bluuebunny/crossref_metadata_2025 huggingface dataset:
Host plant density and patch isolation drive occupancy and abundance at a butterfly's northern range margin
Authors: Fourcade Yoan , Öckinger Erik
Published: December 2016

Marginal populations are usually small, fragmented, and vulnerable to extinction, which makes them particularly interesting from a conservation point of view. They are also the starting point of range shifts that result from climate change, through a process involving colonization of newly suitable sites at the cool margin of species distributions. Hence, understanding the processes that drive demography and distribution at high‐latitude populations is essential to forecast the response of species to global changes. We investigated the relative importance of solar irradiance (as a proxy for microclimate), habitat quality, and connectivity on occupancy, abundance, and population stability at the northern range margin of the Oberthür's grizzled skipper butterflyPyrgus armoricanus. For this purpose, butterfly abundance was surveyed in a habitat network consisting of 50 habitat patches over 12 years. We found that occupancy and abundance (average and variability) were mostly influenced by the density of host plants and the spatial isolation of patches, while solar irradiance and grazing frequency had only an effect on patch occupancy. Knowing that the distribution of host plants extends further north, we hypothesize that the actual variable limiting the northern distribution ofP. armoricanusmight be its dispersal capacity that prevents it from reaching more northern habitat patches. The persistence of this metapopulation in the face of global changes will thus be fundamentally linked to the maintenance of an efficient network of habitats.
Phylogeographic patterns of a lower intertidal isopod in the Gulf of California and the Caribbean and comparison with other intertidal isopods
Authors: Hurtado Luis A. , Mateos Mariana , Liu Shuang
Published: December 2016

A growing body of knowledge on the diversity and evolution of intertidal isopods across different regions worldwide has enhanced our understanding on biological diversification at the poorly studied, yet vast, sea–land interface. High genetic divergences among numerous allopatric lineages have been identified within presumed single broadly distributed species.Excirolana mayanais an intertidal isopod that is commonly found in sandy beaches throughout the Gulf of California. Its distribution in the Pacific extends from this basin to Colombia and in the Atlantic from Florida to Venezuela. Despite its broad distribution and ecological importance, its evolutionary history has been largely neglected. Herein, we examined phylogeographic patterns ofE. mayanain the Gulf of California and the Caribbean, based on maximum‐likelihood and Bayesian phylogenetic analyses ofDNAsequences from four mitochondrial genes (16SrDNA, 12SrDNA, cytochrome oxidase I gene, and cytochrome b gene). We compared the phylogeographic patterns ofE. mayanawith those of the coastal isopodsLigiaandExcirolana braziliensis(Gulf of California and Caribbean) andTylos(Gulf of California). We found highly divergent lineages in both, the Gulf of California and Caribbean, suggesting the presence of multiple species. We identified two instances of Atlantic–Pacific divergences. Some geographical structuring among the major clades found in the Caribbean is observed. Haplotypes from the Gulf of California form a monophyletic group sister to a lineage found in Venezuela. Phylogeographic patterns ofE. mayanain the Gulf of California differ from those observed inLigiaandTylosin this region. Nonetheless, several clades ofE. mayanahave similar distributions to clades of these two other isopod taxa. The high levels of cryptic diversity detected inE. mayanaalso pose challenges for the conservation of this isopod and its fragile environment, the sandy shores.
Using species distribution models to define nesting habitat of the eastern metapopulation of double‐crested cormorants
Authors: Sheehan Kate L. , Esswein Samuel T. , Dorr Brian S. , Yarrow Greg K. , Johnson Ron J.
Published: December 2016

When organisms with similar phenotypes have conflicting management and conservation initiatives, approaches are needed to differentiate among subpopulations or discrete groups. For example, the eastern metapopulation of the double‐crested cormorant (Phalacrocorax auritus) has a migratory phenotype that is culled because they are viewed as a threat to commercial and natural resources, whereas resident birds are targeted for conservation. Understanding the distinct breeding habitats of resident versus migratory cormorants would aid in identification and management decisions. Here, we use species distribution models (SDM: Maxent) of cormorant nesting habitat to examine the eastern P. auritus metapopulation and the predicted breeding sites of its phenotypes. We then estimate the phenotypic identity of breeding colonies of cormorants where management plans are being developed. We transferred SDMs trained on data from resident bird colonies in Florida and migratory bird colonies in Minnesota to South Carolina in an effort to identify the phenotype of breeding cormorants there based on the local landscape characteristics. Nesting habitat characteristics of cormorant colonies in South Carolina more closely resembled those of the Florida phenotype than those of birds of the Minnesota phenotype. The presence of the resident phenotype in summer suggests that migratory and resident cormorants will co‐occur in South Carolina in winter. Thus, there is an opportunity for separate management strategies for the two phenotypes in that state. We found differences in nesting habitat characteristics that could be used to refine management strategies and reduce human conflicts with abundant winter migrants and, at the same time, conserve less common colonies of resident cormorants. The models we use here show potential for advancing the study of geographically overlapping phenotypes with differing conservation and management priorities.
Comparative mitochondrial and chloroplast genomics of a genetically distinct form of Sargassum contributing to recent “Golden Tides” in the Western Atlantic
Authors: Amaral‐Zettler Linda A. , Dragone Nicholas B. , Schell Jeffrey , Slikas Beth , Murphy Leslie G. , Morrall Clare E. , Zettler Erik R.
Published: December 2016

Over the past 5 years, massive accumulations of holopelagic species of the brown macroalga Sargassum in coastal areas of the Caribbean have created “golden tides” that threaten local biodiversity and trigger economic losses associated with beach deterioration and impact on fisheries and tourism. In 2015, the first report identifying the cause of these extreme events implicated a rare form of the holopelagic species Sargassum natans (form VIII). However, since the first mention of S. natans VIII in the 1930s, based solely on morphological characters, no molecular data have confirmed this identification. We generated full‐length mitogenomes and partial chloroplast genomes of all representative holopelagic Sargassum species, S. fluitans III and S. natans I alongside the putatively rare S. natans VIII, to demonstrate small but consistent differences between S. natans I and VIII (7 bp differences out of the 34,727). Our comparative analyses also revealed that both S. natans I and S. natans VIII share a very close phylogenetic relationship with S. fluitans III (94‐ and 96‐bp differences of 34,727). We designed novel primers that amplified regions of the cox2 and cox3 marker genes with consistent polymorphic sites that enabled differentiation between the two S. natans forms (I and VIII) from each other and both from S. fluitans III in over 150 Sargassum samples including those from the 2014 golden tide event. Despite remarkable gene synteny and sequence conservation, the three Sargassum forms differ in morphology, ecology, and distribution patterns, warranting more extensive interrogation of holopelagic Sargassum genomes as a whole.
Intensified wind pollination mediated by pollen dimorphism after range expansion in an ambophilous biennialAconitum gymnandrum
Authors: Wang Lin‐Lin , Zhang Chan , Yang Ming‐Liu , Zhang Guo‐Peng , Zhang Zhi‐Qiang , Yang Yong‐Ping , Duan Yuan‐Wen
Published: December 2016

Pollination systems and associated floral traits generally differ between core and marginal populations of a species. However, such differences are rarely examined in plants with a mixed wind‐ and bumblebee‐pollination system, and the role of wind pollination during range expansion in ambophilous plants remains unclear. We compared floral traits and the contributions of bumblebee and wind pollination in refugium and marginal populations of the ambophilous plantAconitum gymnandrum. We found that most floral traits differed between the two populations, and those traits associated with the shift to wind pollination were pronounced in the marginal population. Bumblebee visitation rates varied significantly, but were generally low in the marginal population. Wind pollination occurred in both populations, and the efficiency was lower than that of bumblebee pollination. Two types of pollen grains, namely round and fusiform pollen, were transported to a stigma by bumblebees and wind, but fusiform pollen contributed to wind pollination to a larger degree, especially in the marginal population. Our results suggest that wind pollination was enhanced by pollen dimorphism in the marginal population ofA. gymnandrum, and wind pollination may provide reproductive assurance when bumblebee activity is unpredictable during range expansion, indicating that ambophily is stable in this species and shift in pollination system could be common when plants colonize new habitats.
Vertebrate defense against parasites: Interactions between avoidance, resistance, and tolerance
Authors: Klemme Ines , Karvonen Anssi
Published: December 2016

Hosts can utilize different types of defense against the effects of parasitism, including avoidance, resistance, and tolerance. Typically, there is tremendous heterogeneity among hosts in these defense mechanisms that may be rooted in the costs associated with defense and lead to trade‐offs with other life‐history traits. Trade‐offs may also exist between the defense mechanisms, but the relationships between avoidance, resistance, and tolerance have rarely been studied. Here, we assessed these three defense traits under common garden conditions in a natural host–parasite system, the trematode eye‐flukeDiplostomum pseudospathaceumand its second intermediate fish host. We looked at host individuals originating from four genetically distinct populations of two closely related salmonid species (Atlantic salmon,Salmo salarand sea trout,Salmo trutta trutta) to estimate the magnitude of variation in these defense traits and the relationships among them. We show species‐specific variation in resistance and tolerance and population‐specific variation in resistance. Further, we demonstrate evidence for a trade‐off between resistance and tolerance. Our results suggest that the variation in host defense can at least partly result from a compromise between different interacting defense traits, the relative importance of which is likely to be shaped by environmental components. Overall, this study emphasizes the importance of considering different components of the host defense system when making predictions on the outcome of host–parasite interactions.
Difference in response of water use to evaporative demand for codominant diffuse‐porous versus ring‐porous tree species under N addition in a temperate forest
Authors: Ouyang Lei , Zhao Ping , Zhu Liwei , Zhang Zhenzhen , Zhao Xiuhua , Ni Guangyan
Published: December 2016

In this study, we explored the impacts of nitrogen (N) addition on water transpiration of codominant trees with different wood anatomy and their response of water use to varying vapor pressure deficit (VPD). Three tree species, diffuse‐porous Liquidambar formosana Hance (maple), ring‐porous Quercus variabilis Blume (cork oak), and Quercus acutissima Carruth (sawtooth oak), were selected for this research. These temperate forest trees grow in a climatic transitional zone located in Henan Province of Central China, and have been under N addition treatments of different levels since April 2013. The N treatments include control, low N (25 kg N ha−1 year−1), and high N levels (50 kg N ha−1 year−1). The measured data of stem sap flow from April to October 2015 showed that maple trees used more water than oak trees and N addition generally decreased the water transport of maple and sawtooth oak but induced no significant change of water transpiration for cork oak. Water use in maple increased with VPD, whereas relatively flat response for both oaks was observed, suggesting a much stricter stomatal control. Under N addition, water transport in all tree species showed a significant decline in the wet period (August), during which there were more precipitation and cloudy days than in dry May when VPD is >1.80 kPa. However, changes of vessel size, hydraulic conductivity, and root biomass that are associated with N addition for both ring‐ and diffuse‐porous species remain unknown and require further investigation.
Structured decision making as a framework for large‐scale wildlife harvest management decisions
Authors: Robinson Kelly F. , Fuller Angela K. , Hurst Jeremy E. , Swift Bryan L. , Kirsch Arthur , Farquhar James , Decker Daniel J. , Siemer William F.
Published: December 2016

Fish and wildlife harvest management at large spatial scales often involves making complex decisions with multiple objectives and difficult tradeoffs, population demographics that vary spatially, competing stakeholder values, and uncertainties that might affect management decisions. Structured decision making (SDM) provides a formal decision analytic framework for evaluating difficult decisions by breaking decisions into component parts and separating the values of stakeholders from the scientific evaluation of management actions and uncertainty. The result is a rigorous, transparent, and values‐driven process. This decision‐aiding process provides the decision maker with a more complete understanding of the problem and the effects of potential management actions on stakeholder values, as well as how key uncertainties can affect the decision. We use a case study to illustrate how SDM can be used as a decision‐aiding tool for management decision making at large scales. We evaluated alternative white‐tailed deer (Odocoileus virginianus) buck‐harvest regulations in New York designed to reduce harvest of yearling bucks, taking into consideration the values of the state wildlife agency responsible for managing deer, as well as deer hunters. We incorporated tradeoffs about social, ecological, and economic management concerns throughout the state. Based on the outcomes of predictive models, expert elicitation, and hunter surveys, the SDM process identified management alternatives that optimized competing objectives. The SDM process provided biologists and managers insight about aspects of the buck‐harvest decision that helped them adopt a management strategy most compatible with diverse hunter values and management concerns.
Early warning signals, nonlinearity, and signs of hysteresis in real ecosystems
Authors: Litzow Michael A. , Hunsicker Mary E.
Published: December 2016

Early warning signals (EWS) might dramatically improve our ability to manage nonlinear ecological change. However, the degree to which theoretical EWS predictions are supported in empirical systems remains unclear. The goal of this study is to make recommendations for identifying the types of ecological transitions that are expected to show EWS. We conducted a review and meta‐analysis of published studies and comparative analysis of eight northeast Pacific Ocean time series to illustrate the importance of testing for nonlinearity in empirical EWS studies. We found that published studies demonstrating nonlinearity in ecosystem dynamics are more likely to support EWS predictions than studies with linear or undetermined dynamics. The northeast Pacific time series in our analysis were often too short for formal tests of nonlinearity, a common problem in empirical studies. To assess the evidence for nonlinear dynamics in these data, we tested for state‐dependent driver–response relationships consistent with hysteresis, a central feature of nonlinear ecological models. This analysis supported the results of the literature meta‐analysis. Four time series with driver–response relationships consistent with hysteresis generally supported theoretical EWS predictions, while four without evidence of hysteresis failed to support EWS predictions. Theoretical support for EWS is largely generated from nonlinear models, and we conclude that tests for either nonlinear dynamics or hysteresis are needed before employing EWS.
Non‐native introductions influence fish body size distributions within a dryland river
Authors: Fritschie Keith J. , Olden Julian D.
Published: December 2016

A contemporary challenge in ecology is assessing the ecosystem effects of multispecies introductions. Quantifying shifts in body sizes, a common trait with which many per capita rates of ecosystems functioning scales, provide an important way forward. Evidence suggests that freshwater fish introductions have altered species‐level body size distributions globally, but it is difficult to interpret their functional consequences because animals contribute to ecosystem functioning at the individual level at smaller spatial scales. In this study, we determine whether these macroecological patterns hold for individual size distributions (ISDs) at local scales. We use a comprehensive dataset of fish communities in a highly invaded dryland river to (1) compare the statistical moments of ISDs between native and non‐native pools and (2) relate biological and environmental covariates to the univariate moments of local ISDs and the multivariate community structure of local fish assemblages. We found that ISDs of native and non‐native pools were significantly different when data were pooled across sites. Non‐natives had smaller mean body size than natives across all guilds and within invertivore and omnivore guilds, but were significantly larger within the invertivore–piscivore guild. Moreover, differences in the variance of size distributions were often relatively greater than differences in the mean. By modeling ISDs at the site level as a function of biological and environmental covariates, we found that non‐native dominance within sites had similar effects on ISDs as expected from differences between species pools. However, neither biological nor environmental predictors explained significant community‐level variation when size and trophic structure were considered simultaneously. Shifts in size distributions can have multiple ecological consequences, and our results provide a baseline for generating size‐based predictions of non‐native species’ roles in ecosystem functioning. However, these size‐based predictions should be considered alongside other important trait distributions such as trophic structure, which had no consistent relationship with non‐native dominance in this study.
Pathogen dynamics during invasion and establishment of white‐nose syndrome explain mechanisms of host persistence
Authors: Frick Winifred F. , Cheng Tina L. , Langwig Kate E. , Hoyt Joseph R. , Janicki Amanda F. , Parise Katy L. , Foster Jeffrey T. , Kilpatrick A. Marm
Published: December 2016

Disease dynamics during pathogen invasion and establishment determine the impacts of disease on host populations and determine the mechanisms of host persistence. Temporal progression of prevalence and infection intensity illustrate whether tolerance, resistance, reduced transmission, or demographic compensation allow initially declining populations to persist. We measured infection dynamics of the fungal pathogen Pseudogymnoascus destructans that causes white‐nose syndrome in bats by estimating pathogen prevalence and load in seven bat species at 167 hibernacula over a decade as the pathogen invaded, became established, and some host populations stabilized. Fungal loads increased rapidly and prevalence rose to nearly 100% at most sites within 2 yr of invasion in six of seven species. Prevalence and loads did not decline over time despite huge reductions in colony sizes, likely due to an extensive environmental reservoir. However, there was substantial variation in fungal load among sites with persisting colonies, suggesting that both tolerance and resistance developed at different sites in the same species. In contrast, one species disappeared from hibernacula within 3 yr of pathogen invasion. Variable host responses to pathogen invasion require different management strategies to prevent disease‐induced extinction and to facilitate evolution of tolerance or resistance in persisting populations.
Annexin A1 promotes timely resolution of inflammation in murine gout
Authors: Galvão Izabela , Vago Juliana P. , Barroso Livia C. , Tavares Luciana P. , Queiroz‐Junior Celso M. , Costa Vivian V. , Carneiro Fernanda S. , Ferreira Tatiana P. , Silva Patricia M. R. , Amaral Flávio A. , Sousa Lirlândia P. , Teixeira Mauro M.
Published: December 2016

Gout is a self‐limited inflammatory disease caused by deposition of monosodium urate (MSU) crystals in the joints. Resolution of inflammation is an active process leading to restoration of tissue homeostasis. Here, we studied the role of Annexin A1 (AnxA1), a glucocorticoid‐regulated protein that has anti‐inflammatory and proresolving actions, in resolution of acute gouty inflammation. Injection of MSU crystals in the knee joint of mice induced inflammation that was associated with expression of AnxA1 during the resolving phase of inflammation. Neutralization of AnxA1 with antiserum or blockade of its receptor with BOC‐1 (nonselective) or WRW4 (selective) prevented the spontaneous resolution of gout. There was greater neutrophil infiltration after challenge with MSU crystals in AnxA1 knockout mice (AnxA1−/−) and delayed resolution associated to decreased neutrophil apoptosis and efferocytosis. Pretreatment of mice with AnxA1‐active N‐terminal peptide (Ac2–26) decreased neutrophil influx, IL‐1β, and CXCL1 production in periarticular joint. Posttreatment with Ac2–26 decreased neutrophil accumulation, IL‐1β, and hypernociception, and improved the articular histopathological score. Importantly, the therapeutic effects of Ac2–26 were associated with increased neutrophils apoptosis and shortened resolution intervals. In conclusion, AnxA1 plays a crucial role in the context of acute gouty inflammation by promoting timely resolution of inflammation.
Iron(III) Half‐Sandwich Complexes of the Two‐Legged Piano‐Stool [CpFe(aryl)Cl] Type from the Corresponding Aryliron(II) Precursors
Authors: Bauer Heiko , Wallasch Mark W. , Wolmershäuser Gotthelf , Sun Yu , Sitzmann Helmut
Published: December 2016

Instead of reacting with the σ‐mesityliron(II) complex [Cp′′′Fe(σ‐C6H2Me3‐2,4,6)] (1; Cp′′′ = 1,2,4‐tri‐tert‐butylcyclopentadienyl) to form a cyclohexadienyl(cyclopentadienyl)iron(II) sandwich complex with palladium coordination to the ipso carbon atom of the six‐membered ring, palladium(II) chloride oxidized 1 to the mesityliron(III) complex [Cp′′′Fe(σ‐C6H2Me3‐2,4,6)Cl] (5) with a two‐legged piano‐stool geometry. The oxidation of [4CpFe(σ‐C6H2Me3‐2,4,6)] (4; 4Cp = tetraisopropylcyclopentadienyl) to [4CpFe(σ‐C6H2Me3‐2,4,6)Cl] (6) was accomplished with hexachloroethane. Two other derivatives, [4CpFe(σ‐C6H3iPr2‐2,6)Cl] (7) and [5CpFe(σ‐C6H3iPr2‐2,6)Cl] (8; 5Cp = pentaisopropylcyclopentadienyl), could also be obtained by the same method. The molecular structures of 5 and 6 are compared with the structure of the (tetraisopropylcyclopentadienyl)iron(III) dibromide [4CpFeBr2] (9), which was formed from the iron(II) analogue [4CpFe(µ‐Br)]2 during attempted nucleophilic substitution with an arylmagnesium bromide.
Pentamethylcyclopentadienyl‐Supported Cerocene(III) Complexes
Authors: Schneider David , Anwander Reiner
Published: December 2016

The trivalent ate complex [Cp*2CeCl2K(thf)] (Cp* = C5Me5) was used in a diverse set of salt metathesis reactions. Equimolar reactions with LiNiPr2, LiN(SiHMe2)2, KN(SiMe3)2, and LiCH2C6H4‐o‐NMe2 gave the alkali metal‐free complexes [Cp*2Ce(NiPr2)], [Cp*2Ce{N(SiHMe2)2}], [Cp*2Ce{N(SiMe3)2}], and [Cp*2Ce(CH2C6H4‐o‐NMe2)]. Employing [Cp*2CeCl2K(thf)] and KC≡CtBu in a 1:2 ratio produced a mixture of [Cp*2Ce(C≡CtBu)2Li(thf)] and [Cp*2Ce(C≡CtBu)]2(LiCl) that was difficult to separate. The reaction of [Cp*2CeCl2Li(Et2O)] with 2 equiv. of LiC≡CPh involved Cp* displacement and formation of the tetrametallic half‐sandwich complex [Cp*Ce(C≡CPh)2]4(LiCl). All complexes were characterized by single‐crystal X‐ray structure analysis. The distinct terminal bonding behavior of the similarly sized NiPr2 and N(SiHMe2)2, of which the latter revealed a strong Ce···HSi β‐diagostic interaction, is supported by distinct paramagnetic shifts of the amido substituents in the 1H NMR spectra. As examples, [Cp*2Ce{N(SiHMe2)2}] and [Cp*2Ce(C≡CtBu)2Li(thf)] were tested for oxidation reactions with 1,4‐benzoquinone and Ph3CCl, respectively.
Characterization and stability study of cranberry flavonoids in lipid liquid crystalline systems
Authors: Linkevičiūtė Aušra , Būdienė Jurga , Naujalis Evaldas , Katelnikovas Arturas , Barauskas Justas
Published: December 2016

The main objective of the present study was to investigate mixtures of soy phosphatidylcholine (SPC) and glycerol dioleate (GDO) as encapsulation matrices for cranberry flavonoids. The effects of flavonoids loading into non‐aqueous formulations, non‐lamellar liquid crystalline phases, and their colloidal dispersions were studied by using synchrotron small angle X‐ray diffraction, dynamic light scattering. Flavonoids incorporation is discussed with respect to the lipid aggregation behavior, self‐assembled nanostructure, and chemical stability by using antioxidant activity assay. The obtained results show that SPC/GDO‐based formulations can incorporate relatively high amounts of flavonoids and serve as liquid crystalline delivery vehicles in the form of bulk phases or colloidal dispersions.

Practical applications: Our results show that SPC/GDO‐based formulations can incorporate relatively high amounts of cranberry flavonoids. The effect flavonoid extracts on the nanostructure of bulk SPC/GDO LC phases are lipid weight ratio‐dependent. Flavonoids loaded into SPC/GDO‐based formulations and LC phases retain their antioxidant properties. The self‐assembled lipid liquid crystalline systems protect bioactive compounds from degradation. These facts are important for the community working in the field of self‐assembly of lipid structures, food chemistry, and delivery vehicles of nutraceuticals.

Soy phosphatidylcholine lipids (SPC) and glycerol dioleate (GDO) formed lipid‐based liquid crystal systems can be successfully applied for entrapment of natural cranberries flavonoids. After full hydration LC formulations can easily create self‐assembled non‐lamellar LC systems with different nanostructures. The stability studies have shown that the flavonoids loaded in SPC/GDO‐based systems retain their antioxidant properties at least up to 30 days.
First Detection of a Ruthenium–Carbene–Resorc[4]arene Complex During the Progress of a Metathesis Reaction
Authors: Aiello Federica , Balzano Federica , Ghirga Francesca , D'Acquarica Ilaria , Botta Bruno , Uccello‐Barretta Gloria , Quaglio Deborah
Published: December 2016

For the first time we describe the detection of a ruthenium‐carbene‐resorc[4]arene complex produced, as a key intermediate, during an olefin metathesis reaction carried out on a resorc[4]arene bicyclic olefin with [Ru(=CHPh)Cl2(PCy3)2] Grubbs first‐generation (G1ST) catalyst. The complex was identified by using high‐resolution (600 MHz) 1H, 31P NMR and DOSY spectroscopy, in a non‐invasive fashion. The singlet at δ = 19.98 ppm (1H NMR), attributed to the alkylidene proton in the G1ST catalyst and that at δ = 53.37 ppm (31P NMR), attributed to the phosphorus atom coordinated with the metal, were selected as probes for a kinetic analysis. The intensity of these signals decreased at the expense of the singlets at 19.26 (1H NMR) and 52.68 ppm (31P NMR), diagnostic for the formation of the ruthenium‐carbene‐resorc[4]arene complex 3a[Ru]. The resorc[4]arene activated olefin proved to behave as a key propagating species leading to oligomers according to a ROMP pathway.
An Enantio‐ and Diastereoselective Mannich/Pictet–Spengler Sequence To Form Spiro[piperidine‐pyridoindoles] and Application to Library Synthesis
Authors: Riesco‐Domínguez Alejandra , van der Zwaluw Nick , Blanco‐Ania Daniel , Rutjes Floris P. J. T.
Published: December 2016

A new tandem strategy based on a Mannich/Pictet–Spengler sequence has been developed and applied to the synthesis of a new small library (14 examples) of privileged compounds based on the spiro[piperidine‐pyridoindole] core. The sequence proceeds by a diastereoselective Pictet–Spengler cyclization after condensation of several tryptamine derivatives with three novel piperidin‐4‐ones containing the fluorinated substituents F, CF3 and SF5. The piperidin‐4‐ones were synthesized from readily available starting materials by an enantioselective multi‐component organocatalytic Mannich reaction.
Sequential analysis of 18 genes in polycythemia vera and essential thrombocythemia reveals an association between mutational status and clinical outcome
Authors: Luque Paz Damien , Chauveau Aurélie , Boyer Françoise , Buors Caroline , Samaison Laura , Cottin Laurane , Seegers Valérie , Férec Claude , Le Maréchal Cédric , Gueguen Paul , Lippert Eric , Ianotto Jean‐Christophe , Ugo Valérie
Published: December 2016

Philadelphia‐negative classical myeloproliferative neoplasms (MPN) are clonal diseases characterized by driver mutations of JAK2, MPL, or CALR. Additional mutations may occur in epigenetic regulators, signaling, or splicing genes that may be useful in the prognostic assessment of MPN patients. In primary myelofibrosis, molecular‐based prognostic scoring systems have been recently proposed, but few data are available to date for polycythemia vera (PV) and essential thrombocythemia (ET). In this study, we used a next generation sequencing‐based 18‐gene panel in 50 JAK2V617F positive PV and JAK2V617F positive ET patients from an institutional cohort investigated at diagnosis and at 3‐year follow‐up (3y). Disease progression at 3y was defined by a composite criterion. Patients (28 PV and 22 ET) were included according to their clinical status, with or without disease progression. At diagnosis, we found 28 additional mutations in 21 of the 50 patients. Patients with disease progression were more likely to have at least one additional mutation. There was no difference between PV and ET. All patients with two or more additional mutations exhibited disease progression at 3y. No novel mutations appeared at 3y. The allele burden increase by at least one mutation at 3y was more frequent in patients with disease progression. Our data suggest that screening for additional mutations in PV and ET could identify patients at a higher risk of disease progression. © 2017 Wiley Periodicals, Inc.
Synthesis of P‐stereogenic macrocycles
Authors: Kato Ryosuke , Fukuyama Misuzu , Morisaki Yasuhiro , Chujo Yoshiki
Published: December 2016

Optically active macrocycles consisting of two P‐stereogenic bisphosphine units and two π‐conjugated linkers were synthesized via [2 + 2] cyclization. A clear Cotton effect was observed in the π–π* transition region of the π‐conjugated units, indicating that the chirality is induced by the P‐stereogenic bisphosphine moieties onto the π‐conjugated linkers. Compared with model compounds, the orientation of the two π‐conjugated units was essential to the induced circular dichroism. Macrocycles containing extended π‐conjugated linkers exhibited large molar extinction coefficients, high photoluminescence quantum efficiencies, and intense circularly polarized luminescence with the large dissymmetry factors.
Role of immediate recurrent laryngeal nerve reconstruction in surgery for thyroid cancers with fixed vocal cords
Authors: Iwaki Shinobu , Maeda Tatsuyoshi , Saito Miki , Otsuki Naoki , Takahashi Miki , Wakui Emi , Shinomiya Hirotaka , Morimoto Koichi , Inoue Hiroyuki , Masuoka Hiroo , Miyauchi Akira , Nibu Ken‐ichi
Published: December 2016

Background

Quality of voice after immediate recurrent laryngeal nerve (RLN) reconstruction in thyroid cancers has not been thoroughly studied.

Methods

Thirteen patients with fixed vocal cords (fixed vocal cord group) and 8 patients with intact or impaired mobile vocal cords (mobile vocal cord group) who had immediate RLN reconstruction simultaneously with total thyroidectomy, and patients who had arytenoid adduction and thyroplasty for vocal cord paralysis caused by previous surgery (arytenoid adduction thyroplasty group) were enrolled in this study.

Results

Preoperative phonation efficiency index was significantly lower (p = .008) in the fixed vocal cord group than in the mobile vocal cord group. One year after surgery, all voice parameters of the patients in the fixed vocal cord group had improved, compared with their preoperative data. The fixed vocal cord group had attained satisfactory voice qualities equivalent to those of the mobile vocal cord group in terms of various voice parameters.

Conclusion

The present results support the idea that immediate RLN reconstruction at the time of surgery for thyroid cancers may spare the need for subsequent arytenoid adduction thyroplasty even in the patients with preoperatively fixed vocal cords. © 2016 Wiley Periodicals, Inc. Head Neck 39: 427–431, 2017
Investigation of arguments against properly indicated extracapsular dissection in the parotid gland
Authors: Mantsopoulos Konstantinos , Scherl Claudia , Iro Heinrich
Published: December 2016

Background

The ideal extent of surgical intervention for benign parotid tumors remains a matter of controversy. The purpose of this study was to examine the existing arguments against extracapsular dissection and present our experience over the last 16 years.

Methods

A retrospective evaluation was carried out on the records of all patients who underwent extracapsular dissection for benign parotid tumors at a tertiary referral center between 2000 and 2015.

Results

A total of 1359 cases were included in the study. Temporary postoperative facial palsy was detected in 68 cases (5%), permanent facial palsy in 5 cases (0.37%), and postoperative Frey's syndrome in 31 cases (2.3%). Recurrences of pleomorphic adenomas were shown in 4 cases (0.87%).

Conclusion

Our analysis could not justify the arguments against correctly indicated implementation of extracapsular dissection and showed that increased performance of this modality was associated with excellent oncologic and functional outcomes. © 2016 Wiley Periodicals, Inc. Head Neck 39: 498–502, 2017
Use of pretreatment serum uric acid level to predict metastasis in locally advanced nasopharyngeal carcinoma
Authors: Du Xiao‐Jing , Chen Lei , Li Wen‐Fei , Tang Ling‐Long , Mao Yan‐Ping , Guo Rui , Sun Ying , Lin Ai‐Hua , Ma Jun
Published: December 2016

Background

The purpose of this study was to determine the predictive value of pretreatment serum uric acid (SUA) for metastasis in locally advanced nasopharyngeal carcinoma (NPC) treated with intensity‐modulated radiotherapy.

Methods

This retrospective study examined 1063 patients with locally advanced NPC. Multivariate survival analysis was used.

Results

High pretreatment SUA level (>353.4 μmol/L) independently predicted distant metastasis‐free survival (p = .013) and was associated with high white blood cell (p = .005), lymphocyte counts (p < .001), and male sex (p < 0.001). In addition, SUA levels were significantly elevated in patients with T1 to T3 classification (p = .042). For patients with subsequent lung metastases after treatment, markedly higher pretreatment SUA levels were detected compared with patients who had other distant metastases (p =.012) and patients without distant metastasis (p = .024).

Conclusion

Pretreatment SUA may be a useful biomarker for evaluating treatment options for patients with locally advanced NPC. © 2016 Wiley Periodicals, Inc. Head Neck 39: 492–497, 2017
Stereotactic body radiotherapy for recurrent head and neck cancer: A critical review
Authors: Baliga Sujith , Kabarriti Rafi , Ohri Nitin , Haynes–Lewis Hilda , Yaparpalvi Ravindra , Kalnicki Shalom , Garg Madhur K
Published: December 2016

The management of patients with recurrent head and neck cancers remains a challenging clinical dilemma. Concerns over toxicity with re‐irradiation have limited its use in the clinical setting. Stereotactic Body Radiation Therapy (SBRT) has emerged as a highly conformal and precise type of radiotherapy and has the advantage of sparing normal tissue. Although SBRT is an attractive treatment modality, its use in the clinic is limited, given the technically challenging nature of the procedure. In this review, we attempt to provide a comprehensive overview of the role of re‐irradiation in patients with recurrent head and neck cancers, with particular attention to the advent of SBRT and its use with systemic therapies such as cetuximab. In the second portion of this review, we present our systematic review of published experiences with SBRT in recurrent head and neck cancers in an attempt to provide data on response rates (RR), overall survival and toxicity. © 2016 Wiley Periodicals, Inc. Head Neck 39: 595–601, 2017
The core domain of hepatitis C virus glycoprotein E2 generates potent cross‐neutralizing antibodies in guinea pigs
Authors: Vietheer Patricia T. , Boo Irene , Gu Jun , McCaffrey Kathleen , Edwards Stirling , Owczarek Catherine , Hardy Matthew P. , Fabri Louis , Center Rob J. , Poumbourios Pantelis , Drummer Heidi E.
Published: December 2016

A vaccine that prevents hepatitis C virus (HCV) infection is urgently needed to support an emerging global elimination program. However, vaccine development has been confounded because of HCV's high degree of antigenic variability and the preferential induction of type‐specific immune responses with limited potency against heterologous viral strains and genotypes. We showed previously that deletion of the three variable regions from the E2 receptor‐binding domain (Δ123) increases the ability of human broadly neutralizing antibodies (bNAbs) to inhibit E2‐CD81 receptor interactions, suggesting improved bNAb epitope exposure. In this study, the immunogenicity of Δ123 was examined. We show that high‐molecular‐weight forms of Δ123 elicit distinct antibody specificities with potent and broad neutralizing activity against all seven HCV genotypes. Antibody competition studies revealed that immune sera raised to high‐molecular‐weight Δ123 was poly specific, given that it inhibited the binding of human bNAbs directed to three major neutralization epitopes on E2. By contrast, the immune sera raised to monomeric Δ123 predominantly blocked the binding of a non‐neutralizing antibody to Δ123, while having reduced ability to block bNAb binding to E2, and neutralization was largely toward the homologous genotype. This increased ability of oligomeric Δ123 to generate bNAbs correlates with occlusion of the non‐neutralizing face of E2 in this glycoprotein form. Conclusion: The results from this study reveal new information on the antigenic and immunogenic potential of E2‐based immunogens and provide a pathway for the development of a simple, recombinant protein‐based prophylactic vaccine for HCV with potential for universal protection. (Hepatology 2017;65:1117‐1131).
The safety and effectiveness of ledipasvir−sofosbuvir in adolescents 12‐17 years old with hepatitis C virus genotype 1 infection
Authors: Balistreri William F. , Murray Karen F. , Rosenthal Philip , Bansal Sanjay , Lin Chuan‐Hao , Kersey Kathryn , Massetto Benedetta , Zhu Yanni , Kanwar Bittoo , German Polina , Svarovskaia Evguenia , Brainard Diana M. , Wen Jessica , Gonzalez‐Peralta Regino P. , Jonas Maureen M. , Schwarz Kathleen
Published: December 2016

No all‐oral, direct‐acting antiviral regimens have been approved for children with chronic hepatitis C virus (HCV) infection. We conducted a phase 2, multicenter, open‐label study to evaluate the efficacy and safety of ledipasvir–sofosbuvir in adolescents with chronic HCV genotype 1 infection. One hundred patients aged 12‐17 years received a combination tablet of 90 mg ledipasvir and 400 mg sofosbuvir once daily for 12 weeks. On the tenth day following initiation of dosing, 10 patients underwent an intensive pharmacokinetic evaluation of the concentrations of sofosbuvir, ledipasvir, and the sofosbuvir metabolite GS‐331007. The primary efficacy endpoint was the percentage of patients with a sustained virologic response at 12 weeks posttreatment. Median age of patients was 15 years (range 12‐17). A majority (80%) were HCV treatment‐naive, and 84% were infected through perinatal transmission. One patient had cirrhosis, and 42 did not; in 57 patients the degree of fibrosis was unknown. Overall, 98% (98/100; 95% confidence interval 93%‐100%) of patients reached sustained virologic response at 12 weeks. No patient had virologic failure. The 2 patients who did not achieve sustained virologic response at 12 weeks were lost to follow‐up either during or after treatment. The three most commonly reported adverse events were headache (27% of patients), diarrhea (14%), and fatigue (13%). No serious adverse events were reported. Area under the concentration‐time curve (tau) and maximum concentration values for sofosbuvir, ledipasvir, and GS‐331007 were within the predefined pharmacokinetic equivalence boundaries of 50%‐200% when compared with adults from phase 2 and 3 studies of ledipasvir and sofosbuvir. Conclusion: Ledipasvir−sofosbuvir was highly effective at treating adolescents with chronic HCV genotype 1 infection; the dose of ledipasvir−sofosbuvir currently used in adults was well tolerated in adolescents and had an appropriate pharmacokinetic profile. (Hepatology 2017;66:371–378).
Behavior‐dependent activity patterns of GABAergic long‐range projecting neurons in the rat hippocampus
Authors: Katona Linda , Micklem Ben , Borhegyi Zsolt , Swiejkowski Daniel A. , Valenti Ornella , Viney Tim J. , Kotzadimitriou Dimitrios , Klausberger Thomas , Somogyi Peter
Published: December 2016

Long‐range glutamatergic and GABAergic projections participate in temporal coordination of neuronal activity in distributed cortical areas. In the hippocampus, GABAergic neurons project to the medial septum and retrohippocampal areas. Many GABAergic projection cells express somatostatin (SOM+) and, together with locally terminating SOM+ bistratified and O‐LM cells, contribute to dendritic inhibition of pyramidal cells. We tested the hypothesis that diversity in SOM+ cells reflects temporal specialization during behavior using extracellular single cell recording and juxtacellular neurobiotin‐labeling in freely moving rats. We have demonstrated that rare GABAergic projection neurons discharge rhythmically and are remarkably diverse. During sharp wave‐ripples, most projection cells, including a novel SOM+ GABAergic back‐projecting cell, increased their activity similar to bistratified cells, but unlike O‐LM cells. During movement, most projection cells discharged along the descending slope of theta cycles, but some fired at the trough jointly with bistratified and O‐LM cells. The specialization of hippocampal SOM+ projection neurons complements the action of local interneurons in differentially phasing inputs from the CA3 area to CA1 pyramidal cell dendrites during sleep and wakefulness. Our observations suggest that GABAergic projection cells mediate the behavior‐ and network state‐dependent binding of neuronal assemblies amongst functionally‐related brain regions by transmitting local rhythmic entrainment of neurons in CA1 to neuronal populations in other areas. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.
Could the application of bioactive molecules improve vital pulp therapy success? A systematic review
Authors: Luiz de Oliveira da Rosa Wellington , Machado da Silva Tiago , Fernando Demarco Flávio , Piva Evandro , Fernandes da Silva Adriana
Published: December 2016

This study aimed to systematically review the literature of animal studies to evaluate whether bioactive dentin proteins could improve vital pulp therapy success. The review is reported in accordance with the PRISMA Statement. Two reviewers independently conducted a literature search of seven databases: PubMed (Medline), Lilacs, IBECS, BBO, Web of Science, Scopus, and SciELO. Animal experiments in which bioactive dentin proteins were applied directly or indirectly to the pulp tissue were included. Data regarding the characteristics of the proteins evaluated, the delivery systems used and the main findings from each study were tabulated to assess the outcomes of interest (tertiary dentin formation, inflammatory response, intratubular mineralization). After screening, 32 papers were subjected to qualitative analysis. In 75% of the studies, direct pulp capping was performed. Additionally, the most studied proteins were BMP‐7, TGF‐β1, and extracted soluble dentin matrix proteins. In conclusion, there is evidence in the literature suggesting that bioactive dentin molecules could enhance tertiary dentin formation with fewer initial inflammatory responses in direct and indirect pulp therapy in animal models. There are potential areas to be explored for novel therapeutic approaches for dental tissue repair and regeneration with bioactive materials. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 941–956, 2017.
Biodegradable nanocomplex from hyaluronic acid and arginine based poly(ester amide)s as the delivery vehicles for improved photodynamic therapy of multidrug resistant tumor cells: An in vitro study of the performance of chlorin e6 photosensitizer
Authors: Ji Ying , Zhao Jihui , Chu Chih‐Chang
Published: December 2016

Photodynamic therapy (PDT), which enables the localized therapeutic effect by light irradiation, provides an alternative and complementary modality for the treatment of tumor. However, the aggregation of photosensitizers in acidic microenvironment of tumor and the non‐targeted distribution of photosensitizers in normal tissues significantly affect the PDT efficiency. In this study, we developed a biodegradable nanocomplex HA‐Arg‐PEA from hyaluronic acid (HA) and arginine based poly(ester amide)s (Arg‐PEA) as the nanocarrier for chlorin e6 (Ce6). HA enhanced the tumor‐specific endocytosis mediated by the overexpression of CD44 receptor. Arg‐PEA not only provide electrostatic interaction with HA to form self‐assembled nanostructure, but also improve the monomerization of Ce6 at physiological pH as well as mildly acidic pH. The biodegradable characteristic of HA‐Arg‐PEA nanocomplex enabled the intracellular delivery of Ce6, in which its release and generation of singlet oxygen can be accelerated by enzymatic degradation of the carrier. The in vitro PDT efficiency of Ce6‐loaded HA‐Arg‐PEA nanocomplex was examined in CD44 positive MDA‐MB‐435/MDR multidrug resistant melanoma cells. CD44‐mediated uptake of Ce6‐loaded HA‐Arg‐PEA nanocomplex significantly improved Ce6 level in MDA‐MB‐435/MDR cells within short incubation time, and the PDT efficiency in inhibiting multidrug resistant tumor cells was also enhanced at higher Ce6 concentrations. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1487–1499, 2017.