bluuebunny/crossref_metadata_2025 huggingface dataset:
Biological characterization of the zinc site coordinating histidine residues of staphylococcal enterotoxin C2
Authors: Wang Xiaogang , Zhang Huiwen , Xu Mingkai , Cai Yongming , Liu Changxiao , Su Zhencheng , Zhang Chenggang
Published: February 2009

The bacterial toxin staphylococcal enterotoxin C2 (SEC2) can cause staphylococcal toxic shock syndrome and food poisoning. Although the previously determined crystal structure of SEC2 revealed that some histidine residues (His47, His118 and His122) contribute to the binding of zinc ions, little is known about their biological roles in SEC2. This prompted us to investigate the role of the zinc site coordinating histidine residues in the biological activities of SEC2. The mutants with substitutions at positions 118 and 122 all retained T-cell stimulatory activity, whereas the histidine mutants at position 47 were defective in the ability to stimulate T-cell proliferation. Further toxicity assaysin vivoindicated that mutants SEC2-H118A and SEC2-H122A were defective in emetic and febrile activities. However, mutant SEC2-H47A could cause significant emetic and febrile responses in comparison with the other two histidine mutants. These findings suggested that the zinc-coordinating histidine residues play significant roles in superantigen and toxic activities of SEC2 and further implied that superantigen and febrile activities could be separable in staphylococcal enterotoxins. The results also show that it should be possible to design new SEC2 immunotherapeutic agents that have superantigen activity and low toxicity.
Immune evasion by Staphylococcus aureus conferred by iron-regulated surface determinant protein IsdH
Authors: Visai Livia , Yanagisawa Naoko , Josefsson Elisabet , Tarkowski Andrej , Pezzali Ilaria , Rooijakkers Suzan H. M. , Foster Timothy J. , Speziale Pietro
Published: February 2009

The ability ofStaphylococcus aureusto avoid innate immune responses including neutrophil-mediated phagocytosis is crucial for the organism to cause infection. This multifactorial process involves several secreted and cell-surface-associated proteins. In this paper we report a novel mechanism of combating neutrophils that involves iron-regulated surface determinant protein H (IsdH). The IsdH protein is part of a complex that is only expressed under iron-restricted conditions in order to bind haemoglobin and extract and transport haem into the cytoplasm. A null mutant defective in expression of IsdH, and mutants expressing variants of IsdH with substitutions in residues predicted to be involved in ligand binding, were generated fromS. aureus8325-4. The IsdH-defective mutants were shown by several measures to have reduced virulence compared with the wild-type. The mutant was engulfed more rapidly by human neutrophils in the presence of serum opsonins, survived poorly in fresh whole human blood and was less virulent in a mouse model of sepsis. The protective mechanism seems to stem from an accelerated degradation of the serum opsonin C3b.
Global networks of functional coupling in eukaryotes from comprehensive data integration
Authors: Alexeyenko Andrey , Sonnhammer Erik L.L.
Published: February 2009

No single experimental method can discover all connections in the interactome. A computational approach can help by integrating data from multiple, often unrelated, proteomics and genomics pipelines. Reconstructing global networks of functional coupling (FC) faces the challenges of scale and heterogeneity—how to efficiently integrate huge amounts of diverse data from multiple organisms, yet ensuring high accuracy. We developed FunCoup, an optimized Bayesian framework, to resolve these issues. Because interactomes comprise functional coupling of many types, FunCoup annotates network edges with confidence scores in support of different kinds of interactions: physical interaction, protein complex member, metabolic, or signaling link. This capability boosted overall accuracy. On the whole, the constructed framework was comprehensively tested to optimize the overall confidence and ensure seamless, automated incorporation of new data sets of heterogeneous types. Using over 50 data sets in seven organisms and extensively transferring information between orthologs, FunCoup predicted global networks in eight eukaryotes. For the Ciona intestinalis network, only orthologous information was used, and it recovered a significant number of experimental facts. FunCoup predictions were validated on independent cancer mutation data. We show how FunCoup can be used for discovering candidate members of the Parkinson and Alzheimer pathways. Cross-species pathway conservation analysis provided further support to these observations.
The ikaite-to-vaterite transformation: new evidence from diffraction and imaging
Authors: Tang C. C. , Thompson S. P. , Parker J. E. , Lennie A. R. , Azough F. , Kato K.
Published: February 2009

Vaterite is one of three polymorphs of calcium carbonate (CaCO3) found in nature, the others being calcite and aragonite. Here the formation of vaterite from decomposition of ikaite (CaCO3·6H2O) was investigated using synchrotron powder diffraction and scanning electron microscopy. The crystallite sizes of vaterite (∼40 nm) were found to be much smaller than those of the precursor ikaite (∼0.5–1.0 µm) as a result of vaterite nucleating as ikaite dehydrates. The rate of decomposition to vaterite increases with temperature, indicating kinetic control of this transformation. It is postulated that the structural arrangement of the hydration sphere around Ca2+in ikaite determines the orientation of Ca2+and CO32−ions such that vaterite nucleates upon dehydration. This implies that the dehydration of a precursor hydrated phase such as ikaite is required for vaterite nucleation.
Anomeric effect for a 2,5,7-triazabicyclo[2.2.1]heptane derivative
Authors: Taheri Amir , Moosavi Sayed Mojtaba
Published: February 2009

A new member of the polyazapolycyclic family of compounds, namelyN3,N6,2,5,7-pentaphenyl-2,5,7-triazabicyclo[2.2.1]heptane-3,6-diamine xylene solvate, C34H31N5·C8H10, was synthesized for the first time and the crystal structure is reported. There are no hydrogen bonds joining the molecules. All four chiral C atoms have the same absolute configurations. With regard to the four N—C—N groups, anomeric effects are observed to cause a reduction of C—N bond length and N-atom pyramidality.
A three-dimensional hydrogen-bonded network in bis(4-hydroxyanilinium) selenate(VI) dihydrate
Authors: Janczak Jan , Perpétuo Genivaldo Julio
Published: February 2009

The title compound, 2C6H8NO+·SeO42−·2H2O, contains 4-hydroxyanilinium cations, selenate(VI) anions and water molecules. One of the two independent cations is nearly planar (excluding the ammonium H atoms), while the other is markedly nonplanar, with the hydroxy and ammonium groups displaced from the plane of the benzene ring. This results from the antiparallel orientation of the cations, which interact through oppositely polarized ammonium and hydroxy groups. Ionic and hydrogen-bonding interactions join the oppositely charged units into a three-dimensional network. This work demonstrates the usefulness of 4-aminophenol in the crystal engineering of organic–inorganic hybrid compounds.
Cellular distributions of molecules with altered expression specific to thyroid proliferative lesions developing in a rat thyroid carcinogenesis model
Authors: Woo Gye‐Hyeong , Takahashi Miwa , Inoue Kaoru , Fujimoto Hitoshi , Igarashi Katsuhide , Kanno Jun , Hirose Masao , Nishikawa Akiyoshi , Shibutani Makoto
Published: February 2009

To identify differentially regulated molecules related to early and late stages of tumor promotion in a rat two‐stage thyroid carcinogenesis model by an antithyroid agent, sulfadimethoxine, microarray‐based microdissected lesion‐specific gene expression profiling was carried out. Proliferative lesions for profiling were divided into two categories: (i) focal follicular cell hyperplasias (FFCH) and adenomas (Ad) as early lesions; and (ii) carcinomas (Ca) as more advanced. In both cases, gene expression was compared with that in surrounding non‐tumor follicular cells. Characteristically, upregulation of cell cycle‐related genes in FFCH + Ad, downregulation of genes related to tumor suppression and transcription inhibitors of inhibitor of DNA binding (Id) family proteins in Ca, and upregulation of genes related to cell proliferation and tumor progression in common in FFCH + Ad and Ca, were detected. The immunohistochemical distributions of molecules included in the altered expression profiles were further examined. In parallel with microarray data, increased localization of ceruloplasmin, cyclin B1, and cell division cycle 2 homolog A, and decreased localization of poliovirus receptor‐related 3 and Id3 were observed in all types of lesion. Although inconsistent with the microarray data, thyroglobulin immunoreactivity appeared to reduce in Ca. The results thus suggest cell cycling facilitation by induction of M‐phase‐promoting factor consisting of cyclin B1 and cell division cycle 2 homolog A and generation of oxidative responses as evidenced by ceruloplasmin accumulation from an early stage, as well as suppression of cell adhesion involving poliovirus receptor‐related 3 and inhibition of cellular differentiation regulated by Id3. Decrease of thyroglobulin in Ca may reflect dedifferentiation with progression. (Cancer Sci 2009; 100: 617–625)
Stanniocalcin 2 overexpression in castration‐resistant prostate cancer and aggressive prostate cancer
Authors: Tamura Kenji , Furihata Mutsuo , Chung Su‐Yong , Uemura Motohide , Yoshioka Hiroki , Iiyama Tatsuo , Ashida Shingo , Nasu Yasutomo , Fujioka Tomoaki , Shuin Taro , Nakamura Yusuke , Nakagawa Hidewaki
Published: February 2009

Prostate cancer is usually androgen‐dependent and responds well to androgen ablation therapy based on castration. However, at a certain stage some prostate cancers eventually acquire a castration‐resistant phenotype where they progress aggressively and show very poor response to any anticancer therapies. To characterize the molecular features of these clinical castration‐resistant prostate cancers, we previously analyzed gene expression profiles by genome‐wide cDNA microarrays combined with microdissection and found dozens of trans‐activated genes in clinical castration‐resistant prostate cancers. Among them, we report the identification of a new biomarker, stanniocalcin 2, as an overexpressed gene in castration‐resistant prostate cancer cells. Real‐time polymerase chain reaction and immunohistochemical analysis confirmed overexpression of stanniocalcin 2, a 302‐amino‐acid glycoprotein hormone, specifically in castration‐resistant prostate cancer cells and aggressive castration‐naïve prostate cancers with high Gleason scores (8–10). The gene was not expressed in normal prostate, nor in most indolent castration‐naïve prostate cancers. Knockdown of stanniocalcin 2 expression by short interfering RNA in a prostate cancer cell line resulted in drastic attenuation of prostate cancer cell growth. Concordantly, stanniocalcin 2 overexpression in a prostate cancer cell line promoted prostate cancer cell growth, indicating its oncogenic property. These findings suggest that stanniocalcin 2 could be involved in aggressive phenotyping of prostate cancers, including castration‐resistant prostate cancers, and that it should be a potential molecular target for development of new therapeutics and a diagnostic biomarker for aggressive prostate cancers. (Cancer Sci 2009; 100: 914–919)
Overexpression of EIF‐5A2 predicts tumor recurrence and progression in pTa/pT1 urothelial carcinoma of the bladder
Authors: Luo Jun‐Hang , Hua Wen‐Feng , Rao Hui‐Lan , Liao Yi‐Ji , Kung Hsiang‐Fu , Zeng Yi‐Xin , Guan Xin‐Yuan , Chen Wei , Xie Dan
Published: February 2009

The authors investigated the status of abnormalities of eIF‐5A2 gene in superficial (pTa/pT1) urothelial carcinoma of the bladder (UC), as well as its correlation with clinicopathologic variables and patient outcome. The methods of immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), reverse transcription‐polymerase chain reaction (RT‐PCR) and Wetern blotting were utilized to examine protein/mRNA(messenger RNA) expression and amplification of eIF‐5A2 in a cohort of pTa/pT1 UCs. Overexpression of EIF‐5A2 was examined by IHC in 38/112 (33.9%) pTa/pT1 UCs. A significant association of overexpression of EIF‐5A2 with shortened UC patient recurrence‐free survival (P = 0.002), as well as with shortened progression‐free survival (P = 0.004), was demonstrated. Importantly, multivariate Cox regression analysis revealed that EIF‐5A2 expression provided a significant independent prognostic parameter either in tumor recurrence (P = 0.002) or in tumor progression (P = 0.007). FISH results demonstrated that eIF‐5A2 amplification was detected in 5/59 of the informative UCs; in each of the five cases with eIF‐5A2 amplification, overexpression of EIF‐5A2 was observed. In the remaining 54 UCs without eIF‐5A2 amplification, 16 cases were also observed to have overexpression of EIF‐5A2. In 13 pairs of UC and adjacent normal tissues, eight UCs were examined and showed up‐regulated eIF‐5A2 mRNA by RT‐PCR, while increased expression of EIF‐5A2 protein was only detected in 4/8 UCs by Western blotting. These findings suggest that overexpression of EIF‐5A2, as detected by IHC, may predict tumor recurrence and progression in pTa/pT1 UC patients, and the protein expression of eIF‐5A2 might be regulated not only by gene amplification, but also by other molecular mechanisms. (Cancer Sci 2009; 100: 896–902)
Patient perceptions of the burden of coeliac disease and its treatment in the UK
Authors: WHITAKER J. K. H. , WEST J. , HOLMES G. K. T. , LOGAN R. F. A.
Published: February 2009

Background  Coeliac disease affects about 1% of the population, with the majority being undetected. As a consequence, there have been calls for the introduction of screening. Before screening is given serious consideration, it is important to assess how acceptable early diagnoses and treatment would be.

Aim   To assess patients’ views as to the diagnosis and treatment of disease.

Methods  Coeliac disease patients who had taken a gluten‐free diet for at least 12 months (mean 60 months) were mailed a questionnaire. Coeliac patients presenting with typical classical symptoms were compared with those diagnosed without such symptoms.

Results  Overall, 83% (147/177) of coeliac patients returned the questionnaires. Two‐thirds (68%, 101/147) reported that their dietary restrictions reduced their enjoyment of food; 46% (68/147) believed their food cost them more and estimated this to be an extra £10 (€16) per week. Of those reporting greater cost, 31 (21%) said this was a problem for them. Half (54%, 80/147) reported doing things they enjoyed less often because of their diet, with the most common activity sacrificed being dining out (n = 65). In spite of these findings, 81% (119/147) reported being pleased that they were diagnosed, with 66% (59/89) of cases with classical symptoms wishing they had been diagnosed earlier compared with 45% (23/51) of those without such symptoms (χ2 = 6.0, P < .05). In contrast, 27% (14/51) of coeliacs diagnosed without classical symptoms regretted being diagnosed with their condition compared with 10% (9/89) of those with classical symptoms (χ2 = 7.1, P < .01).

Conclusions  Even after several years of a gluten‐free diet, many patients with coeliac disease regard it as a substantial burden, with a quarter of screen detected patients reporting regret at being diagnosed. Our findings question how acceptable screening for coeliac disease would be in people with minimal or no symptoms.
Relationship between omalizumab pharmacokinetics, IgE pharmacodynamics and symptoms in patients with severe persistent allergic (IgE‐mediated) asthma
Authors: Lowe Philip J. , Tannenbaum Stacey , Gautier Aurelie , Jimenez Pablo
Published: February 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• It had been hypothesized that there must be a relationship between free IgE concentrations and the signs and symptoms of asthma – after all, this is what drove the development of omalizumab.

• However, although many statistical analyses of free IgE and spirometry data for patients equilibrated on omalizumab had shown a difference between placebo and treatment, no consistent time‐ and IgE‐dependent relationship had been shown due to the narrow range of free IgE being studied and the sparse nature of the sampling and clinical measurements in Phase III trials.

WHAT THIS STUDY ADDS

• The above problem was solved using a pharmacokinetic–pharmacodynamic (PK–PD) model to estimate free IgE concentrations for all time points throughout and after treatment with omalizumab, together with patient daily diary data.

• This allowed for the first time the direct correlation between free IgE and signs and symptoms of asthma to be observed.

• Doses and regimens for omalizumab could then be derived, through PK–PD model simulation, for suppressing free IgE to a point correlated with an improvement in clinical symptoms.

AIMS

Omalizumab, a subcutaneously administered anti‐IgE antibody, is effective for moderate‐to‐severe persistent allergic asthma. The aims were to (i) describe the population pharmacodynamics of free IgE with a mechanism‐based, nonlinear, omalizumab–IgE binding model; (ii) deduce a target‐free IgE suppression level by correlation with clinical outcomes; and (iii) check the adequacy of current approved dosing tables and explore potential doses and regimens beyond.

METHODS

Concentration data (omalizumab, free and total IgE) were obtained from 1781 patients aged 12–79 years, in four sparsely sampled randomized, placebo‐controlled studies and 152 subjects in a richly sampled single‐dose study. NONMEM predictive performance across the range of bodyweights (39–150 kg) and baseline IgE (19–1055 IU ml−1) was checked by simulation. Predicted free IgE levels were correlated with time‐averaged patient diary clinical outcomes.

RESULTS

The model accurately predicted observed omalizumab, free and total IgE concentrations. Free IgE concentrations correlated well with clinical signs and symptoms, allowing a target concentration of 14 ng ml−1, at the midpoint of 4‐week clinical observation periods, to be set for determining the dose and regimen for omalizumab.

CONCLUSIONS

The omalizumab–IgE binding model is predictive for free IgE and demonstrates a nonlinear time‐dependent relationship between free IgE suppression and clinical outcomes in asthma. Although currently approved dosing tables are close to optimal, it should be possible to treat patients with higher levels of baseline IgE if higher doses can be administered.
Using fractional exhaled nitric oxide to guide asthma therapy: design and methodological issues for ASthma TReatment ALgorithm studies
Authors: Gibson P. G.
Published: February 2009

Background
Current asthma guidelines recommend treatment based on the assessment of asthma control using symptoms and lung function. Noninvasive markers are an attractive way to modify therapy since they offer improvedselection of active treatment(s) based on individual response, and improvedtitration of treatment using markers that are better related to treatment outcomes.

Aims: To review the methodological and design features of noninvasive marker studies in asthma.

Methods
Systematic assessment of published randomized trials of asthma therapy guided by fraction of exhaled nitric oxide(FENO).

Results
FENO has appeal as a marker to adjust asthma therapy since it is readily measured, gives reproducible results, and is responsive to changes in inhaled corticosteroid doses. However, the five randomised trials of FENO guided therapy have had mixed results. This may be because there are specific design and methodological issues that need to be addressed in the conduct of ASthma TReatment ALgorithm(ASTRAL) studies. There needs to be a clear dose response relationship for the active drugs used and the outcomes measured. The algorithm decision points should be based on outcomes in the population of interest rather than the range of values in healthy people, and the algorithm used needs to provide a sufficiently different result to clinical decision making in order for there to be any discernible benefit. A new metric is required to assess the algorithm performance, and the discordance:concordance(DC) ratio can assist with this.

Conclusion
Incorporating these design features into future FENO studies should improve the study performance and aid in obtaining a better estimate of the value of FENO guided asthma therapy.
Ecological factors drive differentiation in wolves from British Columbia
Authors: Muñoz‐Fuentes Violeta , Darimont Chris T. , Wayne Robert K. , Paquet Paul C. , Leonard Jennifer A.
Published: February 2009

Aim Limited population structure is predicted for vagile, generalist species, such as the grey wolf (Canis lupusL.). Our aims were to study how genetic variability of grey wolves was distributed in an area comprising different habitats that lay within the potential dispersal range of an individual and to make inferences about the impact of ecology on population structure.

Location British Columbia, Canada – which is characterized by a continuum of biogeoclimatic zones across which grey wolves are distributed – and adjacent areas in both Canada and Alaska, United States.

Methods We obtained mitochondrial DNA control region sequences from grey wolves from across the province and integrated our genetic results with data on phenotype, behaviour and ecology (distance, habitat and prey composition). We also compared the genetic diversity and differentiation of British Columbia grey wolves with those of other North American wolf populations.

Results We found strong genetic differentiation between adjacent populations of grey wolves from coastal and inland British Columbia. We show that the most likely factor explaining this differentiation is habitat discontinuity between the coastal and interior regions of British Columbia, as opposed to geographic distance or physical barriers to dispersal. We hypothesize that dispersing grey wolves select habitats similar to the one in which they were reared, and that this differentiation is maintained largely through behavioural mechanisms.

Main conclusions The identification of strong genetic structure on a scale within the dispersing capabilities of an individual suggests that ecological factors are driving wolf differentiation in British Columbia. Coastal wolves are highly distinct and representative of a unique ecosystem, whereas inland British Columbia grey wolves are more similar to adjacent populations of wolves located in Alaska, Alberta and Northwest Territories. Given their unique ecological, morphological, behavioural and genetic characteristics, grey wolves of coastal British Columbia should be considered an Evolutionary Significant Unit (ESU) and, consequently, warrant special conservation status. If ecology can drive differentiation in a highly mobile generalist such as the grey wolf, ecology probably drives differentiation in many other species as well.
The correlation of hepatocyte nuclear factor 4 alpha and 3 beta with hepatitis B virus replication in the liver of chronic hepatitis B patients
Authors: Long Y. , Chen E. , Liu C. , Huang F. , Zhou T. , He F. , Liu L. , Liu F. , Tang H.
Published: February 2009

Summary.  Hepatocyte nuclear factors 4 alpha (HNF4α) and 3 beta (HNF3β) are members of a group of liver‐enriched transcription factors (LETFs) that play important roles in regulating the replication of hepatitis B virus (HBV). Using cell culture and animal models, we showed that HNF4α supports HBV replication in nonhepatic cells and HNF3β inhibits HBV replication. However, the expression of HNF4α and HNF3β in the liver tissue of chronic HBV‐infected patients and the relationship between the levels of HNF4α and HNF3β and HBV replication are unclear. In this study, liver biopsy specimens from 86 chronic HBV‐infected patients were collected. The expression levels of HNF4α, HNF3β, hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) were detected by an immunohistochemical technique and the level of HBV DNA was checked by in situ hybridization with serial sections from liver biopsy tissue samples. We show here that samples with higher levels of HNF4α expression also have higher levels of HBsAg, HBcAg and HBV DNA. In contrast, in samples with higher levels of HNF3β expression, levels of HBsAg, HBcAg and HBV DNA were lower. There was a positive correlation between HNF4α expression and HBV replication, and a negative correlation between HNF3β expression and HBV replication, in the liver of chronic HBV‐infected patients. This suggests that HNF4α and HNF3β likely participate in HBV replication in patients with HBV infection, or that HBV replication may somehow influence the expression of HNF4α and HNF3β in the liver.
The wild goats Capra aegagrus Erxleben, 1777 of the Mediterranean Sea and the Eastern Atlantic Ocean islands
Authors: MASSETI MARCO
Published: February 2009

Populations of wild goats that can be referred to as phenotypes of the pasang, or Bezoar goat, or wild goat Capra aegagrus Erxleben, 1777, still occur on several of the Mediterranean and Eastern Atlantic islands. Other populations became extinct not many decades ago.

Fossil evidence for the natural spread of the wild goat to any of these islands has not been found. Originating in the Near East, the region of its natural range and its earliest domestication, the species was introduced by humans onto the Mediterranean islands starting as early as the Pre‐Pottery Neolithic.

The islands of the Eastern Atlantic were colonized artificially by animals of ‘pre‐Hispanic’ origin. The principal phenotypes expressed by all these populations of goats can be matched with the characteristics of both C. a. aegagrus Erxleben, 1777 (aegagrus phenotype) and C. a. dorcas Reichenow, 1888 (dorcas phenotype).

Most of these animals currently survive on the islands without being fed by humans, and should be protected.
Effects of α1‐acid Glycoprotein Fucosylation on its Ca2+ Mobilizing Capacity in Neutrophils
Authors: Levander L. , Gunnarsson P. , Grenegård M. , Rydén I. , Påhlsson P.
Published: February 2009

We recently showed that the acute‐phase protein α1‐acid glycoprotein (AGP) induces rises in cytosolic calcium concentration, [Ca2+]i, in neutrophils through sialic acid dependent interactions with the neutrophil receptors siglec‐5 and/or siglec‐14. Whereas both siglec‐5 and siglec‐14 have a relatively broad specificity for sialylated oligosaccharide structures, including both structures with terminal α2–3 or α2–6 linked sialic acid, there is a markedly reduced affinity to the fucosylated epitope sialyl Lewis x (SLex). Increased fucosylation, leading to increased expression of SLex on AGP is commonly associated with inflammatory conditions. In the present study, we investigated whether an increased SLex expression would affect the Ca2+‐mobilizing effect of AGP. AGP with elevated fucose content isolated from patients with untreated chronic joint inflammation showed a decreased [Ca2+]i modulatory effect on neutrophils compared to normally fucosylated AGP. Furthermore a hyperfucosylated AGP form produced by in vitro fucosylation, that consequently had an elevated expression of SLex, could not elicit a [Ca2+]i increase in neutrophils. The role of the carbohydrate portion of AGP in modulating neutrophil responses was further strengthened by showing that synthetic glycoconjugates carrying oligosaccharides with terminal α2–3 or α2–6 linked sialic acid were able to mimic the Ca2+‐mobilizing effect of AGP whereas a synthetic glycoconjugate carrying SLex was not. Based on these data, we conclude that increased fucosylation can alter the ability of AGP to induce neutrophil signalling and further supports an important role of the oligosaccharide chains of AGP in the modulation of leukocyte functions during an inflammatory process.
Herpes Simplex Virus Infection Downmodulates NKG2D Ligand Expression
Authors: Schepis D. , D’Amato M. , Studahl M. , Bergström T. , Kärre K. , Berg L.
Published: February 2009

Herpes simplex virus (HSV) type 1 infection may cause orofacial infections in humans. The virus resides in a latent form in neural ganglia and occasionally reactivates and infects epithelial cells. Natural killer (NK) cells have been implicated in immune control of herpes virus infections, possibly by downmodulating major histocompatibility complex (MHC) class I and by other, as yet unidentified, mechanisms. Upon HSV‐1 infection of cell lines, surface levels of NKG2D ligands MHC class I related proteins (MIC) A and UL16 binding protein 2 were downmodulated due to late viral gene product(s). As also MHC class I levels were reduced by HSV‐1, NK cell recognition of HeLa cells was not affected by infection. Total cellular MICA contents remained unchanged, suggesting masking, internalization or intracellular retention of MICA as possible mechanisms of viral downregualtion of MICA surface levels. Furthermore, NK cells from patients with active HSV‐1 infection had a tendency towards increased expression level of the activating receptor NKG2D. These data support a role for NKG2D–MICA interactions in immune responses to HSV‐1 reactivation.
Identification of the Arabidopsis dry2/sqe1‐5 mutant reveals a central role for sterols in drought tolerance and regulation of reactive oxygen species
Authors: Posé David , Castanedo Itziar , Borsani Omar , Nieto Benjamín , Rosado Abel , Taconnat Ludivine , Ferrer Albert , Dolan Liam , Valpuesta Victoriano , Botella Miguel A.
Published: February 2009

Squalene epoxidase enzymes catalyse the conversion of squalene into 2,3‐oxidosqualene, the precursor of cyclic triterpenoids. Here we report that the Arabidopsis drought hypersensitive/squalene epoxidase 1‐5 (dry2/sqe1‐5) mutant, identified by its extreme hypersensitivity to drought stress, has altered stomatal responses and root defects because of a point mutation in the SQUALENE EPOXIDASE 1 (SQE1) gene. GC‐MS analysis indicated that the dry2/sqe1‐5 mutant has altered sterol composition in roots but wild‐type sterol composition in shoots, indicating an essential role for SQE1 in root sterol biosynthesis. Importantly, the stomatal and root defects of the dry2/sqe1‐5 mutant are associated with altered production of reactive oxygen species. As RHD2 NADPH oxidase is de‐localized in dry2/sqe1‐5 root hairs, we propose that sterols play an essential role in the localization of NADPH oxidases required for regulation of reactive oxygen species, stomatal responses and drought tolerance.
Macroscopic Anatomy of the Great Vessels and Structures Associated with the Heart of the Ringed Seal (Pusa hispida)
Authors: Smodlaka H. , Henry R. W. , Reed R. B.
Published: February 2009

The ringed seal [Pusa (Phoca) hispida], as well as other seals, exhibits unique anatomical properties when compared to its terrestrial counterparts. In the ringed seal, the most conspicuous marine adaptation is the aortic bulb. This large dilatation of the ascending aorta is comparable to that found in other seal species and marine mammals. The branches of the ascending aorta (brachiocephalic trunk, left common carotid artery and left subclavian artery) are similar to those of higher primates and man. The peculiarities of the venous system are: three pulmonary veins, a pericardial venous plexus, a caval sphincter, a hepatic sinus with paired caudal vena cavae and a large extradural venous plexus. Generally, three common pulmonary veins (right, left and caudal) empty into the left atrium. The pericardial venous plexus lies deep to the mediastinal pericardial pleura (pleura pericardica) on the auricular (ventral) surface of the heart. The caval sphincter surrounds the caudal vena cava as it passes through the diaphragm. Caudal to the diaphragm, the vena cava is dilated (the hepatic sinus), and near the cranial extremity of the kidneys, it becomes biphid. The azygos vein is formed from the union of the right and left azygos veins at the level of the 5th thoracic vertebra. Cardiovascular physiological studies show some of these anatomical variations, especially of the venous system and the ascending aorta, to be modifications for diving. This investigation documents the large blood vessels associated with the heart and related structures in the ringed seal.
Delayed Lung Maturation of Foetus of Diabetic Mother Rats Develop with a Diminish, but Without Changes in the Proportion of Type I and II Pneumocytes, and Decreased Expression of Protein D‐Associated Surfactant Factor
Authors: Treviño‐Alanís M. , Ventura‐Juárez J. , Hernández‐Piñero J. , Nevárez‐Garza A. , Quintanar‐Stephano A. , González‐Piña A.
Published: February 2009

Newborn children of diabetic mothers have an increased morbidity and mortality because of respiratory distress syndrome. We study lung histogenesis during intrauterine development of offspring of diabetic Sprague‐Dawley rats at 18, 19 and 21 days of gestation (DG). Pregnant rats were grouped into diabetic (streptozotocin‐induced), citrate, and control groups; five female and five male offspring were selected randomly from each group at 18, 19 and 21 DG, and a biopsy of the lung was taken and processed in paraffin for histological examination. The biopsy for the transmission electron microscopy (TEM) analysis was taken at 21 days. A delay in alveolization of the offspring at 18, 19 and 21 days of the diabetic group was observed, which was confirmed at TEM level, and also less quantity of protein D associated to surfactant in diabetic group was detected (P < 0.001). The foetuses of the diabetic group presented a delay in lung histogenesis and in differentiation of the type II pneumocytes cells, but conserved the proportion with a decrease in 50% of pneumocytes, accompanied by a diminish of protein D associated to surfactant factor.
Effectiveness of GF‐120NF Fruit Fly Bait as a suppression tool for Bactrocera latifrons (Diptera: Tephritidae)
Authors: McQuate G. T.
Published: February 2009

Bactrocera latifrons (Hendel) is a tephritid fruit fly of primarily Asian distribution that has invaded Hawaii and, more recently, the continent of Africa (Tanzania and Kenya). It primarily infests solanaceous fruits, so has the potential to impact production of crops such as peppers (Capsicum annuum L. and Capsicum frutescens L.), eggplant (Solanum melongena L.), African eggplant (Solanum aethiopicum L.) and tomatoes (Solanum lycopersicum L.). Because little work has been done to develop suppression techniques for this fruit fly species, field cage tests of the effectiveness of a commercially available bait spray, GF‐120NF Fruit Fly Bait, against wild B. latifrons were conducted. Sexually mature B. latifrons adults (75 male and 75 female) were introduced to both a control cage and a treatment cage, each of which held six fruiting Anaheim chili pepper (C. annuum L.) plants. Fruits were harvested, and assessed for infestation, both before and after the application of the bait spray in the treatment cage. There was no difference in infestation rate between control and treatment cages before the application of the bait spray, whereas there was a significantly lower infestation rate in treatment cages following the application of the bait spray. Post‐spray infestation rate in the treatment cages (in two separate, replicated bioassays) was always zero and no live flies were detected in the treatment cages at the end of the trials. The results of this study provide evidence that GF‐120NF Fruit Fly Bait should be effective in suppressing B. latifrons populations in the field.
Learning from the past, looking to the future: Exploring our place with Indigenous Australians
Authors: Nelson Alison
Published: February 2009

This paper aims to explore ways in which we as occupational therapists in Australia can participate in enabling a different and better future for all Australians. In doing so, it is necessary to explore our history and our cultures, both individually and collectively as a profession, and to understand the ways in which these shape who we are and what we do. As occupational therapists, we have valuable knowledge and skills that have the potential to contribute in a positive way to the health and educational outcomes of Indigenous Australians. As a profession operating in Australia, we also have a responsibility to reach this potential. This paper aims to present some of these contributions and to provide examples of practical and culturally safe ways in which we can take action.
The modulation of visual orienting reflexes across the lifespan
Authors: Iarocci Grace , Enns James T. , Randolph Beth , Burack Jacob A.
Published: February 2009

The development of reflexive and voluntary shifts of visual attention, as well as relations between the two forms of shifting, were examined in three groups of children (5, 7, and 9 years old), one group of young adults (24 years old), and two groups of senior adults (young seniors with an average age of 69 years, and old seniors with an average age of 81 years). The task entailed response to the detection of a target (black dot) in one of four possible locations in the visual field. Relations between reflexive and voluntary shifts of attention were gauged by the degree to which flash and arrow facilitation and inhibition were observed in response to the presentation of both arrow and flash cues together in one trial. All age groups oriented reflexively in response to a flash cue and utilized the arrow cue to orient attention strategically. When flash and arrow cues were presented in quick succession and thereby competed for attention, the youngest children and oldest seniors were least efficient and flexible in their approach to the orienting task as they had difficulty modulating visual reflexes.
Weighting of vowel cues explains patterns of word–object associative learning
Authors: Curtin Suzanne , Fennell Christopher , Escudero Paola
Published: February 2009

Previous research has demonstrated that infants under 17 months have difficulty learning novel words in the laboratory when the words differ by only one consonant sound, irrespective of the magnitude of that difference. The current study explored whether 15‐month‐old infants can learn novel words that differ in only one vowel sound. The rich acoustic/phonetic properties of vowels allow for a detailed analysis of the contribution of acoustic/phonetic cues to infants’ performance with similar‐sounding words. Infants succeeded with the vowel pair /i/–/I/, but failed with vowel pairs /i/–/u/ and /I/–/u/. These results suggest that infants initially use the most salient acoustic cues for vowels and that this staged use of acoustic cues both predicts and explains why infants can learn some words that differ in only a single vowel.
Long Work Hours: Volunteers and Conscripts
Authors: Drago Robert , Wooden Mark , Black David
Published: February 2009

Using panel survey data from Australia, we divide long hours workers (persons reporting usually working 50 or more hours per week) into groups of ‘volunteers’, who prefer long hours, and ‘conscripts’, who do not. We study both the static and dynamic prevalence of the phenomenon. Norms surrounding ideal workers and consumerism play major roles in explaining conscript status, with bargaining power less important. The self‐employed often appear as volunteers or conscripts, while gender, rather than motherhood, is a strong predictor of shorter work hours. Both the demand and supply sides of the labour market play a role in explaining the prevalence of long hours conscripts.
Transformation Direction Influences Shape-Similarity Judgments
Authors: Hahn Ulrike , Close James , Graf Markus
Published: February 2009

Three experiments provide evidence that the perceived similarity between two images is systematically affected by the inherent direction of a transformation that links the two. Participants were shown short animations morphing one object into another from the same basic category. They were then asked to make directional similarity judgments (“How similar is object A to object B?”) for two stationary images drawn from the morph continuum. Across three experiments, similarity ratings for identical comparisons were higher when the reference object, B, had appeared before the comparison object, A, in the preceding morph sequence. This response to dynamic transformational sequences is in accordance with the view that similarity depends on the ease of transformation between object representations and that transformations between objects in categorization and object recognition are psychologically real.
Treatment of cutaneous leishmaniasis with intralesional sodium stibogluconate
Authors: Solomon M , Baum S , Barzilai A , Pavlotsky F , Trau H , Schwartz E
Published: February 2009

Background  Cutaneous leishmaniasis is endemic in Israel. Leishmania major is the most prevalent species that cause cutaneous leishmaniasis. Current treatment options are limited and there are few investigations in search of alternative ones.

Objective  This study aims to assess our experience with intralesional sodium stibogluconate (SSG) in the treatment of cutaneous leishmaniasis.

Methods  A retrospective evaluation for all adult cases of cutaneous leishmaniasis treated by intralesional and intravenous SSG (Pentostam®, GlaxoSmithKline) between 2004 and 2006 was performed, for cases referred to a tertiary care university‐affiliated medical centre in Israel. Intralesional SSG was injected at 0.5 mL per lesion (50 mg). Treatment was repeated every 2–3 weeks for a total of 12 weeks. Intravenous SSG was administered at a dose of 20 mg/kg for 10–20 days.

Results  Thirty‐three cases of cutaneous leishmaniasis were treated with intralesional SSG during the study period. The patients consist of 26 males and 7 females, mostly Israeli military personnel, and there were a total of 93 lesions. Within 3 months from treatment onset, 91% (30/33) had completed healing of the cutaneous lesions after an average of 3 treatments (range 1–6). Side‐effects were mild and were mostly pain during injection, with two patients developing mild local site reaction after the injection.

Conclusions  Intralesional SSG treatment is safe, effective and well tolerated with minimal side‐effects.
Generalized‐onset seizures with secondary focal evolution
Authors: Williamson Randy , Hanif Samrina , Mathews Gregory C. , Lagrange Andre H. , Abou‐Khalil Bassel
Published: February 2009

The international seizure classification recognizes that partial‐onset seizures can become secondarily generalized, but generalized‐onset seizures are expected to remain generalized. We report six patients who had recorded seizures with generalized onset, but subsequent evolution into a focal discharge. The clinical seizure onset was generalized absence or myoclonic, and the most common subsequent clinical pattern was prolonged behavioral arrest with mild automatisms, and then postictal confusion. The ictal discharge started with generalized spike‐and‐wave activity and then acquired a focal predominance. Interictal epileptiform activity was generalized. There were no focal magnetic resonance imaging abnormalities. Four patients were misdiagnosed with complex partial seizures. All patients were initially refractory, but three became seizure‐free and three improved after treatment with antiepileptic medications appropriate for absence or myoclonic seizures. Generalized‐onset seizures that acquire focal features are easily misdiagnosed as complex partial. These seizures have a more favorable response to medications effective against generalized absence and myoclonic seizures.
Transsexualism: Some Theological and Ethical Perspectives
Authors: Childs James M.
Published: February 2009

Abstract:  The debates in church and theological circles regarding sexuality have been dominated by the subject of homosexuality. There has been far less theological discussion and ethical reflection regarding transgendered people and transsexualism in particular. This article introduces readers to some basic facts about transsexualism and to a selection of theological and ethical responses to this phenomenon with particular attention to how the notion of “disordered sexuality” is a factor in both the debate over the ethical status of transsexualism and homosexual unions.
Gay, Lesbian, and Queer Theologies: Origins, Contributions, and Challenges
Authors: Lowe Mary Elise
Published: February 2009

Abstract:  Theologians and biblical scholars have been writing about Christianity and homosexuality for over three decades, but lesbian/gay and queer theologies are still unfamiliar. Since questions about lesbian, gay, and queer Christians are confronting many denominations, it is important to study these proposals. This essay argues that lesbian/gay theologies trace their histories to theologies of liberation, while queer theology is indebted to postmodern and queer theories. Recent Christological and anthropological proposals are presented, and the essay concludes by exploring the distinct political implications of these theological proposals.
The Problem with Sex According to Buddhism
Authors: Numrich Paul David
Published: February 2009

Abstract:  This essay offers a primer for readers unfamiliar with Buddhist sexual ethics. Sex is a problem for Buddhism because it epitomizes the human predicament and the difficulty of its resolution. The essay begins with religious views of the human predicament and its resolution, and how these views shape religious ethical systems. Next follows a brief section on the Buddha and his teachings about human existence and ethical living, focusing particularly on the ultimate goal of liberation from the unsatisfactoriness of a life driven by desire. Given Buddhism's historic emphasis on a renunciatory ideal modeled by a monastic community, a substantial portion of the essay examines the disciplinary rules and sexual behaviors of Buddhist monks and nuns. Sexual ethics for lay Buddhists and non‐conventional sexual categories round out the essay.
‘Born Sinners’ Striving for Perfection: Criteria for the Construction of a Contemporary Lutheran Theology of Original Sin
Authors: Grantén Eva‐Lotta
Published: February 2009

Abstract:  This essay aims to identify some criteria Lutheran theology must meet when working towards a new construction of human imperfection. It must be contextual and open towards a dialogue with disciplines seeking knowledge of human nature. Theology must take evil and suffering seriously, while still recognizing humanity's ability to make life better. It must affirm that not only human nature, but also human culture needs transformation.