent performance of the building stock — despite the destructive shaking that prevailed — is persuasively attributed to conservatively‐robust construction practices of the past and the high base shear coefficient of the strict latest (2000) seismic code. Copyright © 2017 John Wiley & Sons, Ltd.
Visualising the global environmental: new research directions
Authors: Grevsmühl Sebastian Vincent
Published: April 2017

This special issue on the visual cultures of global environmental issues proposes innovative research directions by introducing new methodological frameworks and profoundly rethinking the crucial role of the visual in environmental research. The five papers gathered here were written by researchers coming from various disciplinary and cultural backgrounds, thus helping bridge the divides between different disciplinary traditions. Each essay examines the notion of the ‘global environment’, and of ‘global environmental images’ in particular, from a different theoretical perspective. From these emerge shared concerns about underlying aesthetics and politics, and reflections on the tensions that arise when visualising the environment, especially when objects and theories are at a global scale. In this introduction, I reflect upon two aspects across the five papers exploring tensions between the ‘local’ and the ‘global’, as well as the politics of images within global environmental research. Considered as anensemble, this special issue calls for sustained interdisciplinary inquiry into global environmental images, paying close attention to the nature of this new type of global knowledge, the imaginaries mobilised, as well as the politics, power struggles, asymmetries and marginalisation processes which are inevitably involved when talking about the global environment.
Effectiveness of incorporating cetuximab into docetaxel/cisplatin/fluorouracil induction chemotherapy and chemoradiotherapy for inoperable squamous cell carcinoma of the oral cavity: A phase II study
Authors: Chang Peter Mu‐Hsin , Lu Hsueh‐Ju , Wang Ling‐Wei , Tai Shyh‐Kuan , Chen Ming‐Huang , Chu Pen‐Yuan , Yang Muh‐Hwa
Published: April 2017

Background

Inoperable oral cavity squamous cell carcinoma (SCC) is a highly invasive disease associated with the extensive destruction of locoregional tissues and a dismal prognosis. Management strategies for these patients are limited.

Methods

This study was a single arm, prospective, open‐label phase II trial. A regimen consisting of cetuximab‐docetaxel, cisplatin, and fluorouracil (C‐TPF) followed by bio‐chemoradiotherapy (bio‐CRT) with cisplatin and cetuximab was administered to patients who responded to induction chemotherapy. The objective response rate to C‐TPF was the primary endpoint.

Results

Forty‐three patients were enrolled in this study. The objective response rate of C‐TPF was 88.4%; 88.9% (32/36) of the responders completed the full bio‐CRT course, and the objective response rate of bio‐CRT was 64.7%. The most common grade 3/4 adverse events for induction chemotherapy were leucopenia (32.6%) and febrile neutropenia (14.0%). The 1‐year progression‐free survival (PFS) and overall survival (OS) rates were 43% and 68%, respectively.

Conclusion

C‐TPF is an effective and tolerable induction chemotherapy regimen for inoperable oral cavity SCC.
Matched cohort study of external cephalic version in women with previous cesarean delivery
Authors: Keepanasseril Anish , Anand Keerthana , Soundara Raghavan Subrahmanian
Published: April 2017

Objective

To evaluate the efficacy and safety of external cephalic version (ECV) among women with previous cesarean delivery.

Methods

A retrospective study was conducted using data for women with previous cesarean delivery and breech presentation who underwent ECV at or after 36 weeks of pregnancy during 2011–2016. For every case, two multiparous women without previous cesarean delivery who underwent ECV and were matched for age and pregnancy duration were included. Characteristics and outcomes were compared between groups.

Results

ECV was successful for 32 (84.2%) of 38 women with previous cesarean delivery and 62 (81.6%) in the control group (P=0.728). Multivariate regression analysis confirmed that previous cesarean was not associated with ECV success (odds ratio 1.89, 95% confidence interval 0.19–18.47; P=0.244). Successful vaginal delivery after successful ECV was reported for 19 (59.4%) women in the previous cesarean delivery group and 52 (83.9%) in the control group (P<0.001). No ECV‐associated complications occurred in women with previous cesarean delivery.

Conclusion

To avoid a repeat cesarean delivery, ECV can be offered to women with breech presentation and previous cesarean delivery who are otherwise eligible for a trial of labor.
Broaching Behaviors of Licensed Professional Counselors: A Qualitative Inquiry
Authors: Jones Connie T. , Welfare Laura E.
Published: April 2017

This qualitative study explored broaching behaviors of licensed professional Counselors during intakes with clients who have addictions. Five themes emerged: (a) to broach or not to broach, (b) follow the client's lead, (c) right timing, (d) counselor willingness, and (e) which cultural characteristics are considered.
Bactericidal effect of photocatalytically‐active nanostructured TiO2 surfaces on biofilms of the early oral colonizer, Streptococcus oralis
Authors: Westas Emma , Hayashi Mariko , Cecchinato Francesca , Wennerberg Ann , Andersson Martin , Jimbo Ryo , Davies Julia R
Published: April 2017

This study evaluated the photocatalytic bactericidal effect of nanostructured anatase‐rich titanium dioxide (TiO2) on microbial biofilms. Commercially pure titanium discs were spin‐coated with photocatalytic TiO2 nanoparticles (P25). Uncoated discs were used as control (CTRL). Half of the CTRL and half of the P25‐coated surfaces were coated with purified saliva (SAL) to give four different groups (CTRL, CTRL + SAL, P25 and P25 + SAL). Streptococcus oralis were allowed to form biofilms on the discs for 18 h and non‐adherent cells were rinsed off. Bacterial viability was assessed at time 0 with Live/Dead BacLight staining and epifluorescence microscopy. The remaining discs were divided into a non‐UV group and UVA‐irradiated (+UV) group (irradiation time, 6 or 24 h). Thereafter, viability was assessed as above. Viability at time 0 was high and no dead cells were seen on any of the surfaces, even after 24 h, in the absence of UVA. However, after 24 h of exposure, the proportion of viable cells was reduced by 40% on the P25 discs compared to 0 and 6 h, and this effect was enhanced with a salivary pellicle. Members of mixed species biofilms differ in their susceptibility to the bactericidal effect of the surfaces tested and further investigations are needed to optimize the conditions. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2321–2328, 2017.
Pharmacokinetics of Macitentan in Patients With Pulmonary Arterial Hypertension and Comparison With Healthy Subjects
Authors: Issac Milena , Dingemanse Jasper , Sidharta Patricia N.
Published: April 2017

Macitentan is a worldwide approved dual endothelin receptor antagonist that has demonstrated efficacy in the treatment of pulmonary arterial hypertension (PAH) in a phase 3 clinical trial, SERAPHIN, at a dose of 10 mg once daily. During this trial, trough plasma concentrations (Ctrough) of macitentan and its active metabolite,  ACT‐132577,  were obtained at steady state in 242 patients, indicating that mean Ctrough of both analytes was about 2‐fold higher in PAH patients than in healthy subjects. To further investigate the pharmacokinetics (PK) of macitentan and its active metabolite, ACT‐132577,  a 24‐hour PK profile was recorded at steady state in 20 PAH patients in the open‐label extension of SERAPHIN.  A cross‐study comparison showed that although Ctrough in PAH patients is higher when compared with a historical reference group of healthy subjects, with geometric mean ratios of 1.45 and 1.36 for macitentan and ACT‐132577, respectively, this does not translate to a significant difference in exposure expressed as maximum plasma concentration (Cmax) or area under the plasma concentration–time curve over a dosing interval (AUCτ). Geometric mean ratios for Cmax and AUCτ were 1.08 and 1.22, respectively, for macitentan and 1.24 and 1.31, respectively, for ACT‐132577. Therefore, overall exposure at steady state to macitentan and ACT‐132577 in PAH patients is considered similar to that in healthy subjects.
Sonographic diagnosis of acute mastoiditis and subsequent retroauricular abscess in a pediatric cochlear implant recipient: A case report
Authors: Sakaida Hiroshi , Usui Satoko , Matsuda Yasunori , Masuda Sawako , Takeuchi Kazuhiko
Published: April 2017

When acute mastoiditis occurs in cochlear implant recipients, it can progress to subsequent retroauricular abscess due to the absence of the external mastoid cortex resulting from mastoidectomy performed for cochlear implantation. The management goal is to control infection while preserving the implanted device. A 2‐year‐old boy with cochlear implants developed acute mastoiditis and a subsequent retroauricular abscess. The patient underwent a surgical intervention based on the diagnosis made utilizing gray‐scale and power Doppler sonography. This case illustrates the diagnostic usefulness of sonography in this rare situation. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:515–519, 2017
The impact of hyperglycemia on adhesion between endothelial and cancer cells revealed by single‐cell force spectroscopy
Authors: Malek‐Zietek Katarzyna E. , Targosz‐Korecka Marta , Szymonski Marek
Published: April 2017

The impact of hyperglycemia on adhesion between lung carcinoma cells (A549) and pulmonary human aorta endothelial cells (PHAEC) was studied using the single‐cell force spectroscopy. Cancer cells were immobilized on a tipless Atomic Force Microscopy (AFM) cantilever and a single layer of endothelial cells was prepared on a glass slide. The measured force‐distance curves provided information about the detachment force and about the frequency of specific ligand‐receptor rupture events. Measurements were performed for different times of short term (up to 2 h) and prolonged hyperglycemia (3 h ‐ 24 h). Single‐cell force results were correlated with the expression of cell adhesion molecules (intercellular adhesion molecule, P‐selectin) and with the length and density of the PHAECs glycocalyx layer, which were measured by AFM nanoindentation. For short‐term hyperglycemia, we observed a statistically significant increase of the adhesion parameters that was accompanied by an increase of the glycocalyx length and expression of P‐selectin. Removal of hyaluronic acid from PHAECs glycocalyx significantly decreased the adhesion parameters, which indicates that hyaluronic acid has a strong impact on adhesion in A549/PHAEC system in short term of hyperglycemia. For prolonged hyperglycemia, the most significant increase of adhesion parameters was observed for 24 hours and this phenomenon correlated with the expression of adhesion molecules and a decrease of the glycocalyx length. Taking together, presented data indicate that both mechanical and structural properties of the endothelial glycocalyx strongly modulate the adhesion in the A549/PHAEC system.