bluuebunny/crossref_metadata_2025 huggingface dataset:
Allosteric modulation of the muscarinic M4receptor as an approach to treating schizophrenia
Authors: Chan W. Y. , McKinzie D. L. , Bose S. , Mitchell S. N. , Witkin J. M. , Thompson R. C. , Christopoulos A. , Lazareno S. , Birdsall N. J. M. , Bymaster F. P. , Felder C. C.
Published: August 2008

Current antipsychotics provide symptomatic relief for patients suffering from schizophrenia and related psychoses; however, their effectiveness is variable and many patients discontinue treatment due to side effects. Although the etiology of schizophrenia is still unclear, a leading hypothesis implicates an imbalanced dopaminergic system. Muscarinic acetylcholine (ACh) receptors regulate dopamine levels in key areas of the brain involved in psychosis, with the M4subtype emerging as a key regulator of dopaminergic hyperactivity. Unfortunately, no selective small molecule tools exist to provide pharmacological validation of this hypothesis. Here, we describe the discovery of a small molecule modulator, LY2033298, that is highly selective for human M4receptors by virtue of targeting an allosteric site on this receptor. Pharmacological assays confirmed the selectivity of LY2033298 for the M4receptor and revealed the highest degree of positive allosteric enhancement of ACh potency thus far identified. Radioligand binding assays also show this compound to directly potentiate agonist binding while having minimal effects on antagonist binding. Mutational analysis identified a key amino acid (D432) in the third extracellular loop of the human M4receptor to be critical for selectivity and agonist potentiation by LY2033298. Importantly, LY2033298 was active in animal models predictive of clinical antipsychotic drug efficacy indicating its potential use as a first-in-class, selective, allosteric muscarinic antipsychotic agent.
Mid-Miocene cooling and the extinction of tundra in continental Antarctica
Authors: Lewis Adam R. , Marchant David R. , Ashworth Allan C. , Hedenäs Lars , Hemming Sidney R. , Johnson Jesse V. , Leng Melanie J. , Machlus Malka L. , Newton Angela E. , Raine J. Ian , Willenbring Jane K. , Williams Mark , Wolfe Alexander P.
Published: August 2008

A major obstacle in understanding the evolution of Cenozoic climate has been the lack of well dated terrestrial evidence from high-latitude, glaciated regions. Here, we report the discovery of exceptionally well preserved fossils of lacustrine and terrestrial organisms from the McMurdo Dry Valleys sector of the Transantarctic Mountains for which we have established a precise radiometric chronology. The fossils, which include diatoms, palynomorphs, mosses, ostracodes, and insects, represent the last vestige of a tundra community that inhabited the mountains before stepped cooling that first brought a full polar climate to Antarctica. Paleoecological analyses,
40
Ar/
39
Ar analyses of associated ash fall, and climate inferences from glaciological modeling together suggest that mean summer temperatures in the region cooled by at least 8°C between 14.07 ± 0.05 Ma and 13.85 ± 0.03 Ma. These results provide novel constraints for the timing and amplitude of middle-Miocene cooling in Antarctica and reveal the ecological legacy of this global climate transition.
Hydraulic integration and shrub growth form linked across continental aridity gradients
Authors: Schenk H. Jochen , Espino Susana , Goedhart Christine M. , Nordenstahl Marisa , Cabrera Hugo I. Martinez , Jones Cynthia S.
Published: August 2008

Both engineered hydraulic systems and plant hydraulic systems are protected against failure by resistance, reparability, and redundancy. A basic rule of reliability engineering is that the level of independent redundancy should increase with increasing risk of fatal system failure. Here we show that hydraulic systems of plants function as predicted by this engineering rule. Hydraulic systems of shrubs sampled along two transcontinental aridity gradients changed with increasing aridity from highly integrated to independently redundant modular designs. Shrubs in humid environments tend to be hydraulically integrated, with single, round basal stems, whereas dryland shrubs typically have modular hydraulic systems and multiple, segmented basal stems. Modularity is achieved anatomically at the vessel-network scale or developmentally at the whole-plant scale through asymmetric secondary growth, which results in a semiclonal or clonal shrub growth form that appears to be ubiquitous in global deserts.
Four enzymes define the incorporation of coenzyme A in thienamycin biosynthesis
Authors: Freeman Michael F. , Moshos Kristos A. , Bodner Micah J. , Li Rongfeng , Townsend Craig A.
Published: August 2008

The enzymatic activities of three proteins encoded by the thienamycin gene cluster of
Streptomyces cattleya
(ThnR, ThnH, and ThnT) have been shown to incrementally cleave CoA to afford the active side-chain component of the β-lactam antibiotic thienamycin. These results supersede proposals based on earlier radiochemical incorporation experiments. For 20 years it has been thought that cysteine was directly incorporated into the antibiotic. Specific, stepwise truncation of CoA to 4-phosphopantetheine, pantetheine, and finally cysteamine was observed with ThnR, ThnH, and ThnT, respectively, in a series of coupled enzymatic assays. Pantetheinylated carbapenams were synthesized to address possible thienamycin biosynthetic intermediates and were shown to be effective substrates for the pantetheine-cleaving enzyme ThnT. Finally, a fourth gene,
thnF
, was shown to encode a protein capable of
N
-acetylating a model compound containing cysteamine in the presence of acetyl-CoA, consistent with the production of the
S. cattleya
cometabolite,
N
-acetylthienamycin. Taken together, these four enzymes are proposed to siphon CoA from primary metabolism to create the side chains for the predominant
S. cattleya
carbapenems, thienamycin and
N
-acetylthienamycin, in a process likely to be general for the broader class of these antibiotics.
Rapid protection in a monkeypox model by a single injection of a replication-deficient vaccinia virus
Authors: Earl Patricia L. , Americo Jeffrey L. , Wyatt Linda S. , Espenshade Ondraya , Bassler Jocelyn , Gong Kathy , Lin Shuling , Peters Elizabeth , Rhodes Lowrey , Spano Yvette Edghill , Silvera Peter M. , Moss Bernard
Published: August 2008

The success of the World Health Organization smallpox eradication program three decades ago resulted in termination of routine vaccination and consequent decline in population immunity. Despite concerns regarding the reintroduction of smallpox, there is little enthusiasm for large-scale redeployment of licensed live vaccinia virus vaccines because of medical contraindications and anticipated serious side effects. Therefore, highly attenuated strains such as modified vaccinia virus
Ankara
(MVA) are under evaluation in humans and animal models. Previous studies showed that priming and boosting with MVA provided protection for >2 years in a monkeypox virus challenge model. If variola virus were used as a biological weapon, however, the ability of a vaccine to quickly induce immunity would be essential. Here, we demonstrate more rapid immune responses after a single vaccination with MVA compared to the licensed Dryvax vaccine. To determine the kinetics of protection of the two vaccines, macaques were challenged intravenously with monkeypox virus at 4, 6, 10, and 30 days after immunization. At 6 or more days after vaccination with MVA or Dryvax, the monkeys were clinically protected (except for 1 of 16 animals vaccinated with MVA), although viral loads and number of skin lesions were generally higher in the MVA vaccinated group. With only 4 days between immunization and intravenous challenge, however, MVA still protected whereas Dryvax failed. Protection correlated with the more rapid immune response to MVA compared to Dryvax, which may be related to the higher dose of MVA that can be tolerated safely.
Activation of mitotic kinesin by microtubule bundling
Authors: Tomishige Michio
Published: August 2008

Kinesin-5 family members cross-link and slide parallel microtubules of opposite polarity, an activity that is essential for the formation of a bipolar spindle during mitosis. In this issue, Kapitein et al. (Kapitein, L.C., B.H. Kwok, J.S. Weinger, C.F. Schmidt, T.M. Kapoor, and E.J.G. Peterman. 2008. J. Cell Biol. 182:421–428) demonstrate that microtubule cross-linking triggers the conversion of kinesin-5 motility from a diffusive mode to a directional mode, initiating antiparallel microtubule sliding.
2-[4-(Diethylamino)phenyl]-1-ethylimidazo[4,5-f][1,10]phenanthroline. Corrigendum
Authors: Sun Min , Chen Guang , Wang Ke-Zhi
Published: August 2008

The list of authors in the paper by Sun, Chen, Ling & Liu [Acta Cryst. (2007), E63, o1210–o1211] is corrected.
N′-(4-Hydroxybenzylidene)-4-methoxybenzohydrazide
Authors: Bao Xia , Wei Yi-Jun
Published: August 2008

The title compound, C15H14N2O3, was prepared by the reaction of 4-hydroxybenzaldehyde and 4-methoxybenzohydrazide in methanol. The dihedral angle between the two benzene rings is 6.8 (1)°. The methoxy group is disordered over two orientations with occupancies of ca 0.63 and 0.37. In the major disorder component, the methoxy group is coplanar with the attached ring. In the crystal structure, the molecules are linked into a three-dimensional framework by intermolecular O—H...O and N—H...O hydrogen bonds.
A second monoclinic polymorph of 2-amino-4,6-dichloropyrimidine
Authors: Fun Hoong-Kun , Chantrapromma Suchada , Jana Subrata , Chakrabarty Rinku , Goswami Shyamaprosad
Published: August 2008

The title chloro-substituted 2-aminopyrimidine, C4H3Cl2N3, is a second monoclinic polymorph of this compound which crystallizes in the space group C2/c. The structure was previously reported [Clews & Cochran (1948). Acta Cryst. 1, 4–11] in the space group P21/a. There are two crystallographically independent molecules in the asymmetric unit and each molecule is planar. The dihedral angle between the two pyrimidine rings is 30.71 (12)°. In the crystal structure, molecules are linked via N—H...N intermolecular hydrogen bonds, forming infinite one-dimensional chains along the a axis. These hydrogen bonds generate R
2
2(8) ring motifs. The chains are stacked along the b axis.
3,5-Bis[1-acetyl-5-(4-chlorophenyl)-4,5-dihydro-1H-pyrazol-3-yl]-2,6-dimethylpyridine
Authors: Qian Qun , Zhang Jun , Zhang Min , He Xiang , Xia Yi-Ben
Published: August 2008

The title compound, C29H27Cl2N5O2, contains a central pyridine ring and two functionalized pyrazoline rings. The pyridine ring and the two attached pyrazoline rings are nearly coplanar, whereas the terminal chlorophenyl rings are nearly perpendicular to the attached pyrazoline rings [dihedral angles = 86.78 (1) and 77.70 (1)°]. Molecules are linked by weak intermolecular C—H...O hydrogen bonding.
(±)-trans-3-Benzoylbicyclo[2.2.2]octane-2-carboxylic acid
Authors: Lalancette Roger A. , Thompson Hugh W. , Brunskill Andrew P. J.
Published: August 2008

The title keto acid, C16H18O3, displays significant twisting of all three ethylene bridges in its bicyclo[2.2.2]octane structure owing to steric interactions; the bridgehead-to-bridgehead torsion angles are 13.14 (12), 13.14 (13) and 9.37 (13)°. The compound crystallizes as centrosymmetric carboxyl dimers [O...O = 2.6513 (12) Å and O—H...O = 178°], which have two orientations within the cell and contain no significant carboxyl disorder.
(RS)-N-[(4-Chlorophenyl)(phenyl)methyl]formamide
Authors: Zou Zhi-Hong , Wang Qi-Yuan , Li Zhong-Shu
Published: August 2008

The racemic title compound, C14H12ClNO, contains two molecules in the asymmetric unit. The dihedral angles between the phenyl and benzene rings are 84.03 (15) and 83.92 (13)°. The crystal structure involves intermolecular N—H...O, C—H...Cl and C—H...O hydrogen bonds, linking molecules into layers parallel to the (100) plane.
Redetermination of conichalcite, CaCu(AsO4)(OH)
Authors: Henderson Rachel R. , Yang Hexiong , Downs Robert T. , Jenkins Robert A.
Published: August 2008

The crystal structure of conichalcite [calcium copper(II) arsenate(V) hydroxide], with ideal formula CaCu(AsO4)(OH), was redetermined from a natural twinned specimen found in the Maria Catalina mine (Chile). In contrast to the previous refinement from photographic data [Qurashi & Barnes (1963). Can. Mineral.
7, 561–577], all atoms were refined with anisotropic displacement parameters and with the H atom located. Conichalcite belongs to the adelite mineral group. The Jahn–Teller-distorted [CuO6] octahedra share edges, forming chains running parallel to [010]. These chains are cross-linked by eight-coordinate Ca atoms and by sharing vertices with isolated AsO4 tetrahedra. Of five calcium arsenate minerals in the adelite group, the [MO6] (M = Cu, Zn, Co, Ni and Mg) octahedron in conichalcite is the most distorted, and the donor–acceptor O—H...O distance is the shortest.
Di-μ-bromido-bis[bromido(di-2-pyridylmethanediol-κ2
N,N′)copper(II)] dihydrate
Authors: Westcott Barry L. , Kopp-Vaughn Kristin M. , Daniels Lee M. , Zeller Matthias
Published: August 2008

The centrosymmetric title complex, [Cu2Br4(C11H10N2O2)2]·2H2O, was one of three complexes isolated by slow evaporation of an acetonitrile reaction mixture of CuBr2 with di-2-pyridyl ketone (1:1 molar ratio). The title complex contains a 1:1 metal-to-ligand ratio of copper(II) with the hydrated form of the ligand di-2-pyridylmethanediol. The copper centers are bridged by bromide donors, leading to a Cu—Cu distance of 4.090 (6) Å. The crystals form as non-merohedral twins with two components related by a 180° rotation around the normal to [100]; the selected sample had a twin ratio of 0.63:0.37.
(E)-Methyl N′-[1-(4-hydroxyphenyl)ethylidene]hydrazinecarboxylate
Authors: Lv Lu-Ping , Xie Jian-Wu , Yu Wen-Bo , Li Wei-Wei , Hu Xian-Chao
Published: August 2008

The title compound, C10H12N2O3, adopts a trans configuration with respect to the C=N bond. The dihedral angle between the benzene ring and the hydrazine carboxylic acid plane is 8.29 (7)°. Molecules are linked into a three-dimensional network by N—H...O, O—H...O, O—H...N hydrogen bonds and C—H...π interactions.
Bis(2,2′-bipyridine-κ2
N,N′)(4-methylbenzoato-κ2
O,O′)copper(II) iodide hemihydrate
Authors: Tang Chuan-Mei , Deng Guo-Hua
Published: August 2008

The title compound, [Cu(C8H7O2)(C10H8N2)2]I·0.5H2O, was obtained by the hydrothermal reaction of copper(I) iodide, 4-methylbenzoic acid and 2,2′-bipyridine. The initial reactant of CuI was oxidized to CuII. The asymmetric unit contains two independent complex molecules, two I− ions and one water molecule. Each CuII atom is coordinated by two O atoms from a 4-methylbenzoate ligand and four N atoms from two 2,2′-bipyridine ligands, displaying a distorted octahedral geometry. The structure involves O—H...I hydrogen bonds between the water molecule and iodide ions and π–π stacking interactions between the benzene and pyridyl rings [centroid–centroid distance = 3.79 (1) Å] and between the pyridyl rings [centroid–centroid distance = 3.87 (1) Å].
3-Methylsulfinyl-2-phenyl-1-benzofuran
Authors: Choi Hong Dae , Seo Pil Ja , Son Byeng Wha , Lee Uk
Published: August 2008

The title compound, C15H12O2S, was prepared by the oxidation of 3-methylsulfanyl-2-phenyl-1-benzofuran with 3-chloroperoxybenzoic acid. The phenyl ring makes a dihedral angle of 37.65 (8)° with the plane of the benzofuran fragment. The O atom and the methyl group of the methylsulfinyl substituent lie on opposite sides of the plane of the benzofuran ring system. The crystal structure is stabilized by aromatic π–π interactions between the benzene rings of neighbouring molecules [centroid–centroid distance = 3.549 (2) Å] and by intermolecular C—H...O interactions.
catena-Poly[[[diaquacopper(II)]-{μ-4,4′-[1,4-phenylenebis(methyleneimino)]dibenzoato}] monohydrate]
Authors: Wang Qiu-sheng , Ouyang Jie
Published: August 2008

The asymmetric unit of the title polymeric compound, {[Cu(C22H18N2O4)(H2O)2]·H2O}
n
, contains a Cu ion situated on an inversion center, half of a centrosymmetric 4,4′-[1,4-phenylenebis(methyleneimino)]dibenzoate ligand, a coordinated water molecule in a general position and an uncoordinated water molecule situated on a twofold rotation axis. The distorted octahedral coordination geometry of the CuII ion is formed by six O atoms. The –NH– groups of the ligand are involved in intramolecular N—H...O hydrogen bonds, while the water molecules participate in the formation of a three-dimensional supramolecular framework via intermolecular O—H...O hydrogen bonds.
1,5-Dimethyl-4-[(E)-3-phenoxybenzylideneamino]-2-phenyl-1H-pyrazol-3(2H)-one
Authors: Sun Yi-Feng , Zhang Feng-Yu , Liu Yang , Wang Zi-Ying , Cheng Xue-Li
Published: August 2008

The title Schiff base, C24H21N3O2, adopts an E configuration with respect to the central C=N bond. The pyrazole ring and the central benzene ring attached to the imino group are almost coplanar. The phenyl ring attached to the pyrazole unit is twisted by 39.3 (2)° with respect to the pyrazole ring plane. The phenoxy benzene ring makes a dihedral angle of 79.8 (2)° with the central benzene ring.
Aquabis(3′-hydroxy-2,2′-bipyridine-3-olato-κ2
N,N′)zinc(II)
Authors: Zhang Shi Guo , Hou Chao
Published: August 2008

In the title complex, [Zn(C10H7N2O2)2(H2O)], the ZnII ion and water O atom are located on a crystallographic twofold rotation axis and the metal atom assumes a distorted trigonal-bipyramidal ZnN4O coordination geometry. An intramolecular O—H...O hydrogen bond occurs within the ligand and intermolecular O—H...O hydrogen bonds involving the water molecule result in a sheet structure in the crystal structure. In addition, a short C—O...π contact between the O atom of the deprotonated hydroxyl group and a nearby pyridine ring [O...Cg = 3.977 (2) Å, where Cg is the centroid of the pyridine ring] is observed.
2,2′-Dimethyl-7,7′-(methylenediimino)di-1,8-naphthyridin-1-ium bis(perchlorate)
Authors: Mo Juan , Liu Jian-Hua , Pan Yu-Shan , Zhang Su-Mei , Du Xiang-Dang
Published: August 2008

In the title salt, C19H20N6
2+·2ClO4
−, the two planar 1,8-naphthyridine systems are linked by a methylenediamine group with a dihedral angle of 60.6 (1)° between the two systems. The crystal structure involves extensive N—H...O and C—H...O hydrogen bonding.
2-{3-Cyano-5,5-dimethyl-4-[4-(pyrrolidin-1-yl)buta-1,3-dienyl]-2,5-dihydrofuran-2-ylidene}malononitrile dichloromethane solvate
Authors: Gainsford Graeme J. , Bhuiyan M. Delower H. , Kay Andrew J. , Robinson Ward T.
Published: August 2008

The structure of the title compound, C18H18N4O·CH2Cl2, was solved using data collected from a multiple crystal (note high R factors). The crystal structure is dominated by two bifurcated attractive C—H...N(cyano) interactions.
Non‐interactive effects of habitat complexity and adult crayfish on survival and growth of juvenile crayfish (Pacifastacus leniusculus)
Authors: OLSSON KARIN , NYSTRÖM PER
Published: August 2008

1. In a 1‐month outdoor stream channel experiment, we investigated the relative importance of habitat complexity (i.e. cobbled area) and the presence of adult signal crayfish (Pacifastacus leniusculus) males on the survival and growth of juveniles.

2. In treatments with high habitat complexity, more juveniles survived, more were newly moulted and they had a higher specific growth rate (SGR) at the end of the experiment than juveniles in treatments with low habitat complexity. The presence of adult males did not affect survival, moulting stage or growth of the juveniles.

3. The presence of adult males decreased juvenile activity during night. Juveniles in treatments with low habitat complexity were more active than juveniles in high habitat complexity during both day and night.

4. There was no difference in total invertebrate biomass between treatments. However, some invertebrate taxa, such as Chironomidae larvae, were affected by habitat complexity or the presence of adult crayfish. Juvenile crayfish in all channels had consumed detritus, algae and Chironomidae larvae and there were no differences in gut contents or stable isotope signals (carbon and nitrogen) between treatments, indicating a similar diet among the juveniles across treatments. However, the biomass of chironomids was significantly higher in channels with adult crayfish present, indicating a decreased consumption of chironomids by juveniles in the presence of adults.

5. Our results suggest that the recruitment of juvenile crayfish is mostly affected by habitat complexity. The competition for food and shelter and aggressive interactions between the juveniles were most pronounced in low habitat complexity, indicating that habitats with a good access to shelter will enhance recruitment of juvenile crayfish in streams.
Safety update on the use of recombinant factor VIIa and the treatment of congenital and acquired deficiency of factor VIII or IX with inhibitors
Authors: ABSHIRE T. , KENET G.
Published: August 2008

Summary.  Recombinant factor VIIa (rFVIIa, NovoSeven®) has been licensed for treatment of haemophilia with inhibitors in Europe since 1996 and in North America since 1999. Overall, approximately 1.5 million doses have since been administered. Safety data from licensure to April 2003 revealed 25 thromboembolic (TE) adverse events (AE) from over 700 000 doses given, a remarkably low incidence of TE events. Recent reports have cited a higher prevalence of TE events with rFVIIa use, especially when used off‐label. This report reviews the TE and fatal events with use of rFVIIa for congenital and acquired haemophilia A or B from May 2003 to December 2006. Approximately 800 000 standard doses of rFVIIa have been administered during this time frame. All clinical trials, spontaneous and solicited reports, as well as a detailed literature review, were included in the data analysis. There were a total of 30 TE events and 6 TE‐associated fatal events. Spontaneous reports captured 14/71 (20%) TE/AE and 2/34 TE‐associated/total fatal events. From solicited reports, 5/40 (12.5%) were associated with a TE and 1/32 TE‐associated fatal events. Literature review revealed 11/19 (58%) TE events and 3/6 TE‐associated fatal events. Despite the use of high‐dose rFVIIa (270 μg kg−1) in some clinical trials and registries, rFVIIa appears safe, when used for congenital and acquired haemophilia. The prevalence of TE associated with rFVIIa use is less than 4/100 000 and a TE‐associated fatal event is also extremely rare. However, use of rFVIIa for off‐label indications should continue to be monitored closely via clinical trials and carefully designed registries.
A survey of adherence to haemophilia therapy in six European countries: results and recommendations
Authors: DE MOERLOOSE P. , URBANCIK W. , VAN DEN BERG H. M. , RICHARDS M.
Published: August 2008

Summary.  Very few studies have addressed the question of adherence of haemophiliacs to their treatment. The aim of our study was to compare their levels of adherence to therapy and also to provide recommendations. Professionals of an international research company performed individual interviews with 30 patients in each of six European countries (France, Germany, Italy, Spain, Sweden and UK) resulting in a total of 180 patients. Twenty‐eight interviews with haemophilia physicians and specialist nurses were also undertaken. Overall adherence to treatment was high (80–87% in each country). There was a positive correlation between greater adherence and younger age, prophylactic treatment, time spent with a haemophilia treatment centre (HTC) and the quality of the relationship with the haematologist and nurse. The four leading reasons for not using the prescribed amount of clotting factor or skipping the administration interval were reduction, fluctuation or disappearance of symptoms, forgetfulness, lack of time for treatment and convenience. These reasons differed according to the country and the age of the patient. The main suggestions made by patients to improve adherence related to HTC, environment and factor concentrates. Patients considered also that internet and electronic patient diaries were likely to improve adherence. In this selected group of European haemophilia patients, adherence to treatment appears higher than for most patients with other chronic diseases. However, it remains important to be aware of the possibility of non‐adherence given the serious implications, particularly when considering a differently selected group of patients.
Distinctiveness in the face of gene flow: hybridization between specialist and generalist gartersnakes
Authors: FITZPATRICK BENJAMIN M. , PLACYK, JR JOHN S. , NIEMILLER MATTHEW L. , CASPER GARY S. , BURGHARDT GORDON M.
Published: August 2008

Patterns of divergence and polymorphism across hybrid zones can provide important clues as to their origin and maintenance. Unimodal hybrid zones or hybrid swarms are composed predominantly of recombinant individuals whose genomes are patchworks of alleles derived from each parental lineage. In contrast, bimodal hybrid zones contain few identifiable hybrids; most individuals fall within distinct genetic clusters. Distinguishing between hybrid swarms and bimodal hybrid zones can be important for taxonomic and conservation decisions regarding the status and value of hybrid populations. In addition, the causes of bimodality are important in understanding the generation and maintenance of biological diversity. For example, are distinct clusters mostly reproductively isolated and co‐adapted gene complexes, or can distinctiveness be maintained by a few ‘genomic islands’ despite rampant gene flow across much of the genome? Here we focus on three patterns of distinctiveness in the face of gene flow between gartersnake taxa in the Great Lakes region of North America. Bimodality, the persistence of distinct clusters of genotypes, requires strong barriers to gene flow and supports recognition of distinct specialist (Thamnophis butleri) and generalist (Thamnophis radix) taxa. Concordance of DNA‐based clusters with morphometrics supports the hypothesis that trophic morphology is a key component of divergence. Finally, disparity in the level of differentiation across molecular markers (amplified fragment length polymorphisms) indicates that distinctiveness is maintained by strong selection on a few traits despite high gene flow currently or in the recent past.
Globally panmictic population structure in the opportunistic fungal pathogen Aspergillus sydowii
Authors: RYPIEN KRYSTAL L , ANDRAS JASON P , HARVELL C. DREW
Published: August 2008

Recent outbreaks of new diseases in many ecosystems are caused by novel pathogens, impaired host immunity, or changing environmental conditions. Identifying the source of emergent pathogens is critical for mitigating the impacts of diseases, and understanding the cause of their recent appearances. One ecosystem suffering outbreaks of disease in the past decades is coral reefs, where pathogens such as the fungus Aspergillus sydowii have caused catastrophic population declines in their hosts. Aspergillosis is one of the best‐characterized coral diseases, yet the origin of this typically terrestrial fungus in marine systems remains unknown. We examined the genetic structure of a global sample of A. sydowii, including isolates from diseased corals, diseased humans, and environmental sources. Twelve microsatellite markers reveal a pattern of global panmixia among the fungal isolates. A single origin of the pathogen into marine systems seems unlikely given the lack of isolation by distance and lack of evidence for a recent bottleneck. A neighbour‐joining phylogeny shows that sea fan isolates are interspersed with environmental isolates, suggesting there have been multiple introductions from land into the ocean. Overall, our results underscore that A. sydowii is a true opportunist, with a diversity of nonrelated isolates able to cause disease in corals. This study highlights the challenge in distinguishing between the role of environment in allowing opportunistic pathogens to increase and actual introductions of new pathogenic microorganisms for coral diseases.
Mechano‐perception in Chara cells: the influence of salinity and calcium on touch‐activated receptor potentials, action potentials and ion transport
Authors: SHEPHERD VIRGINIA A. , BEILBY MARY J. , AL KHAZAALY SABAH A.S. , SHIMMEN TERUO
Published: August 2008

This paper investigates the impact of increased salinity on touch‐induced receptor and action potentials of Chara internodal cells. We resolved underlying changes in ion transport by current/voltage analysis. In a saline medium with a low Ca2+ ion concentration [(Ca2+)ext], the cell background conductance significantly increased and proton pump currents declined to negligible levels, depolarizing the membrane potential difference (PD) to the excitation threshold [action potential (AP)threshold]. The onset of spontaneous repetitive action potentials further depolarized the PD, activating K+ outward rectifying (KOR) channels. K+ efflux was then sustained and irrevocable, and cells were desensitized to touch. However, when [Ca2+]ext was high, the background conductance increased to a lesser extent and proton pump currents were stimulated, establishing a PD narrowly negative to APthreshold. Cells did not spontaneously fire, but became hypersensitive to touch. Even slight touch stimulus induced an action potential and further repetitive firing. The duration of each excitation was extended when [Ca2+]ext was low. Cell viability was prolonged in the absence of touch stimulus. Chara cells eventually depolarize and die in the saline media, but touch‐stimulated and spontaneous excitation accelerates the process in a Ca2+‐dependent manner. Our results have broad implications for understanding the interactions between mechano‐perception and salinity stress in plants.
Oxygen isotope composition of CAM and C3Clusia species: non‐steady‐state dynamics control leaf water 18O enrichment in succulent leaves
Authors: CERNUSAK LUCAS A. , MEJIA‐CHANG MONICA , WINTER KLAUS , GRIFFITHS HOWARD
Published: August 2008

Leaf gas exchange and leaf water 18O enrichment (Δ18OL) were measured in three Clusia species under field conditions during dry and wet seasons and in Miconia argentea during the dry season in the Republic of Panama. During the dry season, all three Clusia species used crassulacean acid metabolism (CAM); during the wet season Clusia pratensis operated in the C3 mode, while Clusia uvitana and Clusia rosea used CAM. Large departures from isotopic steady state were observed in daytime Δ18OL of the Clusia species, especially during the dry season. In contrast, daytime Δ18OL was near isotopic steady state in the C3 tree M. argentea. Across the full data set, non‐steady‐state predictions explained 49% of variation in observed Δ18OL, whereas steady‐state predictions explained only 14%. During the wet season, when Δ18OL could be compared with Clusia individuals operating in both C3 and CAM modes, steady‐state and non‐steady‐state models gave contrasting predictions with respect to interspecific variation in daytime Δ18OL. The observed Δ18OL pattern matched that predicted for the non‐steady state. The results provided a clear example of how non‐steady‐state control of leaf water 18O dynamics can shift the slope of the relationship between transpiration rate and daytime Δ18OL from negative to positive.
Fine‐root respiration in a loblolly pine (Pinus taeda L.) forest exposed to elevated CO2 and N fertilization
Authors: DRAKE JOHN E. , STOY PAUL C. , JACKSON ROBERT B. , DeLUCIA EVAN H.
Published: August 2008

Forest ecosystems release large amounts of carbon to the atmosphere from fine‐root respiration (Rr), but the control of this flux and its temperature sensitivity (Q10) are poorly understood. We attempted to: (1) identify the factors limiting this flux using additions of glucose and an electron transport uncoupler (carbonyl cyanide m‐chlorophenylhydrazone); and (2) improve yearly estimates of Rr by directly measuring its Q10in situ using temperature‐controlled cuvettes buried around intact, attached roots. The proximal limits of Rr of loblolly pine (Pinus taeda L.) trees exposed to free‐air CO2 enrichment (FACE) and N fertilization were seasonally variable; enzyme capacity limited Rr in the winter, and a combination of substrate supply and adenylate availability limited Rr in summer months. The limiting factors of Rr were not affected by elevated CO2 or N fertilization. Elevated CO2 increased annual stand‐level Rr by 34% whereas the combination of elevated CO2 and N fertilization reduced Rr by 40%. Measurements of in situ Rr with high temporal resolution detected diel patterns that were correlated with canopy photosynthesis with a lag of 1 d or less as measured by eddy covariance, indicating a dynamic link between canopy photosynthesis and root respiration. These results suggest that Rr is coupled to daily canopy photosynthesis and increases with carbon allocation below ground.
Gene expression analysis in citrus reveals the role of gibberellins on photosynthesis and stress
Authors: HUERTA LAURA , FORMENT JAVIER , GADEA JOSÉ , FAGOAGA CARMEN , PEÑA LEANDRO , PÉREZ‐AMADOR MIGUEL A. , GARCÍA‐MARTÍNEZ JOSÉ LUIS
Published: August 2008

The effect of gibberellins (GA) on internode transcriptome was investigated in transgenic Carrizo citrange (Citrus sinensis × Poncirus trifoliata) plants overexpressing endogenousCcGA20ox1(encoding a GA biosynthetic gene), and in non‐transformed explants treated with GA3, using a citrus cDNA microarray. Substantial modulation of gene expression was found in senseCcGA20oxplants. Extensive up‐regulation of genes involved in photosynthesis and carbon utilization, and down‐regulation of those involved in protein synthesis and ribosome biogenesis were shown for the first time in plants with higher GA content. Importantly, increase of net photosynthesis in attached leaves was also demonstrated. Expression of other genes belonging to functional groups not reported previously to be regulated by GA (mainly abiotic and biotic stresses, and cuticle biosynthesis), and genes involved in cell division and cell wall architecture were also differentially expressed. Culture of citrus explants for 24 h in GA3solution produced much lower changes in the transcriptome compared withCcGA20oxplants (1.6% versus 16%, respectively, of total genes in the microarray), suggesting that most of the changes observed inCcGA20oxplants were a consequence of a long‐standing GA effect. Interestingly, genes related to abiotic and biotic stresses were similarly modulated in transgenics and GA3‐treated explants.
MAP‐kinase‐activated protein kinase 2 expression and activity is induced after neuronal depolarization
Authors: Thomas Tobias , Hitti Edward , Kotlyarov Alexey , Potschka Heidrun , Gaestel Matthias
Published: August 2008

Mitogen‐activated protein kinase‐activated protein kinase (MK)2 is one of several downstream targets of p38 mitogen‐activated protein kinase and has a well documented role in inflammation. Here, we describe a possible new function of MK2. We show that triggering depolarization by potassium chloride or increasing the cellular cAMP by forskolin treatment led to elevated levels of expression and activity of mouse MK2. In both treatments, the kinase inhibitor H89 completely prevented the up‐regulation of MK2 at the transcript level. By the use of different cell lines we demonstrated that the induction of MK2 expression is characteristic of neuronal cells and is absent in fibroblasts, macrophages and kidney cells. In vivo, induction of a status epilepticus by systemic administration of the chemoconvulsant kainic acid resulted in markedly reduced neurodegeneration in the pyramidal layer of the hippocampus, dentate gyrus and hilus of MK2‐deficient mice compared with wild‐type mice. Together, our data suggest a possible role of MK2 in the cellular response after neuronal depolarization, in particular in excitotoxicity.
The effects of rod and cone loss on the photic regulation of locomotor activity and heart rate
Authors: Thompson Stewart , Lupi Daniela , Hankins Mark W. , Peirson Stuart N. , Foster Russell G.
Published: August 2008

Behavioral responses to light indirectly affect cardiovascular output, but in anesthetized rodents a direct effect of light on heart rate has also been described. Both the basis for this response and the contribution of rods, cones and melanopsin‐based photosensitive retinal ganglion cells (pRGCs) remains unknown. To understand how light acutely regulates heart rate we studied responses to light in mice lacking all rod and cone photoreceptors (rd/rd cl ) along with wild‐type controls. Our initial experiments delivered light to anesthetized mice at Zeitgeber time (ZT)16 (4 h after lights off, mid‐activity phase) and produced an increase in heart rate in wild‐type mice, but not in rd/rd cl animals. By contrast, parallel experiments in freely‐moving mice demonstrated that light exposure at this time suppressed heart rate and activity in both genotypes. Because of the effects of anesthesia, all subsequent studies were conducted in freely‐moving animals. The effects of light were also assessed at ZT6 (mid‐rest phase). At this timepoint, wild‐type mice showed an irradiance‐dependent increase in heart rate and activity. By contrast, rd/rd cl mice failed to show any modulation of heart rate or activity, even at very high irradiances. Increases in heart rate preceded increases in locomotor activity and remained elevated when locomotor activity ceased, suggesting that these two responses are at least partially uncoupled. Collectively, our results show an acute and phase‐dependent effect of light on cardiovascular output in mice. Surprisingly, this irradiance detection response is dependent upon rod and cone photoreceptors, with no apparent contribution from melanopsin pRGCs.
Single‐port laparoscopy in colorectal surgery
Authors: Remzi F. H. , Kirat H. T. , Kaouk J. H. , Geisler D. P.
Published: August 2008

Purpose  Laparoscopy is the approach of choice for the majority of colorectal disorders that require a minimally invasive abdominal operation. As the emphasis on minimizing the technique continues, natural orifice surgery is quickly evolving. The authors utilized an embryologic natural orifice, the umbilicus, as sole access to the abdomen to perform a colorectal procedure. Herein, we present our initial experience of single‐port laparoscopic colorectal surgery using a Uni‐X™ Single‐Port Access Laparoscopic System (Pnavel Systems, Morganville, New Jersey, USA) with a multi‐channel cannula and specially designed curved laparoscopic instrumentation.

Method  The abdomen was approached through a 3.5 cm incision via the umbilicus and a single‐port access device was utilized to perform a right hemicolectomy on a patient with an unresectable caecal polyp and a body mass index of 35. Ligation of the ileocolic artery was done with a LigaSure Device™ (Covidien Ltd, Norwalk, Connecticut, USA), and was followed by colonic mobilization, extraction and extracorporeal ileocolic anastomosis.

Results  The total operative time was 115 min with minimal blood loss. Hospital stay was 4 days with no undue sequelae.

Conclusion  Single‐port laparoscopic surgery may allow common colorectal laparoscopic operations to be performed entirely through the patient’s umbilicus and enable an essentially scarless procedure. Additional experience and continued investigation are warranted.
Variance inflation in sequential calculations of body surface area, plasma volume, and prostate‐specific antigen mass
Authors: Sivanandam Arun , Siva Siddharth , Bhandari Mahendra , Menon Mani
Published: August 2008

OBJECTIVE

To assess the magnitude of variability among 11 formulae for human body surface area (BSA) and then among eight for plasma volume (PV), as used to represent physiological indices for body metabolism, drug dosages and body fluid management, and to evaluate the potential cumulative effect of variance inflation with prostate‐specific antigen (PSA) mass as an endpoint.

PATIENTS AND METHODS

In 3020 men undergoing robotic radical prostatectomy (RRP) at the Vattikuti Urology Institute between 2001 and 2008, the variation in BSA and PV formulae was calculated, as well as PSA mass, using analysis of variance (anova), Bland‐Altman plots, linear regression, and correlation analyses.

RESULTS

For estimating BSA,anovaindicated significant variance among the 11 formulae used (P < 0.001) with a between‐groups variance of 5.45. Bland‐Altman plots reported bias when the Dubois formula was compared to other BSA formulae. Furthermore theanovafor PV, with BSA as a predictor, indicated significant variance among the eight formulae used (P < 0.001), with a mean between‐group variance of 444.4 and a mean inflation factor of 81.5. Scatter plots between one PV formula (Boer) and others had a good linear fit. For PSA mass,anovaindicated significant variance (P < 0.001) using PV as a predictor, with a mean between‐group variance of 16 799.6 and a mean variance inflation factor of 37.8.

CONCLUSIONS

There is significant variation in the BSA calculated by commonly used formulae. This variation is carried over and further magnified in the sequential calculation of PV and PSA mass. Hence arbitrary selection of BSA and PV formulae is likely to affect inferences.
THE NEUTRALITY OF RIGHTNESS AND THE INDEXICALITY OF GOODNESS: BEYOND OBJECTIVITY AND BACK AGAIN
Authors: Fileva Iskra
Published: August 2008

My purpose in the present paper is two‐fold: to provide a theoretical framework for understanding the difference between rightness and virtue; and to systematically account for the role of objective rightness in an individual person's decision making. I argue that a decision to do something virtuous differs from a decision to do what's right not simply, as is often supposed, in being motivated differently but, rather, in being taken from a different point of view. My argument to that effect is the following. The ‘objectively right’ course of action must be right, ‘neutrally’ speaking, that is right for each of the participants in a given situation: if it is right for you to do A, then it cannot, at the same time, be right for me to prevent you from doing A. But the latter is precisely how things work with virtuous action: for instance, it may be virtuous of you to assume responsibility for my blunder, but it isn't virtuous of me to let you do so. I maintain, on this basis, that, while objectivity does have normative force in moral decision‐making, the objective viewpoint is not, typically, the viewpoint from which decisions to act virtuously are taken. I then offer an account of objectivity's constraining power.
Citizenship in the Faroe Islands: Participant, Parochial or Colonial?
Authors: Hoff Jens , West Hallbera Fríða
Published: August 2008

This article analyses citizenship and political culture in the Faroe Islands based on a quantitative survey carried out in summer 2004. Located theoretically in the tradition of Scandinavian citizenship investigations and its predecessors in the ‘civic culture’ tradition of Almond and Verba, four areas of citizenship are analysed: political engagement, democratic participation, political efficacy and democratic identity. The main hypothesis is that the character of citizenship in the Faroe Islands is very similar to that found in the Scandinavian countries in general. While most of the results found confirm this hypothesis, there are a number of special features that demand alternative explanations. Thus, the fact that the Faroese score much below the Scandinavian average concerning ‘postmodern’ forms of political participation like political consumption or boycott of goods, and that gender differences are bigger than in other Scandinavian countries when it comes to female representation in the Faroese parliament and in government, seems better explained by the relative remoteness of the islands from the Scandinavian political and cultural mainstream (the parochialism hypothesis). Also the fact that the Faroese are much less confident in speaking at public meetings, sending letters to newspapers or complaining to authorities than, for example, Danes in general calls for an alternative explanation. As these features go together with much less knowledge about and confidence in the Danish parliament (‘Folketinget’) and a lower level of efficacy towards the parliament than among Danes in general, the most likely explanation seem to be found in the way in which Danish supremacy has affected political culture in the Faroe Islands (the colonialism hypothesis).
Students’ learning experiences from interprofessional collaboration on a training ward in municipal care
Authors: Lidskog Marie , Löfmark Anna , Ahlström Gerd
Published: August 2008

One way to offer students pursuing health and social care programmes realistic experiences of teamwork is interprofessional training wards where students from different educational programmes learn teamwork by working together. In the present study, a training ward in municipal care for older people was evaluated. Students from occupational therapy, nursing and social work programmes worked together on the ward for 3 weeks to learn with, from and about each other. The aim of the study was to compare students’ attitudes towards practice on a training ward before and after and to evaluate goal fulfilment after 3 weeks’ interprofessional education on a training ward. An attitude questionnaire was distributed to all students before and after their time on the ward, supplemented with a retrospective goal‐fulfilment questionnaire afterwards. The results show that the collaborative, social experience the training ward offers was appreciated by the students and in most respects, met the learning goals set up for the course. The most important learning experience was working together in a real‐life setting. However, there are some issues to take into consideration when planning and developing training wards. The setting needs to be realistic and relevant in relation to future roles for all of the student groups involved. The value and purpose of engaging together in basic patient care needs to be the subject of further investigation. When it comes to fostering competent team‐workers, training wards seem to be one way forward. But to fully understand the challenges and difficulties involved in planning these wards, the learning achieved must be understood in the context of the setting as a whole, in all its aspects.
Examining access to GP services in rural Ireland using microsimulation analysis
Authors: Morrissey Karyn , Clarke Graham , Ballas Dimitris , Hynes Stephen , O'Donoghue Cathal
Published: August 2008

This paper analyses the effect accessibility has on General Practitioner (GP) utilisation rates at the sub‐national level for Ireland. Specifically, the aim of this paper is to estimate whether there is an urban–rural differential in GP utilisation rates. We do this by simulating micro‐level healthcare data. Using this synthetic data, simple logit models are employed to estimate the likelihood that individuals in different jurisdictions will attend a GP surgery. These individual logit estimates are then inputted into a spatial interaction model to highlight areas with low GP accessibility given their health status. The policy implications of these results are discussed in relation to both the healthcare literature and current Irish healthcare policy.