bluuebunny/crossref_metadata_2025 huggingface dataset:
VEGF‐Mediated Elevated Intracellular Calcium and Angiogenesis in Human Microvascular Endothelial Cells In Vitro are Inhibited by Dominant Negative TRPC6
Authors: ZADEH M.A. HAMDOLLAH , GLASS CATHERINE A. , MAGNUSSEN ANETTE , HANCOX JULES C. , BATES DAVID O.
Published: September 2008

Objective: Vascular endothelial growth factor (VEGF)‐induced vascular permeability has been shown to be dependent on calcium influx, possibly through a transient receptor potential cation channel (TRPC)‐mediated cation channel with properties of the TRPC3/6/7 subfamily. To investigate further the involvement of this subfamily, we determined the effects of dominant negative TRPC6 overexpression on VEGF‐mediated changes of human microvascular endothelial cell (HMVEC) calcium, proliferation, migration, and sprouting. Methods: Cytoplasmic calcium concentration was estimated by fura‐2 fluorescence spectrophotometry, migration by Boyden chamber assay, sprouting by immunofluorescence imaging of stimulated endothelial cells, and proliferation by flow cytometry. Results: Overexpression of a dominant negative TRPC6 construct in HMVECs inhibited the VEGF‐mediated increases in cytosolic calcium, migration, sprouting, and proliferation. In contrast, overexpression of a wild‐type TRPC6 construct increased the proliferation and migration of HMVECs. Conclusions: TRPC6 is an obligatory component of cation channels required for the VEGF‐mediated increase in cytosolic calcium and subsequent downstream signaling that leads to processes associated with angiogenesis.
cAMP-mediated Induction of Cyclin E Sensitizes Growth-arrested Adipose Stem Cells to DNA Damage–induced Apoptosis
Authors: Ugland Hege , Boquest Andrew C. , Naderi Soheil , Collas Philippe , Blomhoff Heidi Kiil
Published: September 2008

The differentiation capacity of mesenchymal stem cells has been extensively studied, but little is known on cell cycle–related events in the proliferation and differentiation phases of these cells. Here, we demonstrate that exposure to cAMP-increasing agents inhibits proliferation of adipose stem cells (ASCs). This antiproliferative effect is associated with both reduced cdk2 activity and pRB phosphorylation. Concomitantly, however, the level of cyclin E markedly increases upon cAMP induction, indicating that cyclin E may have cdk2-independent functions in these cells besides its role as a cdk2 activator. Indeed, we found indications of a cdk2-independent role of cyclin E in DNA damage–induced apoptosis. 8-CPT-cAMP sensitizes ASCs to γ-irradiation–induced apoptosis, an effect abolished by knockdown of cyclin E. Moreover, cAMP induces early activation of ERK, leading to reduced degradation of cyclin E. The cAMP-mediated up-regulation of cyclin E was blocked by knockdown of ERK or by an inhibitor of the ERK kinase MEK. We conclude that cAMP inhibits cdk2 activity and pRB phosphorylation, leading to reduced ASC proliferation. Concomitant with this growth inhibition, however, cyclin E levels are increased in a MEK/ERK-dependent manner. Our results suggest that cyclin E plays an important, cdk2-independent role in genotoxic stress–induced apoptosis in mesenchymal stem cells.
Wounding Sheets of Epithelial Cells Activates the Epidermal Growth Factor Receptor through Distinct Short- and Long-Range Mechanisms
Authors: Block Ethan R. , Klarlund Jes K.
Published: September 2008

Wounding epithelia induces activation of the epidermal growth factor receptor (EGFR), which is absolutely required for induction of motility. ATP is released from cells after wounding; it binds to purinergic receptors on the cell surface, and the EGFR is subsequently activated. Exogenous ATP activates phospholipase D, and we show here that ATP activates the EGFR through the phospholipase D2 isoform. The EGFR is activated in cells far (>0.3 cm) from wounds, which is mediated by diffusion of extracellular ATP because activation at a distance from wounds is abrogated by eliminating ATP in the medium with apyrase. In sharp contrast, activation of the EGFR near wounds is not sensitive to apyrase. Time-lapse microscopy revealed that cells exhibit increased motilities near edges of wounds; this increase in motility is not sensitive to apyrase, and apyrase does not detectably inhibit healing of wounds in epithelial sheets. This novel ATP/PLD2-independent pathway activates the EGFR by a transactivation process through ligand release, and it involves signaling by a member of the Src family of kinases. We conclude that wounding activates two distinct signaling pathways that induce EGFR activation and promote healing of wounds in epithelial cells. One pathway signals at a distance from wounds through release of ATP, and another pathway acts locally and is independent on ATP signaling.
An FTS/Hook/p107FHIPComplex Interacts with and Promotes Endosomal Clustering by the Homotypic Vacuolar Protein Sorting Complex
Authors: Xu Lai , Sowa Mathew E. , Chen Jing , Li Xue , Gygi Steven P. , Harper J. Wade
Published: September 2008

Fused Toes (FTS) is a member of a small group of inactive variant E2 ubiquitin-conjugating enzyme domain-containing proteins of unknown function. Through proteomic analysis of FTS complexes purified from human embryonic kidney 293T cells, we identified a new multiprotein complex, the FHF complex, containing FTS, members of the microtubule-binding Hook family of coiled-coil proteins (Hook1, Hook2, and Hook3), and a previously uncharacterized 107-kDa protein, FTS and Hook Interacting Protein (FHIP). FTS associated with a conserved C-terminal motif in Hook proteins in the yeast two-hybrid system and in tissue culture cells, and Hook proteins were found to form homo- and heterodimers. The ∼500-kDa FHF complex contained all three Hook proteins, and small interfering RNA depletion experiments suggest that Hook proteins can interact interchangeably within this complex. Hook proteins as well as FTS interact with members of both the class B and class C components of the homotypic vesicular protein sorting (HOPS) complex. Depletion of FTS by RNA interference affects both the trafficking of epidermal growth factor from early-to-late endosome/lysosomes and the efficiency by which overexpression of the HOPS component Vps18 promotes clustering of lysosomal-associated membrane protein 1-positive endosome/lysosomes. These data suggest that the FTS/Hook/FHIP complex functions to promote vesicle trafficking and/or fusion via the HOPS complex.
Snail and Slug Promote Epithelial-Mesenchymal Transition through β-Catenin–T-Cell Factor-4-dependent Expression of Transforming Growth Factor-β3
Authors: Medici Damian , Hay Elizabeth D. , Olsen Bjorn R.
Published: September 2008

Members of the Snail family of transcription factors have been shown to induce epithelial-mesenchymal transition (EMT), a fundamental mechanism of embryogenesis and progressive disease. Here, we show that Snail and Slug promote formation of β-catenin–T-cell factor (TCF)-4 transcription complexes that bind to the promoter of the TGF-β3 gene to increase its transcription. Subsequent transforming growth factor (TGF)-β3 signaling increases LEF-1 gene expression causing formation of β-catenin–lymphoid enhancer factor (LEF)-1 complexes that initiate EMT. TGF-β1 or TGF-β2 stimulates this signaling mechanism by up-regulating synthesis of Snail and Slug. TGF-β1- and TGF-β2-induced EMT were found to be TGF-β3 dependent, establishing essential roles for multiple TGF-β isoforms. Finally, we determined that β-catenin–LEF-1 complexes can promote EMT without upstream signaling pathways. These findings provide evidence for a unified signaling mechanism driven by convergence of multiple TGF-β and TCF signaling molecules that confers loss of cell–cell adhesion and acquisition of the mesenchymal phenotype.
HST3/HST4-dependent Deacetylation of Lysine 56 of Histone H3 in Silent Chromatin
Authors: Yang Bo , Miller Andrew , Kirchmaier Ann L.
Published: September 2008

The composition of posttranslational modifications on newly synthesized histones must be altered upon their incorporation into chromatin. These changes are necessary to maintain the same gene expression state at individual chromosomal loci before and after DNA replication. We have examined how one modification that occurs on newly synthesized histone H3, acetylation of K56, influences gene expression at epigenetically regulated loci in Saccharomyces cerevisiae. H3 K56 is acetylated by Rtt109p before its incorporation into chromatin during S phase, and this modification is then removed by the NAD+-dependent deacetylases Hst3p and Hst4p during G2/M phase. We found silenced loci maintain H3 K56 in a hypoacetylated state, and the absence of this modification in rtt109 mutants was compatible with HM and telomeric silencing. In contrast, loss of HST3 and HST4 resulted in hyperacetylation of H3 K56 within silent loci and telomeric silencing defects, despite the continued presence of Sir2p throughout these loci. These silencing defects in hst3Δ hst4Δ mutants could be suppressed by deletion of RTT109. In contrast, overexpression of Sir2p could not restore silencing in hst3Δ hst4Δ mutants. Together, our findings argue that HST3 HST4 play critical roles in maintaining the hypoacetylated state of K56 on histone H3 within silent chromatin.
eEF1A Is a Novel Component of the Mammalian Nuclear Protein Export Machinery
Authors: Khacho Mireille , Mekhail Karim , Pilon-Larose Karine , Pause Arnim , Côté Jocelyn , Lee Stephen
Published: September 2008

The cytoplasmic translation factor eEF1A has been implicated in the nuclear export of tRNA species in lower eukaryotes. Here we demonstrate that eEF1A plays a central role in nuclear export of proteins in mammalian cells. TD-NEM (transcription-dependent nuclear export motif), a newly characterized nuclear export signal, mediates efficient nuclear export of several proteins including the von Hippel-Lindau (VHL) tumor suppressor and the poly(A)-binding protein (PABP1) in a manner that is dependent on ongoing RNA polymerase II (RNA PolII)-dependent transcription. eEF1A interacts specifically with TD-NEM of VHL and PABP1 and disrupting this interaction, by point mutations of key TD-NEM residues or treatment with actinomycin D, an inhibitor of RNA PolII-dependent transcription, prevents assembly and nuclear export. siRNA-induced knockdown or antibody-mediated depletion of eEF1A prevents in vivo and in vitro nuclear export of TD-NEM–containing proteins. Nuclear retention experiments and inhibition of the Exportin-5 pathway suggest that eEF1A stimulates nuclear export of proteins from the cytoplasmic side of the nuclear envelope, without entering the nucleus. Together, these data identify a role for eEF1A, a cytoplasmic mediator of tRNA export in yeast, in the nuclear export of proteins in mammalian cells. These results also provide a link between the translational apparatus and subcellular trafficking machinery demonstrating that these two central pathways in basic metabolism can act cooperatively.
Hepatoma Up-Regulated Protein Is Required for Chromatin-induced Microtubule Assembly Independently of TPX2
Authors: Casanova Claudia M. , Rybina Sofia , Yokoyama Hideki , Karsenti Eric , Mattaj Iain W.
Published: September 2008

The production of RanGTP around chromosomes is crucial for spindle microtubule assembly in mitosis. Previous work has shown that hepatoma up-regulated protein (HURP) is a Ran target, required for microtubule stabilization and spindle organization. Here we report a detailed analysis of HURP function in Xenopus laevis mitotic egg extracts. HURP depletion severely impairs bipolar spindle assembly around chromosomes: the few spindles that do form show a significant decrease in microtubule density at the spindle midzone. HURP depletion does not interfere with microtubule growth from purified centrosomes, but completely abolishes microtubule assembly induced by chromatin beads or RanGTP. Simultaneous depletion of the microtubule destabilizer MCAK with HURP does not rescue the phenotype, demonstrating that the effect of HURP is not to antagonize the destabilization activity of MCAK. Although the phenotype of HURP depletion closely resembles that reported for TPX2 depletion, we find no evidence that TPX2 and HURP physically interact or that they influence each other in their effects on spindle microtubules. Our data indicate that HURP and TPX2 have nonredundant functions essential for chromatin-induced microtubule assembly.
Effect of Proliferating Cell Nuclear Antigen Ubiquitination and Chromatin Structure on the Dynamic Properties of the Y-family DNA Polymerases
Authors: Sabbioneda Simone , Gourdin Audrey M. , Green Catherine M. , Zotter Angelika , Giglia-Mari Giuseppina , Houtsmuller Adriaan , Vermeulen Wim , Lehmann Alan R.
Published: September 2008

Y-family DNA polymerases carry out translesion synthesis past damaged DNA. DNA polymerases (pol) η and ι are usually uniformly distributed through the nucleus but accumulate in replication foci during S phase. DNA-damaging treatments result in an increase in S phase cells containing polymerase foci. Using photobleaching techniques, we show that polη is highly mobile in human fibroblasts. Even when localized in replication foci, it is only transiently immobilized. Although ubiquitination of proliferating cell nuclear antigen (PCNA) is not required for the localization of polη in foci, it results in an increased residence time in foci. polι is even more mobile than polη, both when uniformly distributed and when localized in foci. Kinetic modeling suggests that both polη and polι diffuse through the cell but that they are transiently immobilized for ∼150 ms, with a larger proportion of polη than polι immobilized at any time. Treatment of cells with DRAQ5, which results in temporary opening of the chromatin structure, causes a dramatic immobilization of polη but not polι. Our data are consistent with a model in which the polymerases are transiently probing the DNA/chromatin. When DNA is exposed at replication forks, the polymerase residence times increase, and this is further facilitated by the ubiquitination of PCNA.
GenMiner: mining non-redundant association rules from integrated gene expression data and annotations
Authors: Martinez Ricardo , Pasquier Nicolas , Pasquier Claude
Published: September 2008

Summary: GenMiner is an implementation of association rule discovery dedicated to the analysis of genomic data. It allows the analysis of datasets integrating multiple sources of biological data represented as both discrete values, such as gene annotations, and continuous values, such as gene expression measures. GenMiner implements the new NorDi (normal discretization) algorithm for normalizing and discretizing continuous values and takes advantage of the Close algorithm to efficiently generate minimal non-redundant association rules. Experiments show that execution time and memory usage of GenMiner are significantly smaller than those of the standard Apriori-based approach, as well as the number of extracted association rules.

Availability: The GenMiner software and supplementary materials are available at http://bioinfo.unice.fr/publications/genminer_article/ and http://keia.i3s.unice.fr/?Implementations:GenMiner

Contact:  pasquier@unice.fr

Supplementary information:  Supplementary data are available at Bioinformatics online.
The Telephone Patents: Intellectual Property, Business, and the Law in the United States and Britain, 1876—1900
Authors: Beauchamp Christopher
Published: September 2008

This dissertation summary introduces a new perspective on the legal and economic history of patents in the late nineteenth century. Through a case study of the early telephone industry in Britain and the United States, the dissertation explores interactions between business strategies and national legal regimes, and proposes a revised view of the multi-layered relationship between patents and industrial organization.
Influence of anatomical hooking depth, capture depth, and venting on mortality of painted comber (Serranus scriba) released by recreational anglers
Authors: Alós Josep
Published: September 2008

Alós, J. 2008. Influence of anatomical hooking depth, capture depth, and venting on mortality of painted comber (Serranus scriba) released by recreational anglers. – ICES Journal of Marine Science, 65: 1620–1625. Immediate (4–5 h) and delayed (10 d) hooking mortality for released fish kept in tanks was evaluated for painted comber (Serranus scriba) taken by the recreational fishery of the Balearic Islands (western Mediterranean). Results showed low rates of immediate (10.8%) and delayed (3.3%) hooking mortality, a total mortality of 14.1%. Anatomical hook location and capture depth were the most significant predictors of mortality; 70.4% of fish caught with a deep location of hook died as a consequence of the damage caused, bleeding, and long unhooking times. Fish caught in depths >16 m showed evidence of external barotrauma caused by rapid decompression, which increased the probability of death. The most common forms of barotrauma were swimbladder enlargement and stomach inversion. For fish vented with the aid of a hypodermic needle to extract excess gas, mortality was reduced by half. Factors such as surface temperature, fish size, and hook type (“J” hook vs. circle hook) could not explain the mortality of fish released into tanks. Therefore, the results confirm that a practice of catch-and-release (voluntary or mandatory) for S. scriba needs to be promoted among recreational anglers.
Beyond existence and aiming outside the laboratory: estimating frequency-dependent and pay-off-biased social learning strategies
Authors: McElreath Richard , Bell Adrian V , Efferson Charles , Lubell Mark , Richerson Peter J , Waring Timothy
Published: September 2008

The existence of social learning has been confirmed in diverse taxa, from apes to guppies. In order to advance our understanding of the consequences of social transmission and evolution of behaviour, however, we require statistical tools that can distinguish among diverse social learning strategies. In this paper, we advance two main ideas. First, social learning is diverse, in the sense that individuals can take advantage of different kinds of information and combine them in different ways. Examining learning strategies for different information conditions illuminates the more detailed design of social learning. We construct and analyse an evolutionary model of diverse social learning heuristics, in order to generate predictions and illustrate the impact of design differences on an organism's fitness. Second, in order to eventually escape the laboratory and apply social learning models to natural behaviour, we require statistical methods that do not depend upon tight experimental control. Therefore, we examine strategic social learning in an experimental setting in which the social information itself is endogenous to the experimental group, as it is in natural settings. We develop statistical models for distinguishing among different strategic uses of social information. The experimental data strongly suggest that most participants employ a hierarchical strategy that uses both average observed pay-offs of options as well as frequency information, the same model predicted by our evolutionary analysis to dominate a wide range of conditions.
Exploring gene–culture interactions: insights from handedness, sexual selection and niche-construction case studies
Authors: Laland Kevin N
Published: September 2008

Genes and culture represent two streams of inheritance that for millions of years have flowed down the generations and interacted. Genetic propensities, expressed throughout development, influence what cultural organisms learn. Culturally transmitted information, expressed in behaviour and artefacts, spreads through populations, modifying selection acting back on populations. Drawing on three case studies, I will illustrate how this gene–culture coevolution has played a critical role in human evolution. These studies explore (i) the evolution of handedness, (ii) sexual selection with a culturally transmitted mating preference, and (iii) cultural niche construction and human evolution. These analyses shed light on how genes and culture shape each other, and on the significance of feedback mechanisms between biological and cultural processes.
Investigating children as cultural magnets: do young children transmit redundant information along diffusion chains?
Authors: Flynn Emma
Published: September 2008

The primary goal of this study was to investigate cultural transmission in young children, with specific reference to the phenomenon of overimitation. Diffusion chains were used to compare the imitation of 2- and 3-year-olds on a task in which the initial child in each chain performed a series of relevant and irrelevant actions on a puzzle box in order to retrieve a reward. Children in the chains witnessed the actions performed on one of two boxes, one which was transparent and so the lack of causality of the irrelevant actions was obvious, while the other was opaque and so the lack of causal relevance was not obvious. Unlike previous dyadic research in which children overimitate a model, the irrelevant actions were parsed out early in the diffusion chains. Even though children parsed out irrelevant actions, they showed fidelity to the method used to perform a relevant action both within dyads and across groups. This was true of 3-year-olds, and also 2-year-olds, therefore extending findings from previous research.
The Pollen Receptor Kinase LePRK2 Mediates Growth-Promoting Signals and Positively Regulates Pollen Germination and Tube Growth
Authors: Zhang Dong , Wengier Diego , Shuai Bin , Gui Cai-Ping , Muschietti Jorge , McCormick Sheila , Tang Wei-Hua
Published: September 2008

In flowering plants, the process of pollen germination and tube growth is required for successful fertilization. A pollen receptor kinase from tomato (Solanum lycopersicum), LePRK2, has been implicated in signaling during pollen germination and tube growth as well as in mediating pollen (tube)-pistil communication. Here we show that reduced expression of LePRK2 affects four aspects of pollen germination and tube growth. First, the percentage of pollen that germinates is reduced, and the time window for competence to germinate is also shorter. Second, the pollen tube growth rate is reduced both in vitro and in the pistil. Third, tip-localized superoxide production by pollen tubes cannot be increased by exogenous calcium ions. Fourth, pollen tubes have defects in responses to style extract component (STIL), an extracellular growth-promoting signal from the pistil. Pollen tubes transiently overexpressing LePRK2-fluorescent protein fusions had slightly wider tips, whereas pollen tubes coexpressing LePRK2 and its cytoplasmic partner protein KPP (a Rop-GEF) had much wider tips. Together these results show that LePRK2 positively regulates pollen germination and tube growth and is involved in transducing responses to extracellular growth-promoting signals.
Diversification of Photoperiodic Response Patterns in a Collection of Early-Flowering Mutants of Arabidopsis
Authors: Pouteau Sylvie , Carré Isabelle , Gaudin Valérie , Ferret Valérie , Lefebvre Delphine , Wilson Melanie
Published: September 2008

Many plant species exhibit seasonal variation of flowering time in response to daylength. Arabidopsis (Arabidopsis thaliana) flowers earlier under long days (LDs) than under short days (SDs). This quantitative response to photoperiod is characterized by two parameters, the critical photoperiod (Pc), below which there is a delay in flowering, and the ceiling photoperiod (Pce), below which there is no further delay. Thus Pc and Pce define the thresholds beyond which maximum LD and SD responses are observed, respectively. We studied the quantitative response to photoperiod in 49 mutants selected for early flowering in SDs. Nine of these mutants exhibited normal Pce and Pc, showing that their precocious phenotype was not linked to abnormal measurement of daylength. However, we observed broad diversification in the patterns of quantitative responses in the other mutants. To identify factors involved in abnormal measurement of daylength, we analyzed the association of these various patterns with morphogenetic and rhythmic defects. A high proportion of mutants with altered Pce exhibited abnormal hypocotyl elongation in the dark and altered circadian periods of leaf movements. This suggested that the circadian clock and negative regulators of photomorphogenesis may contribute to the specification of SD responses. In contrast, altered Pc correlated with abnormal hypocotyl elongation in the light and reduced photosynthetic light-input requirements for bolting. This indicated that LD responses may be specified by positive elements of light signal transduction pathways and by regulators of resource allocation. Furthermore, the frequency of circadian defects in mutants with normal photoperiodic responses suggested that the circadian clock may regulate the number of leaves independently of its effect on daylength perception.
Functional Characterization of the Plastidic Phosphate Translocator Gene Family from the Thermo-Acidophilic Red Alga Galdieria sulphuraria Reveals Specific Adaptations of Primary Carbon Partitioning in Green Plants and Red Algae
Authors: Linka Marc , Jamai Aziz , Weber Andreas P.M.
Published: September 2008

In chloroplasts of green plants and algae, CO2 is assimilated into triose-phosphates (TPs); a large part of these TPs is exported to the cytosol by a TP/phosphate translocator (TPT), whereas some is stored in the plastid as starch. Plastidial phosphate translocators have evolved from transport proteins of the host endomembrane system shortly after the origin of chloroplasts by endosymbiosis. The red microalga Galdieria sulphuraria shares three conserved putative orthologous transport proteins with the distantly related seed plants and green algae. However, red algae, in contrast to green plants, store starch in their cytosol, not inside plastids. Hence, due to the lack of a plastidic starch pool, a larger share of recently assimilated CO2 needs to be exported to the cytosol. We thus hypothesized that red algal transporters have distinct substrate specificity in comparison to their green orthologs. This hypothesis was tested by expression of the red algal genes in yeast (Saccharomyces cerevisiae) and assessment of their substrate specificities and kinetic constants. Indeed, two of the three red algal phosphate translocator candidate orthologs have clearly distinct substrate specificities when compared to their green homologs. GsTPT (for G. sulphuraria TPT) displays very narrow substrate specificity and high affinity; in contrast to green plant TPTs, 3-phosphoglyceric acid is poorly transported and thus not able to serve as a TP/3-phosphoglyceric acid redox shuttle in vivo. Apparently, the specific features of red algal primary carbon metabolism promoted the evolution of a highly efficient export system with high affinities for its substrates. The low-affinity TPT of plants maintains TP levels sufficient for starch biosynthesis inside of chloroplasts, whereas the red algal TPT is optimized for efficient export of TP from the chloroplast.
N
6-Substituted 2-amino-4-chloro-5-formylpyrimidines: puckered versus planar pyrimidine rings, and hydrogen-bonded aggregation in zero, one, two and three dimensions
Authors: Cobo Justo , Trilleras Jorge , Quiroga Jairo , Marchal Antonio , Nogueras Manuel , Low John N. , Glidewell Christopher
Published: September 2008

The structures of 12 new N
6-substituted 2-amino-4-chloro-5-formylpyrimidines, where the N
6 substituent is of the type NHR or NR
1
R
2, have been determined. The intramolecular dimensions provide strong evidence for the development of polarized, charge-separated molecular-electronic structures, with the positive charge delocalized over the two exocyclic amino N atoms and with negative charge on the formyl O atom. This polarization appears to be independent of the significant puckering, in seven of the compounds, of the pyrimidine rings from planarity towards boat, twist-boat or screw-boat conformations. In 11 of the compounds studied here, N—H...N hydrogen bonds link pairs of molecules into centrosymmetric R_2^2(8) dimer units, and their overall crystal structures are determined by the patterns of hydrogen bonds by which these units are further linked. Examples are reported in which no further hydrogen bonding occurs; in which the R_2^2(8) dimers are linked into chains of rings, or into sheets; and in which sheets are formed by the π-stacking of hydrogen-bonded chains of rings. In the sole structure lacking the R_2^2(8) dimer motif, N—H...O and N—H...N hydrogen bonds cooperate to generate a three-dimensional framework structure.
A room-temperature X-ray diffuse scattering study of form (II) of the trimorphic molecular system p-(N-methylbenzylidene)-p-methylaniline
Authors: Beasley A. G. , Welberry T. R. , Goossens D. J. , Heerdegen A. P.
Published: September 2008

Three-dimensional X-ray diffuse scattering data have been collected at room temperature for form (II) of the trimorphic molecular system p-(N-methylbenzylidene)-p-methylaniline. Although this polymorph has been reported to have a perfectly normal ordered average structure, strong and highly structured diffuse scattering was observed, indicating that substantial thermal disorder is present. A diffuse scattering analysis has been carried out using Monte Carlo simulation techniques. Narrow streaks of intensity extending between Bragg peaks in the h0l section were found to arise from planes of diffuse scattering in three dimensions. These are caused by highly correlated molecular displacements along chains of end-to-end disposed molecules running in the a\!-\!c direction, corresponding to methyl–methyl intermolecular interactions. A second significant feature – rods of diffuse scattering running in the b^* direction – indicates that molecular layers normal to b have a tendency to undergo lateral displacements with little correlation between layers. Finally, the internal flexibility of the molecule is required for a best fit. Changes in the two dihedral angles are found to be strongly correlated and show large excursions (\gt\pm20^{\circ}) from the average values. All of these features suggest possible mechanisms for the way in which form (II) might transform to other polymorphs.
Increased plasma ghrelin following infliximab in Crohn’s disease
Authors: SUNG E. Z. H. , DA SILVA N. F. , GOODYEAR S. , MCTERNAN P. G. , SANGER G. J. , NWOKOLO C. U.
Published: September 2008

Background  Ghrelin, a potent orexigenic peptide produced by the stomach, may be affected by circulating inflammatory mediators.

Aim  To assess the effect of an anti‐TNFα antibody on ghrelin in patients with Crohn’s disease (CD).

Methods  Fifteen patients with Crohn’s receiving infliximab were studied before and 1 week after infusion. Following an overnight fast, blood was sampled before a meal and then every 20 min for 2 h. Total ghrelin and CRP were measured using ELISA. Acylated ghrelin and TNFα, IFNγ, IL‐1β and IL‐6 were measured with bioplex. Harvey Bradshaw Activity Index was assessed.

Results  Median (95% CI) 2‐h integrated plasma total ghrelin increased from 162 (99–311) before infliximab to 200 (128–387) pg/mL h, (P = 0.02) after. Following infliximab, 20 min postmeal, median acylated ghrelin decreased from 50.3 (24–64) to 38.6 (26–82) pg/mL, (P = 0.04) thus reverting to a traditional meal related ghrelin curve. Median (range) disease activity decreased from 5 (2–28) before to 3 (0–22), (P = 0.0001) and Median (95% CI) TNFα decreased from 2.8 (1.89–4.48) to 1.31 (0.73–2.06) pg/mL (P = 0.002).

Conclusions  Infliximab increases circulating total ghrelin by 25% in CD and restores the postprandial response of acylated ghrelin to food intake. Acylated and de‐sacyl ghrelin remain unchanged, suggesting that an alternate isoform could be affected by infliximab.
Augmentation index in resistance to thyroid hormone (RTH)
Authors: Owen P. J. D. , Chatterjee V. K. , John R. , Halsall D. , Lazarus J. H.
Published: September 2008

Objective  Resistance to thyroid hormone (RTH) is associated with a varied clinical presentation. The cardiac effects of RTH have been described but vascular function has yet to be fully evaluated in this condition. We have measured the arterial function of those with RTH to assess any vascular changes.

Design  An observational study.

Patients  Twelve RTH patients were recruited from the thyroid clinic (mean value ± SD), age 40·8 ± 18·7 years; BMI 27·2 ± 4·2 kg/m2 and compared with 12 healthy, euthyroid, age‐matched controls (age 41·4 ± 19·3; BMI 24·8 ± 4·4 kg/m2) with no history of cardiovascular disease. No interventional measures were instituted.

Measurements  Arterial stiffness was measured using pulse wave analysis at the radial artery. Thyroid function, fasting lipids and glucose were also measured on the same occasion in both patients and controls.

Results  The corrected augmentation index, a surrogate marker of arterial stiffness was significantly higher in patients compared with controls (21·0% ± 14·1%vs. 5·4% ± 18·2%, P < 0·03). Low density lipoprotein cholesterol (LDL‐cholesterol) levels were also significantly elevated in patients compared with controls (3·0 ± 0·6 vs. 2·1 ± 0·5 mmol/l; P < 0·002).

Conclusion  RTH patients show evidence in this study of increased augmentation index consistent with an increase in arterial stiffness compared with euthyroid controls. They also demonstrate elevated LDL‐cholesterol levels. Both these measures may lead to increased cardiovascular risk.
Leptin concentration indexed to fat mass is increased in untreated anorexia nervosa (AN) patients
Authors: Uzum Ayse Kubat , Yucel Basak , Omer Beyhan , Issever Halim , Ozbey Nese Colak
Published: September 2008

Context  Data regarding serum adipocytokine and ghrelin concentrations in different stages of anorexia nervosa (AN) is conflicting.

Objective  Our aim is to determine serum concentrations of adiponectin (ApN), leptin and ghrelin in different stages of AN and to evaluate their relationships with study parameters.

Design setting and participants  Study group was composed of four subgroups: Group 1: patients with a recent diagnosis of AN (n = 19); group 2: weight recovered (10% increase in body weight compared with baseline) subgroup of group 1 during follow‐up (n = 10); group 3: recovered patients with a previous history of AN but normal menstrual cycles and body weight currently (n = 10); group 4: control group (n = 10). Venous blood was obtained for measurements of biochemical/hormonal parameters, ApN, leptin and ghrelin. Body composition was determined by bioimpedance analysis.

Main outcome measures  Changes in adipocytokine and ghrelin concentrations and relationships with anthropometric/biochemical parameters.

Results  Leptin : fat mass (kg) ratio was significantly higher in group 1 patients compared with group 4 (4·3 ± 4·6 vs. 1·1 ± 0·5 µg/l kg, P < 0·01). No significant difference was observed among ghrelin concentrations. Leptin showed significant positive correlation with body fat mass in all groups. ApN showed significant positive association with body mass index in Group 1.

Conclusions  Leptin concentrations indexed to fat mass may indicate a nonphysiological higher set point of leptin per unit fat mass in treatment‐naive AN patients. Correlation pattern between ApN and fat mass is modified also. Altered adipocytokine profile in AN may contribute to anorectic behaviour.
Nurses’ experience in clinical encounters with children experiencing abuse and their parents
Authors: Tingberg Björn , Bredlöv Britt , Ygge Britt‐Marie
Published: September 2008

Aim and objectives.  The aim of this study was to identify nurse’s experiences in the clinical care of children experiencing abuse. The objective was to assess how nurses remain professional especially when the suspected perpetrator is a parent.

Background.  The diagnosis of child abuse is a difficult one, yet essential because of the high morbidity and significant mortality rates. Young children may be unable to give a clear history; parents may be unwilling to be truthful, and the signs and symptoms of abuse are often not conclusive. A contributing factor to the challenges of providing nursing care to children in a context of abuse is the lack of education in this field. Nurses working in the care of paediatric patients may not be familiar with situations in which they cannot rely on histories provided by parents.

Design.  A qualitative study.

Methods.  Investigators used a qualitative design with a critical incident technique. Eleven nurses who cared for abused children and their parents at a tertiary care children’s hospital were interviewed.

Results.  We highlighted three areas in the analysis of the interviews: Feelings of ambivalence, nurses’ professionalism and the nurses’ care strategies. Participants expressed difficulties in maintaining a professional role in clinical encounters with the parents. The nurses were unhappy in their conflicting roles of both policing (a judging function) and nursing (a caring function).

Conclusions.  The nurses expressed that they had devised strategies to remain professional in the clinical encounter with abused children and their parents. To remain professional, education, counselling and experience was essential.

Relevance to clinical practice.  By identifying nurses’ experiences in clinical encounters with children experiencing abuse and their parents, nurses can assess what kind of specific interventions should be used to improve the caring situation.
Patients’ expectations of the maintenance of their dignity
Authors: Matiti Milika R , Trorey Gillian M
Published: September 2008

Aims and objectives.  To explore patients’ views regarding the factors that contribute to the maintenance of their dignity while in hospital, together with their perceptions of whether or not these were realised.

Background.  It has long been recognised that a consideration of patients’ dignity in the hospital setting is of paramount importance and its maintenance can contribute to the ‘emotional comfort’ that may assist recovery. There have been several attempts to define dignity as a theoretical concept, but few studies of the factors that contribute to its maintenance from the patients’ perspective.

Design.  A phenomenological hermeneutic approach was used.

Method.  Interviews were conducted with 102 patients in three hospitals in the UK over 18 months. The intention was to interpret what was being said and also the underlying meaning of how patients considered that their dignity was compromised.

Results.  The findings revealed that although many patients were satisfied with the maintenance of their dignity while in hospital, a significant number were not. Six key themes that contribute to the preservation of their dignity were identified – privacy; confidentiality; communication and the need for information; choice, control and involvement in care; respect and decency and forms of address. Patients provided details of their expectations with respect to these factors.

Conclusions.  Patients, irrespective of their situation and degree of health have their own expectations in relation to their dignity. These need to be assessed and matched by relevant nursing activities to assist recovery.

Relevance to clinical practice.  Nurses have an important role in meeting patients’ expectations of how they would like their dignity to be maintained. The identification of the most important factors that contribute to this from patients’ perspective will help develop dignified nursing practice.
The effectiveness of an educational programme for nursing students on developing competence in the provision of spiritual care
Authors: Van Leeuwen René , Tiesinga Lucas J , Middel Berrie , Post Doeke , Jochemsen Henk
Published: September 2008

Aim.  To determine the effects of a course for nursing students on developing competence in spiritual care and the factors that might influence the effects.

Background.  Studies suggest that role preparation in nursing for spiritual care is poor. For the assessment of competence, few or no explicit competency framework or assessment tools seemed to be used.

Design.  Quasi‐experimental crossover design (pre–post‐test).

Method.  The subjects were students from Christian nursing schools in the Netherlands (n = 97). The intervention consisted of a course in spiritual care. Competencies were measured with an assessment tool, the Spiritual Care Competence Scale. Data were analysed by t‐test procedures (paired‐samples t‐test). At T1 vignettes were added to assess the quality of the students’ own analyses. These data were analysed by a Mann–Whitney test. Regression analyses were performed on the influence of student characteristics on the subscales of the assessment tool.

Results.  Ninety‐seven students participated in this study. Analysis showed statistically significant changes in scores on three subscales of the Spiritual Care Competence Scale between groups (T1) and over time for the whole cohort of students on all subscales (T2). Clinical placement showed as a negative predictor for three subscales of the Spiritual Care Competence Scale. Experience in spiritual care and a holistic vision of nursing both showed as positive predictors on certain competencies. A statistically significant difference was observed between groups in the student analysis of a vignette with explicit spiritual content.

Conclusions.  The outcomes raise questions about the content of education in spiritual care, the measurement of competencies and the factors that influence competency development.

Relevance to clinical practice.  The results provide nurse educators with insight into the effects of education in spiritual care on students’ competencies and help them consider a systematic place for spiritual care within the nursing curriculum.
Use of drug therapy in children with attention deficit hyperactivity disorder (ADHD): maternal views and experiences
Authors: Jackson Debra , Peters Kathleen
Published: September 2008

Aims and objectives.  The aim of this paper is to explore maternal views and experiences of stimulant pharmacotherapy in children with attention deficit hyperactivity disorder (ADHD).

Background.  The very nature of ADHD means that it exists in a climate of scepticism and doubt. However, parents must make decisions about how to treat their children affected by ADHD. Of the treatments available, the use of stimulant therapy is the most controversial.

Design.  Qualitative.

Method.  Snowball sampling was used to recruit mothers (n = 11) of children with ADHD and a narrative‐based qualitative methodology was used.

Results.  Decisions around the use of stimulant medication for children with ADHD were difficult for these mothers. Detailed findings are presented under the themes of: Ambivalence and confusion: everybody would be down on me like a ton of bricks; Influence of the media: so much bad publicity; Deciding against medication: you’re changing their whole personality; and, Deciding for medication: he’s just been wonderful.

Conclusions.  While these mothers revealed that they were discriminating in selecting information to guide their decision‐making, many of their friends and family were influenced solely by media reports. Mothers experienced misgivings from family and friends who were sceptical about the need for medication and the implications and ethics of administering stimulant medication to children.

Relevance to clinical practice.  Nurses and healthcare professionals have an important role in providing accurate and current information for parents and families and should be aware of the pressures parents are under when making decisions about treatments for their children with ADHD.
Parental experience of family resources in single‐parent families having a child with cancer
Authors: Huang I‐Chen , Mu Pei‐Fan , Chiou Tzeon‐Jye
Published: September 2008

Aim.  The purpose of this study was to explore the essence of family experiences in terms of family resources and how these assist a single‐parent caring for a child with cancer.

Background.  When families face stresses caused by cancer, they need to readjust their roles, interactive patterns and relationships, both inside and outside the family. During the adaptation process, family resources may assist recovery from stress and a return to equilibrium. Most research has emphasised the support resources available to two‐parent families during the treatment process. There is a lack of information on the experiences of single‐parent families and their available resources together with the functions and roles played by family resources during the adjustment process.

Design.  Qualitative.

Results.  Five major themes were identified: (i) facing the disease with courage; (ii) hope kindled by professionals; (iii) constructing parental role ability; (iv) assisting the children to live with the illness; and (v) family flexibility.

Conclusion.  The results of the current study demonstrate that single‐parent families with a child suffering from cancer employ family resources to assist family adjustment and to maintain family function/equilibrium. These results explain the dynamic interactions between the multiple levels of resources available to the family.

Relevance to clinical practice.  The study results provide evidence‐based information that identifies the nature of family resources in single‐parent families and describes how these resources can be applied to assist the families.
Coping mechanisms of parents of children recently diagnosed with autism in Taiwan: a qualitative study
Authors: Lin Ching‐Rong , Tsai Yun‐Fang , Chang Hsueh‐Ling
Published: September 2008

Objective.  To understand the coping mechanisms of Taiwanese parents whose children have recently been diagnosed with autism.

Background.  When a child is diagnosed with autism, the family’s life changes. Parents of a child with autism have been shown to cope with problem‐ or emotion‐focused coping strategies. However, it is not known how parents in Taiwan adapt and cope with the stresses of taking care of an autistic child, especially in the early period after learning their child’s diagnosis and while waiting for free national day care arrangements at hospital.

Design.  A descriptive qualitative design was used, with in‐depth interviews.

Methods.  Parents of children diagnosed with autism (n = 17) were recruited from a children’s psychiatric outpatient clinic at a medical centre in northern Taiwan. The parents were still waiting for free national day care arrangements at hospital. Data were collected through individual, tape‐recorded interviews and observations, and transcripts were analysed by content analysis for emerging themes and concepts.

Results.  The study sample of parents of children with autism described nine main coping mechanisms that fell into three core categories: adjusting to self‐change, developing treatments for the autistic child and seeking support.

Conclusions.  The results of this study could be used by clinicians to help parents of autistic children become aware of whether or not they are using healthy coping mechanisms, and to suggest concrete and healthy coping strategies, particularly in the period after the diagnosis is confirmed and they are waiting for free national day care arrangements at hospital.

Relevance to clinical practice.  Clinicians in child psychiatry are encouraged to become part of the social support network for parents of autistic children, thus helping them adjust to the long journey of caring for their children.