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Biased activity of soluble guanylyl cyclase:the Janus face of thymoquinone

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Acta Pharmaceutica Sinica B 2017年第4期7卷 401-408页

作者： charlotte Detremmerie Paul m.Vanhoutte Susan Leung Department of Pharmacology and Pharmacy and State Key Laboratory for Pharmaceutical Biotechnology Li Ka Shing Faculty of Medicinethe University of Hong KongHong KongChina

The natural compound thymoquinone, extracted from Nigella sativa(black cumin), is widely used in humans for its anti-oxidative properties. Thymoquinone is known for its acute endotheliumindependent vasodilator effects in isolated rat aortae and pulmonary arteries, depending in part on activation of adenosine triphosphate-sensitive potassium channels and inhibition of voltage-dependent calcium channels. The compound also improves endothelial dysfunction in mesenteric arteries of ageing rodents and in aortae of rabbits treated with pyrogallol, by inhibiting oxidative stress. Serendipitously,thymoquinone was found to augment contractions in isolated arteries with endothelium of both rats and pigs. The endothelium-dependent augmentation it causes counterintuitively depends on biased activation of soluble guanylyl cyclase(sGC) producing inosine 3',5'-cyclic monophosphate(cyclic ImP) rather than guanosine 3',5'-cyclic monophosphate. This phenomenon shows a striking mechanistic similarity to the hypoxic augmentation previously observed in porcine coronary arteries. The cyclic ImP preferentially produced under thymoquinone exposure causes an increased contractility of arterial smooth muscle by interfering with calcium homeostasis. This brief review summarizes the vascular pharmacology of thymoquinone, focussing in particular on how the compound causes endothelium-dependent contractions by biasing the activity of sGC.

关键词： Thymoquinone Endothelium-dependentcontraction Nitric oxide Soluble guanylyl cyclase Cyclic ImP NADPH:quinone oxidoreductase

The Yin and Yang of Wnt/Ryk axon guidance in development and regeneration

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Science China(Life Sciences) 2014年第4期57卷 366-371页

作者： CLARK charlotte EJ LIU Yaobo COOPER Helen m Queensland Brain Institute The University of QueenslandBrisbane Institute of Neuroscience Soochow University

In the developing embryo,nascent axons navigate towards their specific targets to establish the intricate network of axonal connections linking neurons within the mature nervous *** navigational systems comprising repulsive and attractive guidance cues form chemotactic gradients along the pathway of the exploring growth ***-bound receptors detect these gradients and determine the trajectory of the migrating growth *** contrast to their benevolent role in the developing nervous system,repulsive guidance receptors are detrimental to the axon’s ability to regenerate after injury in the *** this review we explore the essential and beneficial role played by the chemorepulsive Wnt receptor,Ryk/Derailed in axon navigation in the embryonic nervous system(the Yin function).Specifically,we focus on the role of Wnt5a/Rykmediated guidance in the establishment of two major axon tracts in the mammalian central nervous system,the corticospinal tract and the corpus *** studies have also identified Ryk as a major suppressor of axonal regeneration after spinal cord ***,we also discuss this opposing aspect of Ryk function in axonal regeneration where its activity is a major impediment to axon regrowth(the Yang function).

关键词： Ryk Derailed Wnt Wnt signalling axon guidance axonal regeneration spinal cord injury

Detrital zircon U-Pb-He double dating: A method of quantifying long- and short-term exhumation rates in collisional orogens

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Science China Earth Sciences 2014年第11期57卷 2702-2711页

作者： Christina Yan WANG Ian H.CAmPBELL Peter W.REINERS charlotte m.ALLEN Key Laboratory of mineralogy and metallogeny Guangzhou Institute of Geochemistry Chinese Academy of Sciences Research School of Earth Sciences The Australian National UniversityCanberra ACT 0200 Australia Department of Geosciences University of ArizonaTucson AZ 85721 USA

A U-Pb-He double-dating method is applied to detrital zircons with core-rim structure from the Ganges River in order to de- termine average short and long-term exhumation rates for the Himalayas. Long-term rates are calculated from the U/Pb ages of metamorphic rims of the grains that formed during the Himalayan orogeny and their crystallization temperatures, which are calculated from the Ti-in-zircon thermometer. Short-term rates are calculated from （U-Th）/He ages of the grains with appro- priate closure temperatures. The results show that short-term rates for the Himalayas, which range from 0.70 ± 0.09 to 2.67 ± 0.40 km/myr and average 1.75 ± 0.59 （1δ） km/myr, are higher and more varied than the long-term rates, which range from 0.84 ±0.16 to 1.85 ± 0.35 km/myr and average 1.26 ±0.25 （let） km/myr. The differences between the long-term and short-term rates can be attributed to continuous exhumation of the host rocks in different mechanisms in continental collision orogen. The U/Pb ages of 44.0 ± 3.7 to 18.3 ±0.5 ma for the zircon rims indicate a protracted episode of -：25 myr for regional metamorphism of the host rocks at deeper crust, whereas the （U-Th）/He ages of 42.2 ± 1.8 to 1.3 ± 0.2 ma for the zircon grains represent a protracted period of -40 myr for exposure of the host rocks to shallower crustal level. In particular, the oldest （U-Th）/He ages of the zircon grains are close to the oldest U/Pb ages for the rims, indicating that some parcels of the rocks that contain zircons were rapidly exhumed from deep to shallow levels in the stage of collisional orogeny. On the other hand, some parcels of the rocks may have been carried upwards by thrust faults in the post-collisional stage. The parcels could be carried upwards by the thrust faults that steepen as they near the surface, or by transient movement faults so that areas of rapid exhu- mation became areas of slow exhumation and visa versa on a time scale of a few myr in order to maintain the continuous ex- huma

关键词： zircon U-Pb-He double-dating method Himalayas exhumation rate collisional orogen

Assessing animal individuality:links between personality and laterality in pigs

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Current Zoology 2019年第5期65卷 541-551页

作者： charlotte GOURSOT Sandra DUPJAN Ellen KANITZ Armin TUCHSCHERER Birger PUPPE Lisette m.C.LELIVELD Institute of Behavioural Physiology Leibniz Institute for Farm Animal Biology(FBN)Wilhelm-Stahl-Allee 2D-18196 DummerstorfGermany Institute of Genetics and Biometry Leibniz Institute for Farm Animal Biology(FBN)Wilhelm-Stahl-Allee 2D-18196 DummerstorfGermany Behavioural Sciences Faculty of Agricultural and Environmental SciencesUniversity of RostockJustus-von-Liebig-Weg 6BRostock D-18059Germany

Animal individuality is challenging to explain because individual differences are regulated by multiple selective forces that lead to unique combinations of *** instance,the study of personality,a core aspect of individuality,may benefit from integrating other factors underlying individual differences,such as lateralized cerebral ***,the approach-withdrawal hypothesis(the left hemisphere controls approach behavior,the right hemisphere controls withdrawal behavior),may account for differences in boldness or exploration between left and right hemispheric dominant *** analyze the relationships between personality and laterality we tested 80 male piglets with established laterality patterns for 2 motor functions(tail curling direction and the side of the snout used for manipulation)and a combined classification integrating both motor functions using cluster *** analyzed basal salivary testosterone and cortisol along with their behavior in standardized tests as pre-established indicators of different personality traits(Boldness,Exploration,Activity,Sociability,and Coping).We found that the direction of the single motor biases showed significant associations with few personality ***,the combined laterality classification showed more,and more robust,significant associations with different personality traits compared with the single motor *** results supported the approachwithdrawal hypothesis because right-biased pigs were bolder and more explorative in a context of ***,right-biased pigs were more sociable than left-biased ***,the present study indicates that personality is indeed related to lateralized cerebral processing and provides insight into the multifactorial nature of individuality.

关键词： approach-withdrawal hypothesis coping emotion hemispheric dominance motor lateralization temperament

Groundwater arsenic biogeochemistry-Key questions and use of tracers to understand arsenic-prone groundwater systems

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Geoscience Frontiers 2019年第5期10卷 1635-1641页

作者： David A. Polya charlotte Sparrenbom Saugata Datta Huaming Guo School of Earth and Environmental Sciences and Williamson Research Centre for molecular Environmental Science The University of ManchesterWilliamson BuildingOxford RoadManchesterM13 9PLUK Department of Geology Lund UniversityLundSweden Department of Geology Kansas State University108 Thompson HallManhattanKS66506-3201USA State Key Laboratory of Biogeology and Environmental Geology and School of Water Resources China University of GeosciencesBeijing 100083China

Over 100,000,000 people worldwide are exposed to high arsenic groundwater utilised for drinking or *** consequent global avoidable disease burden is estimated to be of the order of 100,000 avoidable deaths or more per annum from just direct exposures - *** indirect exposure (from rice and other foods) and excluding *** 1000s of papers published on arsenic (hydro)(bio)geochemistry,there remain a number of key outstanding questions to be addressed in relation to arsenic geoscience - these include questions related to:(i) the role of human activities - irrigation,agriculture and other land uses - on arsenic mobilisation in groundwaters;(ii) the specific sources,nature and role of organics,minerals and microbial communities involved in arsenic mobilisation;(iii) the relationship to microscopic to macroscopic scale geological (including tectonic) and evolution processes;(iv) unravelling the over-printing of multiple processes in complex highly heterogeneous aquifer systems and (v) using increasing understanding of the controls of arsenic mobility in groundwaters systems to informing improved locally-relevant remediation and mitigation *** article further summarises how the 9 further papers in this Special Issue address some of these questions through the use of chemical and/or isotopic tracers.

关键词： Arsenic Groundwater Biogeochemical cycles Tracers

Sedimentation in small-scale irrigation schemes in Ethiopia: Its sources and management

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International Journal of Sediment Research 2022年第5期37卷 576-588页

作者： Zerihun Anbesa Gurmu Henk Ritzema charlotte de Fraiture mekonen Ayana Water Resources management Group Wageningen University Arba minch University Department of Water Science and Engineering IHE Delft Institute for Water Education Adama Science and Technology University

Numerous irrigation schemes in sub-Saharan Africa(SSA) exhibit excessive sedimentation, resulting in underperformance and high maintenance costs. In the current study, a participatory monitoring program was used to investigate sediment causes and sources, measure the annual sediment load, and monitor desilting campaigns in two small scale irrigation schemes in Ethiopia, Arata-Chufa(100 ha) and Ketar(430 ha), for three years(2016-2018). Sedimentation quantities were huge, where the annual river sediment influx ranged from 220 m3for the Arata-Chufa scheme to 1,741 m3for the Ketar scheme. On average 0.3 m3/m of sediment were removed from the main canal for Arata-Chufa costing 794 days of labor per year. In Ketar, sediment quantities were even greater: 1.1 m3/m was removed requiring 3,118days of labor per year. The sediment influx from the river source amounts to up to 95% for Arata-Chufa and moderately reaches 46% for Ketar, with the remainder of the sediment entering with overland erosion flows. Farmers reported increased sedimentation over time and difficulty paying operation and maintenance fees instead preferring to contribute labor for the desilting campaigns. Sedimentation management is fragile and mainly involves frequent desilting campaigns and unharmonized efforts to reduce overland sediment inflows. Factors contributing to sediment deposition include mild longitudinal bed slopes, the location of the intake, canal layout, and lack of canal banks for protection against surface water inflow in addition to sub-optimal canal operations. Excessive sedimentation is a major challenge resulting in underperformance of numerous irrigation schemes in SSA, and the stakeholders’ lack of awareness of the sources of sedimentation is an underlying factor aggravating sedimentation problems. It is concluded that investigating the sources, extent, and types of sedimentation entering a small-scale irrigation scheme is the basis for reducing maintenance costs and for effective man

关键词： Sediment sources Sediment management Irrigation performance Soil loss River sediment Erosion

melting of carbonate wall rocks and formation of the heterogeneous aureole of the Panzhihua intrusion,China

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Geoscience Frontiers 2013年第5期4卷 535-546页

作者： Clement Ganino Nicholas T.Arndt Catherine Chauvel Alexandre Jean charlotte Athurion Geoazur Universite de Nice-Sophia AntipolisCNRS/IRD250 rue Albert Einstein06560 ValbonneFrance ISTerre Grenoble UniversitesCNRS/IRDBP 5338041 GrenobleCedex 9France

The Panzhihua gabbroic intrusion,part of the plumbing system of the Emeishan large igneous province, intruded late-Proterozoic dolomites and marls about～263 ma *** dolomites in the contact aureole were converted to brucite marbles and a diverse suite of forsterite,diopside and garnet *** variation in mineralogy is explained in part by differences in the composition of the protolith,particularly the proportion of silica minerals and clay,and in part by transfer of elements from intruding *** trace element compositions of most marbles and skarns are very similar to those of unmetamorphosed dolomites and marls,but some contain high Si,Ti,and Fe contents that are interpreted to have come from a magmatic *** brucite marbles sampled～10 m from the contact of the intrusion and named ＂enriched brucite marble＂ have trace element compositions very different from their dolomitic protolith：their rare earth elements are strongly enriched whereas levels of Nb-Ta,Zr-Hf and Ti are very *** characteristics resemble those of carbonate liquid in equilibrium with silicate liquid or more probably with silicate minerals in the case of Panzhihua,a similarity we take to indicate that the sample underwent partial *** taken up to 300 m from the contact contain brucite indicating that high temperatures persisted well into the country ***,other samples collected only tens of metres from the contact are only slightly recrystallized indicating that conditions in the aureole were highly *** suggest that temperatures within the aureole were controlled by conduction of heat from the main intrusion and by supply of additional heat from abundant small dykes within the *** of fluids derived from deeper levels in the aureole flushed the carbon dioxide from the dolomite,lowering temperature needed to partially melt carbonate to the temperatures attained near the *** but extensive heating destabilized the carbon

关键词： Panzhihua melting Carbonates Contact aureole Thermal metamorphism Petrology

A test of genetic association among male nuptial coloration, female mating preference, and male aggression bias within a polymorphic population of cichlid fish

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Current Zoology 2013年第2期59卷 221-229页

作者： Inke van der SLUIJS Peter D. DIJKSTRA charlotte m. LINDEYER BertanneVISSER Alan m. SmITH Ton G. G. GROOTHUIS Jacques J. m. van ALPHEN Ole SEEHAUSEN Department of Animal Ecology Institute of Biology Leiden University PO Box 9516 2300 RA Leiden The Netherlands The University of Texas at Austin Section of Integrative Biology 1 University Station-C0930 Austin TX 78712 United States Department of Biological Sciences University of Hull Cottingham Road Hull HU6 7RX United Kingdom Behavioural Biology Group University of Groningen P.O. Box 14 9750 AA Haren The Netherlands Institute of Zoology University of Bern Baltzerstrasse CH-3012 Bern Switzerland Eawag Swiss Federal Institute for Aquatic Science and Technology Centre of Ecology Evolution & Biogeochemistry Depart- ment ofFish Ecology & Evolution Seestrasse 97 6047 Kastanienbaum Switzerland

Both inter- and intrasexual selection have been implicated in the origin and maintenance of species-rich taxa with di- verse sexual traits. Simultaneous disruptive selection by female mate choice and male-male competition can, in theory, lead to ~,;peciation without geographical isolation if both act on the same male trait. Female mate choice can generate discontinuities in gene flow, while male-male competition can generate negative frequency-dependent selection stabilizing the male trait polymor- phism. Speciation may be facilitated when mating preference and/or aggression bias are physically linked to the trait they operate on. We tested for genetic associations among female mating preference, male aggression bias and male coloration in the Lake Victoria cichlid Pundamilia. We crossed females from a phenotypically variable population with males from both extreme ends of the phenotype distribution in the same population （blue or red）. male offspring of a red sire were significantly redder than males of a blue sire, indicating that intra-population variation in male coloration is heritable. We tested mating preferences of female offspring and aggression biases of male offspring using binary choice tests. There was no evidence for associations at the family level between female mating preferences and coloration of sires, but dam identity had a significant effect on female mate prefe- rence. Sons of the red sire directed significantly more aggression to red than blue males, whereas sons of the blue sire did not show any bias. There was a positive correlation among individuals between male aggression bias and body coloration, possibly due to pleiotropy or physical linkage, which could facilitate the maintenance of color polymorphism [Current Zoology 59 （2）： 221-229, 2013].

关键词： Disruptive selection Sexual selection Speciation Pundamilia Linkage disequilibrium

Simulation of size effects by a phase field model for fracture

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Theoretical & Applied mechanics Letters 2014年第5期4卷 50-53页

作者： charlotte Kuhn Ralf müller Computational mechanics University of Kaiserslautern67653 KaiserslauternGermany Institute of Applied mechanics University of Kaiserslautern67653 KaiserslauternGermany

In phase field fracture models the value of the order parameter distin- guishes between broken and undamaged material. At crack faces the order param- eter interpolates smoothly between these two states of the material, which can be regarded as phases. The crack evolution follows implicitly from the time inte- gration of an evolution equation of the order parameter, which is coupled to the mechanical field equations. Among other phenomena phase field fracture mod- els are able to reproduce crack nucleation in initially sound materials. For a 1D setting it has been shown that crack nucleation is triggered by the loss of stability of the unfractured, spatially homogeneous solution, and that the stability point depends on the size of the considered structure. This work numerically investi- gates to which extend size effects are reproduced by the 2D phase field model. Exemplarily, a finite element study of the hole size effect is performed and the simulation results are compared to exnerimental data.

关键词： phase field model fracture mechanics size effects stability finite elementmethod