bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinetic and structural analysis of a bacterial protein tyrosine phosphatase‐like myo‐inositol polyphosphatase
Authors: Puhl Aaron A. , Gruninger Robert J. , Greiner Ralf , Janzen Timothy W. , Mosimann Steven C. , Selinger L. Brent
Published: June 2007

PhyA from Selenomonas ruminantium (PhyAsr), is a bacterial protein tyrosine phosphatase (PTP)‐like inositol polyphosphate phosphatase (IPPase) that is distantly related to known PTPs. PhyAsr has a second substrate binding site referred to as a standby site and the P‐loop (HCX5R) has been observed in both open (inactive) and closed (active) conformations. Site‐directed mutagenesis and kinetic and structural studies indicate PhyAsr follows a classical PTP mechanism of hydrolysis and has a broad specificity toward polyphosphorylated myo‐inositol substrates, including phosphoinositides. Kinetic and molecular docking experiments demonstrate PhyAsr preferentially cleaves the 3‐phosphate position of Ins P6 and will produce Ins(2)P via a highly ordered series of sequential dephosphorylations: D‐Ins(1,2,4,5,6)P5, Ins(2,4,5,6)P4, D‐Ins(2,4,5)P3, and D‐Ins(2,4)P2. The data support a distributive enzyme mechanism and suggest the PhyAsr standby site is involved in the recruitment of substrate. Structural studies at physiological pH and high salt concentrations demonstrate the “closed” or active P‐loop conformation can be induced in the absence of substrate. These results suggest PhyAsr should be reclassified as a D‐3 myo‐inositol hexakisphosphate phosphohydrolase and suggest the PhyAsr reaction mechanism is more similar to that of PTPs than previously suspected.
A high‐throughput method for membrane protein solubility screening: The ultracentrifugation dispersity sedimentation assay
Authors: Gutmann Daniel A.P. , Mizohata Eiichi , Newstead Simon , Ferrandon Sebastian , Henderson Peter J.F. , van Veen Hendrik W. , Byrne Bernadette
Published: June 2007

One key to successful crystallization of membrane proteins is the identification of detergents that maintain the protein in a soluble, monodispersed state. Because of their hydrophobic nature, membrane proteins are particularly prone to forming insoluble aggregates over time. This nonspecific aggregation of the molecules reduces the likelihood of the regular association of the protein molecules essential for crystal lattice formation. Critical buffer components affecting the aggregation of membrane proteins include detergent choice, salt concentration, and presence of glycerol. The optimization of these parameters is often a time‐ and protein‐consuming process. Here we describe a novel ultracentrifugation dispersity sedimentation (UDS) assay in which ultracentrifugation of very small (5 μL) volumes of purified, soluble membrane protein is combined with SDS‐PAGE analysis to rapidly assess the degree of protein aggregation. The results from the UDS method correlate very well with established methods like size‐exclusion chromatography (SEC), while consuming considerably less protein. In addition, the UDS method allows rapid screening of detergents for membrane protein crystallization in a fraction of the time required by SEC. Here we use the UDS method in the identification of suitable detergents and buffer compositions for the crystallization of three recombinant prokaryotic membrane proteins. The implications of our results for membrane protein crystallization prescreening are discussed.
An artificially evolved albumin binding module facilitates chemical shift epitope mapping of GA domain interactions with phylogenetically diverse albumins
Authors: He Yanan , Chen Yihong , Rozak David A. , Bryan Philip N. , Orban John
Published: June 2007

Protein G‐related albumin‐binding (GA) modules occur on the surface of numerous Gram‐positive bacterial pathogens and their presence may promote bacterial growth and virulence in mammalian hosts. We recently used phage display selection to evolve a GA domain, PSD‐1 (phage selected domain‐1), which tightly bound phylogenetically diverse albumins. With respect to PSD‐1's broad albumin binding specificity, it remained unclear how the evolved binding epitope compared to those of naturally occurring GA domains and whether PSD‐1's binding mode was the same for different albumins. We investigate these questions here using chemical shift perturbation measurements of PSD‐1 with rabbit serum albumin (RSA) and human serum albumin (HSA) and put the results in the context of previous work on structure and dynamics of GA domains. Combined, these data provide insights into the requirements for broad binding specificity in GA‐albumin interactions. Moreover, we note that using the phage‐optimized PSD‐1 protein significantly diminishes the effects of exchange broadening at the binding interface between GA modules and albumin, presumably through stabilization of a ligand‐bound conformation. The employment of artificially evolved domains may be generally useful in NMR structural studies of other protein–protein complexes.
Functional structure of the somatomedin B domain of vitronectin
Authors: Zhou Aiwu
Published: June 2007

The N‐terminal somatomedin B domain (SMB) of vitronectin binds PAI‐1 and the urokinase receptor with high affinity and regulates tumor cell adhesion and migration. We have shown previously in the crystal structure of the PAI‐1/SMB complex that SMB, a peptide of 51 residues, is folded as a compact cysteine knot of four pairs of crossed disulfide bonds. However, the physiological significance of this structure was questioned by other groups, who disputed the disulfide bonding shown in the crystal structure (Cys5–Cys21, Cys9–Cys39, Cys19–Cys32, Cys25–Cys31), notably claiming that the first disulfide is Cys5–Cys9 rather than the Cys5–Cys21 bonding shown in the structure. To test if the claimed Cys5–Cys9 bond does exist in the SMB domain of plasma vitronectin, we purified mouse and rat plasma vitronectin that have a Met (hence cleavable by cyanogen bromide) at residue 14, and also prepared recombinant human SMB variants from insect cells with residues Asn14 or Leu24 mutated to Met. HPLC and mass spectrometry analysis showed that, after cyanogen bromide digestion, all the fragments of the SMB derived from mouse or rat vitronectin or the recombinant SMB mutants are still linked together by disulfides, and the N‐terminal peptide (residue 1–14 or 1–24) can only be released when the disulfide bonds are broken. This clearly demonstrates that Cys5 and Cys9 of SMB do not form a disulfide bond in vivo, and together with other structural evidence confirms that the only functional structure of the SMB domain of plasma vitronectin is that seen in its crystallographic complex with PAI‐1.
Chemical cross‐linking of the chloroplast localized small heat‐shock protein, Hsp21, and the model substrate citrate synthase
Authors: Åhrman Emma , Lambert Wietske , Aquilina J. Andrew , Robinson Carol V. , Emanuelsson Cecilia Sundby
Published: June 2007

The molecular mechanism whereby the small heat‐shock protein (sHsp) chaperones interact with and prevent aggregation of other proteins is not fully understood. We have characterized the sHsp–substrate protein interaction at normal and increased temperatures utilizing a model substrate protein, citrate synthase (CS), widely used in chaperone assays, and a dodecameric plant sHsp, Hsp21, by chemical cross‐linking with 3,3′‐Dithiobis[sulfosuccinimidylpropionate] (DTSSP) and mass spectrometric peptide mapping. In the absence of CS, the cross‐linker captured Hsp21 in dodecameric form, even at increased temperature (47°C). In the presence of equimolar amounts of CS, no Hsp21 dodecamer was captured, indicating a substrate‐induced Hsp21 dodecamer dissociation by equimolar amounts of CS. Cross‐linked Hsp21–Hsp21 dipeptides indicated an exposure of the Hsp21 C‐terminal tails and substrate‐binding sites normally covered by the C terminus. Cross‐linked Hsp21–CS dipeptides mapped to several sites on the surface of the CS dimer, indicating that there are numerous weak and short‐lived interactions between Hsp21 and CS, even at normal temperatures. The N‐terminal arms especially interacted with a motif in the CS dimer, which is absent in thermostable forms of CS. The cross‐linking data suggest that the presence of substrate rather than temperature influences the conformation of Hsp21.
Solution structure of a membrane‐anchored ubiquitin‐fold (MUB) protein from Homo sapiens
Authors: de la Cruz Norberto B. , Peterson Francis C. , Lytle Betsy L. , Volkman Brian F.
Published: June 2007

The protein Bc059385, whose solution structure is reported here, is the human representative of a recently identified family of membrane‐anchored ubiquitin‐fold (MUB) proteins. Analysis of their similarity to ubiquitin indicates that homologous amino acid residues in MUBs form a hydrophobic surface very similar to the recognition patch surrounding Ile‐44 in ubiquitin. This suggests that MUBs may interact with proteins containing an α‐helical motif similar to those of some ubiquitin binding domains. A disordered loop common to MUBs may also provide a second protein interaction site. From the available data, it is probable that this protein is prenylated and associated with the membrane. With <20% identity to ubiquitin, the MUB family further expands the sequence space that maps to the β‐grasp fold, and adds membrane localization to its list of functional roles.
Active site geometry of glucose‐1‐phosphate uridylyltransferase
Authors: Thoden James B. , Holden Hazel M.
Published: June 2007

Glucose‐1‐phosphate uridylyltransferase, or UGPase, catalyzes the production of UDP‐glucose from glucose‐1‐phosphate and UTP. Because of the biological role of UDP‐glucose in glycogen synthesis and in the formation of glycolipids, glycoproteins, and proteoglycans, the enzyme is widespread in nature. Recently this laboratory reported the three‐dimensional structure of UGPase from Escherichia coli. While the initial X‐ray analysis revealed the overall fold of the enzyme, details concerning its active site geometry were limited because crystals of the protein complexed with either substrates or products could never be obtained. In an effort to more fully investigate the active site geometry of the enzyme, UGPase from Corynebacterium glutamicum was subsequently cloned and purified. Here we report the X‐ray structure of UGPase crystallized in the presence of both magnesium and UDP‐glucose. Residues involved in anchoring the ligand to the active site include the polypeptide chain backbone atoms of Ala 20, Gly 21, Gly 117, Gly 180, and Ala 214, and the side chains of Glu 36, Gln 112, Asp 143, Glu 201, and Lys 202. Two magnesium ions are observed coordinated to the UDP‐glucose. An α‐ and a β‐phosphoryl oxygen, three waters, and the side chain of Asp 142 ligate the first magnesium, whereas the second ion is coordinated by an α‐phosphoryl oxygen and five waters. The position of the first magnesium is conserved in both the glucose‐1‐phosphate thymidylyltransferases and the cytidylyltransferases. The structure presented here provides further support for the role of the conserved magnesium ion in the catalytic mechanisms of the sugar‐1‐phosphate nucleotidylyltransferases.
Salt Sensitivity and Hypertension in African Americans: Implications for Cardiovascular Nurses
Authors: Peters Rosalind M. , Flack John M.
Published: June 2007

Hypertension is a major public health problem in the U.S. Salt sensitivity is an important factor associated with hypertension and its complications, yet it has not been addressed in the nursing literature. Salt sensitivity is a directionally appropriate rise or fall in blood pressure when salt is added or removed, respectively. The change in blood pressure in salt‐sensitive subjects occurs to a degree exceeding random blood pressure fluctuations. Salt sensitivity is present in 30% of normotensive and over 50% of hypertensive persons. It is more prevalent among African Americans, older persons, and individuals with renal insufficiency or diabetes. This paper provides nurses with an overview of salt sensitivity and its significance in hypertension. It presents conceptual and operational definitions of salt sensitivity, identifies factors contributing to its development, and describes implications for nursing practice.
Adipokines in cord blood and risk of wheezing disorders within the first two years of life
Authors: Rothenbacher D. , Weyermann M. , Fantuzzi G. , Brenner H.
Published: June 2007

Background
Adipokines are involved in the regulation of many inflammatory processes and are present at very high concentrations in cord blood of term infants.

Objective
We analysed data of a large prospective birth cohort study to examine whether adiponectin and leptin concentration in cord blood are determinants of wheezing disorders in children within the first 2 years of life.

Methods
Seven hundred and forty mothers and their newborns were included in this analysis. Adiponectin and leptin concentrations were measured in cord blood. The cumulative incidence of physician‐reported asthma or obstructive bronchitis was recorded during a 2‐year follow‐up.

Results
During the first 2 years of life, asthma or obstructive bronchitis was reported by the caring paediatricians for 157 (19.6%) of the children. We found a strong interaction of cord blood adiponectin and history of atopic disease in the mother with respect to the risk of physician‐reported asthma or obstructive bronchitis (P=0.006). Compared with children with cord blood levels in the middle quintile (reference category), the odds ratios for physician‐reported asthma or obstructive bronchitis in the bottom quintile and top quintile were 0.14 [95% confidence interval (CI) 0.02–0.90] and 2.12 (95% CI 0.67–6.66), respectively (P for trend=0.0003), among children of mothers with a history of atopy. This association was independent of other established risk factors. Leptin levels in cord blood were not associated with risk of asthma or obstructive bronchitis.

Conclusions
In children of mothers with a history of atopy, concentrations of adiponectin in cord blood could play an important role in determining risk of wheezing disorders in early childhood.
Diagnostic accuracy of cytology and immunocytology in carcinomatous effusions
Authors: Metzgeroth G. , Kuhn C. , Schultheis B. , Hehlmann R. , Hastka J.
Published: June 2007

Background:  Immunocytology substantially improves the diagnostic accuracy of conventional cytology in the diagnosis of carcinomatous effusions. Due to the unequivocal characterization of the various cell populations, a sensitivity of 92% and specificity of 100% was achieved by immunocytology, examining samples of 1234 serous effusions.

Objective:  Cytology plays a central role in the aetiological clarification of serous effusions. The sensitivity of this method for the diagnosis of carcinomatous effusions varies between 40% and 80%. The aim of the present study was to investigate whether immunocytology substantially improves the diagnostic quality of the cytological examination in the diagnosis of carcinomatous effusions.

Method:  Consecutive serous effusions were examined by conventional cytology and by immunocytology. The immunocytological examination was performed on smears, using a standard panel of three antibodies against pancytokeratin, human epithelial antigen 125 and calretinin.

Results:  Altogether, 1234 effusion samples were examined. A total of 603 effusions were caused by carcinomas, five by malignant mesotheliomas, 11 by malignant lymphomas and 615 by non‐malignant disorders. In conventional cytology, carcinomatous effusions were correctly diagnosed in 314 samples, corresponding to a sensitivity of 52%. In 31 specimens (5%) tumour cells without further specification were described and in 161 samples (27%) the presence of tumour cells was suspected (84% overall sensitivity). A total of 97 carcinomatous effusions (16%) were diagnosed false‐negatively and 50 (8%) of the 615 non‐malignant effusions false‐positively (92% specificity). In immunocytology, 561 carcinomatous samples were correctly diagnosed, representing a sensitivity of 93%. In six cases (1%) the presence of tumour cells was suspected. A total of 36 carcinomatous effusions (6%) were diagnosed false‐negatively (94% over‐all sensitivity). Out of the 615 non‐malignant specimens, there were no false‐positive diagnoses (100% specificity).

Conclusion:  Immunocytology is a simple, cost‐effective, routinely practicable method which substantially improves the diagnostic accuracy of conventional cytology in the diagnosis of carcinomatous effusions. Therefore, we recommend the use of immunocytology in all those cases where cytology on its own is not completely unequivocal.
Effects of livestock breed and grazing intensity on biodiversity and production in grazing systems. 4. Effects on animal diversity
Authors: Wallis De Vries M. F. , Parkinson A. E. , Dulphy J. P. , Sayer M. , Diana E.
Published: June 2007

Finding an optimal balance between livestock production and grazing impact on animal diversity is important for the development of sustainable grazing systems. This paper tests the hypothesis that extensification of grazing management enhances animal diversity. Similar treatments were applied over a period of three years to sites in the UK, France, Germany and Italy. There were three treatments at each site: moderate grazing intensity with a commercial breed (MC), lenient grazing intensity with a commercial breed (LC) and lenient grazing intensity with a traditional breed (LT). Animal diversity was studied at the species level for birds, hares, butterflies and grasshoppers, and at higher taxonomic level for ground‐dwelling arthropods. Bird and hare numbers were low and showed no overall treatment effects. Species richness and abundance of butterflies and grasshoppers were higher for treatment LC than for treatment MC, both for species preferring short open grasslands and those preferring tall grasslands. There was no difference in the impact of commercial or traditional breeds. Most ground‐dwelling arthropod groups did not show consistent treatment effects but some taxa showed site‐specific responses, generally indicating a greater abundance at lenient grazing intensity. Overall, the study showed that lenient grazing intensity enhanced animal diversity on grasslands at a small scale within 3 years. By comparison, the effect of livestock breed differences was negligible. Follow‐up research is needed to elucidate the processes leading to increased biodiversity in patch mosaics and to establish the generality of these findings at larger spatial scales and longer time scales.
Effects of livestock breed and grazing intensity on biodiversity and production in grazing systems. 1. Nutritive value of herbage and livestock performance
Authors: Isselstein J. , Griffith B. A. , Pradel P. , Venerus S.
Published: June 2007

Reduction of grazing intensity and the use of traditional instead of commercial breeds has frequently been recommended to meet biodiversity and production goals in sustainable grazing systems in Europe. To test the impact of such practices across a range of contrasting grassland types, integrated measurements of foraging behaviour, agronomic production and botanical, structural and invertebrate biodiversity were made over three years on four sites in the UK, Germany, France and Italy. The sites in the UK and Germany were mesotrophic grassland with high productivity and low to moderate initial levels of plant diversity, and were grazed by cattle. The French site was a semi‐natural, species‐rich grassland grazed by cattle. The Italian site contained a wider range in plant diversity, from species‐rich to mesotrophic grassland, and was grazed by sheep. The treatments were: MC, moderate grazing intensity with a commercial breed – this was designed to utilize herbage growth for optimum livestock production; LC, lenient grazing intensity with a commercial breed – this was designed to increase biodiversity by not fully utilizing herbage growth; and LT, lenient grazing intensity with a traditional breed – this was also designed to increase biodiversity. Neither fertilizers nor pesticides were applied. The nutritive value of the herbage and the performance of the livestock were measured. Mean stocking rates were proportionately 0·30–0·40 lower and mean sward heights and herbage mass on offer were 0·30–0·50 higher on the LC and LT treatments compared with the MC treatment. The proportion of live and dead material, and leaves and stems in the herbage, its chemical composition and nutritive value were little affected by the treatments. Individual livestock performance, measured as liveweight gain, showed no consistent response to treatment. In Germany, performance on the MC treatment was slightly lower than on the LC and LT treatments but no such difference was found on the sites in the other countries. Livestock breed did not have a strong effect on livestock performance. In the UK and France the traditional breeds had a lower performance but this was not the case in Germany or Italy. Livestock performance per ha of the LC and LT treatments was up to 0·40 lower than of the MC treatment. It is concluded that biodiversity‐targeted extensive grazing systems have potential to be integrated into intensive livestock production systems because the individual livestock performance reaches a similar level compared to a moderate grazing intensity. Traditional breeds did not have a production advantage over commercial breeds on extensively managed pastures.
Climate change and grasslands through the ages: an overview
Authors: ’t Mannetje L.
Published: June 2007

Change from cool to warm temperatures and vice versa have occurred throughout geological time. During the Jurassic and Cretaceous periods (206–65 million years ago, Ma) the climate was more uniformly warm and moist than at present and tropical rainforests were widespread. Grasses evolved during the Jurassic period and they expanded greatly as the climate differentiated with reduced rainfall and temperatures. C4‐grasses probably arose during the Oligocene period (24–35 Ma). During the Miocene period (23·8–5·3 Ma) grasslands expanded into huge areas (e.g. prairies in the USA, steppe in Eurasia, and pampas and llanos in South America). During the Quaternary period (1·8 Ma till now) some twenty‐two different ice ages with periodicities of about 100 000 years occurred. Eighteen‐thousand years ago, north‐western Europe had a polar climate with tundra vegetation and the Mediterranean region was covered by steppe. During that time Amazonia was so dry that it was covered in extensive areas of savanna and the Sahara expanded rapidly. Only in the last 10 000 years has a closed rainforest covered the Amazonian region again. However, 9000 years ago a brief period of global warming caused excessive rains, which caused the sea and river levels to rise in north‐western Europe with tremendous loss of life. The present period of extreme dryness in the Sahara only started some 5000 years ago and then the desert expanded rapidly into the Sahel. Before that the Sahara was covered by steppe. Global warming took place between about ad 900 and about ad 1200 or 1300 just before the Little Ice Age (1550–1700 ad). The article concludes with a description of temperature and vegetation changes that are occurring in Europe at present. It is predicted that C4‐grasses, which are already present in southern Europe, will further expand but that, in the short term, land abandonment will have much more deleterious effects than temperature change due to increased wild fires, loss of biodiversity and desertification.
Temperate grasslands and global atmospheric change: a review
Authors: Soussana J‐F. , Lüscher A.
Published: June 2007

Recent reviews confirm and extend previous observations that elevated carbon dioxide (CO2) concentrations stimulate photosynthesis, leading to increased plant productivity. Elevated CO2concentrations tend to reduce the sensitivity of grassland ecosystems to low levels of precipitation but induce progressive nitrogen (N) limitations on plant growth which can be alleviated by supplying a significant external input of N in the form of mineral fertilizer or through the increased use of N‐fixing legumes. Other nutrients, such as phosphorus, can act as the main limiting factor restricting the growth response in legumes to atmospheric CO2concentration. The botanical composition of temperate grasslands is affected by the rise in atmospheric CO2concentration, possibly through a decline in the relative abundance of grasses. Elevated CO2concentration will also alter the feeding value of herbage to grazers both in terms of fine‐scale (for example, crude protein concentration and C:N ratio) and coarse‐scale (legumes vs. grasses and C3‐ vs. C4‐species) changes. The management guidelines of grasslands will need to be adapted to global atmospheric and climatic changes and to increased variability in climate.
Effects of livestock breed and grazing intensity on grazing systems: 3. Effects on diversity of vegetation
Authors: Scimone M. , Rook A. J. , Garel J. P. , Sahin N.
Published: June 2007

Finding an optimal balance between livestock production and grazing impact on plant biodiversity is an important issue in the design of grazing systems. This paper describes a study of the effect of two levels of grazing intensity combined with different animal breeds on plant biodiversity and sward structural diversity of semi‐natural grasslands conducted over 3 years in the United Kingdom (UK), France (F), Germany (D) and Italy (I). There were three treatments at each site: moderate grazing intensity with a commercial breed (MC), lenient grazing intensity with a commercial breed (LC) and lenient grazing intensity with a traditional breed (LT). Grazing livestock were cattle in the UK, F and D, and sheep in I. Only grazing intensity had clear effects on vegetation diversity, the effects depending on site‐specific vegetation characteristics. In more diverse pastures with finer scale heterogeneity in F and I, there was little effect of the treatments. In less diverse swards with higher grass dominance and coarse‐scale heterogeneity, the number of species decreased from initial levels on the lenient grazing intensity treatments (treatments LC and LT), because of increased dominance of grasses reducing the cover of other species, particularly legumes. The structural diversity of the pastures was more affected by level of grazing intensity than botanical diversity. In more diverse, semi‐natural grasslands, structural heterogeneity was not affected by the treatments. In less diverse, more productive swards, structural heterogeneity decreased where large patches were initially found on the UK site, and increased where smaller patches were initially found on the D site. It is concluded that management systems to conserve diversity need to consider carefully the background environment, and that more knowledge of the mechanisms involved is needed at farm and landscape scales.
The immune response during a Strongyloides ratti infection of rats
Authors: WILKES C. P , BLEAY C. , PATERSON S. , VINEY M. E.
Published: June 2007

A range of immune parameters was measured during a primary infection of Strongyloides ratti in its natural rat host. The immune parameters measured were interleukin‐4 (IL‐4) and interferon‐γ from both the spleen and mesenteric lymph node (MLN) cells; parasite‐specific immunoglobulin G1(IgG1), IgG2a and IgG2b in serum and in intestinal tissue; parasite‐specific IgG and total IgE in serum; parasite‐specific and total IgA in intestinal tissue and rat mast cell protease II in intestinal tissue. Parasite‐specific IgG1, IgG2a and total IgE in serum and parasite‐specific IgA and rat mast cell protease II in intestinal tissue all occurred at significantly greater concentrations in infected animals, compared with non‐infected animals. Similarly, the production of IL‐4 by MLN cells stimulated with parasitic female antigen or concanavalin A occurred at significantly greater concentrations in infected animals, compared with non‐infected animals. In all, this suggests that there is a T‐helper 2‐type immune response during a primary S. ratti infection. These data also show the temporal changes in these components of the host immune response during a primary S. ratti infection.
Tumour necrosis factor α contributes to protection against Giardia lamblia infection in mice
Authors: ZHOU P. , LI E. , SHEA‐DONOHUE T. , SINGER S. M.
Published: June 2007

Giardia lamblia is a ubiquitous parasite that causes diarrhoea. Effective control of Giardia infections in mice has been shown to involve IgA, T cells, mast cells and IL‐6. We now show that Tumour necrosis factor α (TNFα) also plays an important role in the early control of giardiasis. Mice treated with neutralizing anti‐TNFα antibodies or genetically deficient in TNFα were infected with the G. lamblia clone GS/(M)‐H7. In both cases, mice lacking TNFα had much higher parasite numbers than controls during the first 2 weeks of infections. However, anti‐parasite IgA levels, mast cell responses, and IL‐4 and IL‐6 mRNA levels do not appear significantly altered in the absence of TNFα. In addition, we show that mice infected with G. lamblia exhibit increased intestinal permeability, similar to human Giardia infection, and that this increase occurs in both wild‐type and TNFα deficient mice. We conclude that TNFα is essential for host resistance to G. lamblia infection, and that it does not exert its effects through mechanisms previously implicated in control of this parasite.
Modelling advection and diffusion of water isotopologues in leaves
Authors: CUNTZ MATTHIAS , OGÉE JÉRÔME , FARQUHAR GRAHAM D. , PEYLIN PHILIPPE , CERNUSAK LUCAS A.
Published: June 2007

We described advection and diffusion of water isotopologues in leaves in the non‐steady state, applied specifically to amphistomatous leaves. This explains the isotopic enrichment of leaf water from the xylem to the mesophyll, and we showed how it relates to earlier models of leaf water enrichment in non‐steady state. The effective length or tortuosity factor of isotopologue movement in leaves is unknown and, therefore, is a fitted parameter in the model. We compared the advection–diffusion model to previously published data sets for Lupinus angustifolius and Eucalyptus globulus. Night‐time stomatal conductance was not measured in either data set and is therefore another fitted parameter. The model compared very well with the observations of bulk mesophyll water during the whole diel cycle. It compared well with the enrichment at the evaporative sites during the day but showed some deviations at night for E. globulus. It became clear from our analysis that night‐time stomatal conductance should be measured in the future and that the temperature dependence of the tracer diffusivities should be accounted for. However, varying mesophyll water volume did not seem critical for obtaining a good prediction of leaf water enrichment, at least in our data sets. In addition, observations of single diurnal cycles do not seem to constrain the effective length that relates to the tortuosity of the water path in the mesophyll. Finally, we showed when simpler models of leaf water enrichment were suitable for applications of leaf water isotopes once weighted with the appropriate gas exchange flux. We showed that taking an unsuitable leaf water enrichment model could lead to large biases when cumulated over only 1 day.
Plastid tRNA Genes trnC‐GCA and trnN‐GUU are essential for plant cell development
Authors: Legen Julia , Wanner Gerhard , Herrmann Reinhold G. , Small Ian , Schmitz‐Linneweber Christian
Published: June 2007

Higher plant chloroplast genomes code for a conserved set of 30 tRNAs. This set is believed to be sufficient to support translation, although import of cytosolic tRNA has been proposed to provide additional tRNA species to the chloroplast. Previous knock‐outs of tRNA genes, or the pronounced reduction of the level of selected tRNAs, has not led to severe phenotypes. We deleted the two tRNA genes trnN‐GUU and trnC‐GCA independently from the plastid chromosome of tobacco. No homoplastomic tissue of either ΔtrnN or ΔtrnC plants could be isolated. Both mutants exhibit occasional loss of leaf sectors, and mutant plastid chromosomes are rapidly lost upon relief of selective pressure. This suggests that the knock‐out of both trn genes is lethal, and that both tRNA species are required for cell survival. Surprisingly, the impact on chloroplast and cell development differs pronouncedly between the two mutants. Heteroplastomic ΔtrnC and ΔtrnN tissue exhibit different aberrations of the internal membrane systems and, more importantly, heteroplastomic ΔtrnN plants are variegated. Accumulation of tRNA‐N and plastid‐encoded proteins is reduced in white sectors of ΔtrnN plants, and differentiation of palisade cells is abolished. Our data demonstrate that plastid tRNAs are essential, i.e. not complemented by cytosolic tRNA, and have a differential impact on chloroplast and plant cell development.
Practical application of the virtual crossmatch
Authors: Zangwill Steven , Ellis Thomas , Stendahl Gail , Zahn Amy , Berger Stuart , Tweddell James
Published: June 2007

Abstract:  Background: HLA antibody sensitization is a risk factor for morbidity and mortality following heart transplantation. We previously reported the results of our in vitro study demonstrating the predictive value of the Virtual Crossmatch (VXM) and have since applied it clinically for sensitized children listed for heart transplant at our center. The VXM utilizes the results of specific antibody screening via flow cytometry to predict acute incompatibility. This review examines the effect of the VXM on wait times and outcomes. Methods: The study population included all patients listed for heart transplantation at Children's Hospital of Wisconsin. Antibody sensitization was defined as PRA > 10% and/or by the identification of HLA specific antibody using AHG‐CDC or flow cytometry. Categorical data was analyzed via Fisher's exact test while continuous variables were compared via an unpaired t test. Results: There were a total of 111 listed patients between 7/91 – 9/06. The sensitization rate was 23% (25/111). 19 patients who went on to transplant, deterioration or death were divided into 3 groups depending on listing strategy; Group 1 were listed with a prospective crossmatch requirement, Group 2 with a VXM, and Group 3 with a retrospective cross match. 7/8 patients in group 1 died prior to transplant with median wait time of 119 days. 9/10 patients in group 2 were transplanted with 100% survival and median wait time of 65 days, Group 3 included 1 patient who received a graft after 54 days and died 3 months post transplant with humoral rejection. The VXM was highly concordant with the retrospective crossmatch. Conclusions: Use of a VXM can lead to shorter wait times and better outcomes as a listing strategy for sensitized children requiring cardiac transplantation. The VXM allows transplant physicians to risk stratify patients and consider an anticipated positive crossmatch as one additional factor in the risk‐benefit analysis inherent to any donor offer. This experience supports use of the VXM as an alternative to prospective crossmatch requirements. One should recognize that other era dependent improvements such as updated criteria for patient and donor selection along with newer therapies and bridging options may have contributed to superior outcomes seen in the more recent cohort of patients treated with the VXM approach.
Partial host fidelity in nest selection by the shiny cowbird (Molothrus bonariensis), a highly generalist avian brood parasite
Authors: MAHLER B. , CONFALONIERI V. A. , LOVETTE I. J. , REBOREDA J. C.
Published: June 2007

Obligate avian brood parasites can be host specialists or host generalists. In turn, individual females within generalist brood parasites may themselves be host specialists or generalists. The shiny cowbirdMolothrus bonariensisis an extreme generalist, but little is known about individual female host fidelity. We examined variation in mitochondrial control region sequences from cowbird chicks found in nests of four common Argentinean hosts. Haplotype frequency distributions differed among cowbird chicks from nests of these hosts, primarily because eggs laid in nests of house wrensTroglodytes aedondiffered genetically from those laid in nests of the other three hosts (chalk‐browed mockingbirdMimus saturninus, brown‐and‐yellow marshbirdPseudoleistes virescens, and rufous‐collared sparrowZonotrichia capensis). These differences in a maternally inherited marker indicate the presence of a nonrandom laying behaviour in the females of this otherwise generalist brood parasite, which may be guided by choice for nest type, as house wrens nest in cavities whereas the other three species are open cup nesters.
Personality Change Influences Mortality in Older Men
Authors: Mroczek Daniel K. , Spiro Avron
Published: June 2007

Previous studies have indicated that high neuroticism is associated with early mortality. However, recent work suggests that people's level of neuroticism changes over long periods of time. We hypothesized that such changes in trait neuroticism affect mortality risk. Growth-curve parameters (levels and slopes) that quantified the trajectories of neuroticism change over 12 years were used to predict 18-year risk of mortality among 1,663 aging men. Proportional hazards models were used to estimate mortality risk from level and slope parameters, controlling for objective and subjective health, depression, and age. Although a parallel analysis of extraversion showed no significant effects, level and slope of neuroticism interacted in their effect on mortality. Men who had both a high average level of neuroticism and an increasing level of neuroticism over time had much lower survival than men without that combination. These findings suggest that it is not just the level of personality traits, but their direction of change, that is related to mortality.
The Art of Conversation Is Coordination
Authors: Richardson Daniel C. , Dale Rick , Kirkham Natasha Z.
Published: June 2007

When two people discuss something they can see in front of them, what is the relationship between their eye movements? We recorded the gaze of pairs of subjects engaged in live, spontaneous dialogue. Cross-recurrence analysis revealed a coupling between the eye movements of the two conversants. In the first study, we found their eye movements were coupled across several seconds. In the second, we found that this coupling increased if they both heard the same background information prior to their conversation. These results provide a direct quantification of joint attention during unscripted conversation and show that it is influenced by knowledge in the common ground.
Rapid Word Learning Under Uncertainty via Cross-Situational Statistics
Authors: Yu Chen , Smith Linda B.
Published: June 2007

There are an infinite number of possible word-to-word pairings in naturalistic learning environments. Previous proposals to solve this mapping problem have focused on linguistic, social, representational, and attentional constraints at a single moment. This article discusses a cross-situational learning strategy based on computing distributional statistics across words, across referents, and, most important, across the co-occurrences of words and referents at multiple moments. We briefly exposed adults to a set of trials that each contained multiple spoken words and multiple pictures of individual objects; no information about word-picture correspondences was given within a trial. Nonetheless, over trials, subjects learned the word-picture mappings through cross-trial statistical relations. Different learning conditions varied the degree of within-trial reference uncertainty, the number of trials, and the length of trials. Overall, the remarkable performance of learners in various learning conditions suggests that they calculate cross-trial statistics with sufficient fidelity and by doing so rapidly learn word-referent pairs even in highly ambiguous learning contexts.
Explaining Developmental Reversals in False Memory
Authors: Brainerd C.J. , Reyna V.F.
Published: June 2007

We report the first demonstration that a simple, theory-driven manipulation produces opposite developmental trends in false memory for the same information. When 6-, 10-, and 14-year-olds studied lists containing exemplars of familiar taxonomic categories, false memory for the same unpresented items (category exemplars and labels) increased with age if list items were semantically related but decreased with age if semantic relations could not be formed among list items. A control experiment ruled out the hypothesis that these results were due to young children having generic deficits in forming relations among list items.
Regulation Crisis: Evaluating the Potential Legitimizing Effects of “Corporate Manslaughter” Cases
Authors: ALMOND PAUL
Published: June 2007

This article identifies a new direction for discussion of the proposed “corporate manslaughter” offense. Considering work‐related fatality cases with reference to the concept of legitimacy allows us to obtain a fuller understanding of their importance and the potential benefits associated with reform of the law. Work‐related fatality cases have inherent power as “signal offenses.” A failure to resolve these cases in a manner that satisfies the interests of the “publics” that the Health and Safety Executive (HSE) faces, may lead to a crisis of legitimacy for the agency. Reforming the law so as to facilitate such a response may offer important legitimatory benefits to regulators.
Assessing Need in the United States, Germany, and Sweden: The Organization of Welfare Casework and the Potential for Responsiveness in the “Three Worlds”
Authors: JEWELL CHRISTOPHER J.
Published: June 2007

An ongoing challenge for the administrative state is balancing the programmatic values of responsiveness and accountability. Few studies have examined these policy issues cross‐nationally for social assistance, a needs‐based form of income support where these tensions are especially significant. Based on street‐level case studies, this article demonstrates persistent diversity among welfare states in how these programmatic tradeoffs are made, contrasting a U.S. approach that emphasizes programmatic control via a bureaucratic, flat‐grant system, with German and Swedish programs in which individualized assessments of need are a core organizational task. In each European case, legal frameworks, expertise, and work arrangements have evolved in nationally specific ways to contend with the challenges frontline discretion poses to program integrity.
Effects of The Remote C Fibres Stimulation Induced by Capsaicin on the Blink Reflex in Chronic Migraine
Authors: Tommaso M de , Sardaro M , Pecoraro C , fruscolo O Di , Serpino C , Lamberti P , Livrea P
Published: June 2007

The aim of this study was to test the function of the diffuse noxious inhibitory control system (DNIC) in chronic and episodic migraine, exploring the blink reflex (BR) modifications induced by topical application of capsaicin on the hand. We evaluated 11 migraine without aura (MA) and nine chronic migraine (CM) patients during the not symptomatic phase; they were compared with 14 non-headache subjects (N). The BR was elicited by weak electrical stimuli delivered to the right supraorbital nerve; it was obtained 10 min and 20 min after the application of 1 ml of 3% capsaicin in a cream base (Teofarma) on the skin of the dorsum of the right hand, and 60 min after capsaicin removal. The subjective pain sensation induced by capsaicin was significantly increased in CM with respect to both MA patients and normal subjects; the R2 area was increased in CM patients during capsaicin application, with respect to controls and MA patients, who did not exhibit any reflex alterations. These results may suggest a failure of DNIC and a disturbed control of the trigeminal reflex at the central level, linked with migraine frequency.
The rhetoric of public diplomacy and propaganda wars: A view from self‐presentation theory
Authors: MOR BEN D.
Published: June 2007

Abstract. Efforts by governments to affect foreign public opinion through direct communication – and in competition with rival governments – have been a stable and consistent feature of international diplomacy since the turn of the twentieth century. Yet public diplomacy and its use in propaganda wars has not been sufficiently theorized, a lacuna that this article seeks to address by means of the social‐psychological theory of self‐presentation and impression management. The discussion suggests that public diplomacy is a form of self‐presentation for social empowerment, in which rhetorical strategies and associated tactics are means of addressing image predicaments in foreign public opinion. The analysis is illustrated by means of the recent Israeli‐Palestinian conflict and its presentation in the official websites of the parties.
What Do Dragons Think About in their Dark Lonely Caves? [1] or Critical Studies: The Importance of Knowledge
Authors: BANCROFT ALISON
Published: June 2007

Increasing numbers of Critical Studies publications are currently reaching the market, with teachers receiving numerous advertising materials and catalogues to persuade them to buy. This paper considers the content and approach of some of these materials, with particular reference to the teaching packs, and examines some of the issues that the decisions embodied in these publications raise for art teachers and for Critical Studies teaching.

The orthodoxies that would seem to be developing are worrying, and rigorous debate is needed to expose and explore the grounds on which categories of inclusion and exclusion are constructed. It is argued that such debate needs to be underpinned by knowledge of the paradigms in operation, and that access to such knowledge is essential, for both teachers and students, if Critical Studies is not to degenerate into imaginative speculation or indoctrination.
The Impact of Modularity and Credit Accumulation on Undergraduate Art and Design Education
Authors: BUSS DAVID
Published: June 2007

Credit Accumulation and modular structures now account for the majority of undergraduate provision in art and design in the UK. This shift away from traditional structures has gained momentum during the past three years and is part of a national move towards credit accumulation and modularity from GCSE through to Masters level work in all subjects.

The origins and rationale for these structures are outlined and their advantages are discussed with particular reference to art and design in Higher Education, together with their implications for teaching methods, for student learning, and for assessment. These points are illustrated with examples of new developments in the sector. The author responds to some of the reservations voiced by critics of CATS and Modularity and argues that these structures are more appropriate to the needs and ambitions of students in the 1990s.
Pedagogy and the Poetic: A Moment of Recognition
Authors: MACLEOD KATY
Published: June 2007

This paper is concerned with pedagogic form and voice. It references a particular pedagogy and the means by which this has and can be represented through a research process. I define this research process as poetic because I need to convey the profoundly creative process of pedagogies entered into by women (and some men), whose creative process is their teaching and hence their poetic form.
Understanding Art
Authors: MESSON PHILIP
Published: June 2007

The new curriculum in art establishes two elements in the study of the subject in schools; one active, a doing and making element, and one more cerebral not necessarily involving the making of works of art. This second element has been designated ‘knowledge and understanding’ and ideally should be related to the practical activities in the classroom, but it raises the question how understanding is achieved in art and what form such understanding might take.

So far as knowledge is concerned the matter is fairly straightforward for it is easier to itemise the things that can be known about art. With ‘understanding’, however, we have to ask how it might be judged or recognised; how it might manifest itself. Does it manifest itself in discussion about works of art, or in the making of works of art, or are there other phenomena which might indicate the presence of understanding?