bluuebunny/crossref_metadata_2025 huggingface dataset:
A Single Phenylalanine Residue in the Main Intracellular Loop of α1 γ-Aminobutyric Acid Type A and Glycine Receptors Influences Their Sensitivity to Propofol
Authors: Moraga-Cid Gustavo , Yevenes Gonzalo E. , Schmalzing Günther , Peoples Robert W. , Aguayo Luis G.
Published: June 2011

Background

The intravenous anesthetic propofol acts as a positive allosteric modulator of glycine (GlyRs) and γ-aminobutyric acid type A (GABAARs) receptors. Although the role of transmembrane residues is recognized, little is known about the involvement of other regions in the modulatory effects of propofol. Therefore, the influence of the large intracellular loop in propofol sensitivity of both receptors was explored.

Methods

The large intracellular loop of α1 GlyRs and α1β2 GABAARs was screened using alanine replacement. Sensitivity to propofol was studied using patch-clamp recording in HEK293 cells transiently transfected with wild type or mutant receptors.

Results

Alanine mutation of a conserved phenylalanine residue within the α1 large intracellular loop significantly reduced propofol enhancement in both GlyRs (360 ± 30 vs. 75 ± 10%, mean ± SEM) and GABAARs (361 ± 49% vs. 80 ± 23%). Remarkably, propofol-hyposensitive mutant receptors retained their sensitivity to other allosteric modulators such as alcohols, etomidate, trichloroethanol, and isoflurane. At the single-channel level, the ability of propofol to increase open probability was significantly reduced in both α1 GlyR (189 ± 36 vs. 22 ± 13%) and α1β2 GABAAR (279 ± 29 vs. 29 ± 11%) mutant receptors.

Conclusion

In this study, it is demonstrated that the large intracellular loop of both GlyR and GABAAR has a conserved single phenylalanine residue (F380 and F385, respectively) that influences its sensitivity to propofol. Results suggest a new role of the large intracellular loop in the allosteric modulation of two members of the Cys-loop superfamily. Thus, these data provide new insights into the molecular framework behind the modulation of inhibitory ion channels by propofol.
Geoffrey Herbert Beale MBE. 11 June 1913 — 16 October 2009
Authors: Preer John R. , Tait Andrew
Published: June 2011

Professor Geoffrey Beale was one of the UK's leading protozoan geneticists with an international reputation. His enthusiasm for the use of genetic analysis to address fundamental questions in the biology of both free-living and parasitic protozoa was based on the influence of a series of leading geneticists whom he worked with in the early part of his career in the John Innes Horticultural Institute and Cold Spring Harbor. His research started with plants and
Escherichia coli
. Later he moved his research to
Paramecium
, under the mentorship of Tracy Sonneborn (ForMemRS 1964). His work on the surface antigens of
Paramecium
was published in the early 1950s, at a time when there was much debate about the role of nuclear genes and elements in the cytoplasm in determining phenotype. This was a period when the nature of the genetic material was uncertain and many scientists believed that genes were proteins. Two of his papers published at that time provided a synthesis that explained how environmental signals and the cytoplasmic state determined whether a gene was expressed (1, 2)*. These findings provided one of the first cases of the regulation of gene expression at a conceptual level and provided a bridge between those promoting cytoplasmic inheritance and those fixed on nuclear genes as the sole determinants of phenotype. In the period from 1966, he also initiated research on extranuclear (mitochondrial) genetics and on the genetics of rodent and human malaria parasites, leading to several fundamental and important findings. This was a very productive period and included the establishment of links with a malaria research group in Thailand directed by Dr Sodsri Thaithong, leading to studies on the genetic basis of malaria drug resistance and studies on strain variation in
Plasmodium falciparum
. In the latter part of his career and into retirement, he took a more advisory role in his research group but his enthusiasm and interest stimulated those around him enormously.
Return to Beringia: parasites reveal cryptic biogeographic history of North American pikas
Authors: Galbreath Kurt E. , Hoberg Eric P.
Published: June 2011

Traditional concepts of the Bering Land Bridge as a zone of predominantly eastward expansion from Eurasia and a staging area for subsequent colonization of lower latitudes in North America led to early inferences regarding biogeographic histories of North American faunas, many of which remain untested. Here we apply a host–parasite comparative phylogeographical (HPCP) approach to evaluate one such history, by testing competing biogeographic hypotheses for five lineages of host-specific parasites shared by the collared pika (Ochotona collaris) and American pika (Ochotona princeps) of North America. We determine whether the southern host species (O. princeps) was descended from a northern ancestor or vice versa. Three parasite phylogenies revealed patterns consistent with the hypothesis of a southern origin, which is corroborated by four additional parasite lineages restricted toO. princeps. This finding reverses the traditional narrative for the origins of North American pikas and highlights the role of dispersal from temperate North America into Beringia in structuring northern diversity considerably prior to the Holocene. By evaluating multiple parasite lineages simultaneously, the study demonstrates the power of HPCP for resolving complex biogeographic histories that are not revealed by characteristics of the host alone.
Male cleaner wrasses adjust punishment of female partners according to the stakes
Authors: Raihani Nichola J. , Pinto Ana I. , Grutter Alexandra S. , Wismer Sharon , Bshary Redouan
Published: June 2011

Punishment is an important deterrent against cheating in cooperative interactions. In humans, the severity of cheating affects the strength of punishment which, in turn, affects the punished individual's future behaviour. Here, we show such flexible adjustments for the first time in a non-human species, the cleaner wrasse (
Labroides dimidiatus
), where males are known to punish female partners. We exposed pairs of cleaners to a model client offering two types of food, preferred ‘prawn’ items and less-preferred ‘flake’ items. Analogous to interactions with real clients, eating a preferred prawn item (‘cheating’) led to model client removal. We varied the extent to which female cheating caused pay-off reduction to the male and measured the corresponding severity of male punishment. Males punished females more severely when females cheated during interactions with high value, rather than low value, model clients; and when females were similar in size to the male. This pattern may arise because, in this protogynous hermaphrodite, cheating by similar-sized females may reduce size differences to the extent that females change sex and become reproductive competitors. In response to more severe punishment from males, females behaved more cooperatively. Our results show that punishment can be adjusted to circumstances and that such subtleties can have an important bearing on the outcome of cooperative interactions.
Methylobacterium

cerastii sp. nov., isolated from the leaf surface of Cerastium holosteoides
Authors: Wellner S. , Lodders N. , Kämpfer P.
Published: June 2011

Two Gram-stain-negative, non-endospore-forming, rod-like strains, designated C15T and C44, were isolated from the phyllosphere of Cerastium holosteoides and were studied in detail in order to assess their taxonomic position. 16S rRNA gene sequence analysis allocated both isolates clearly to the genus

Methylobacterium

. Both strains showed the highest 16S rRNA gene sequence similarity to

Methylobacterium marchantiae

JT1T (97.5 %) and

Methylobacterium jeotgali

S2R03-9T (97.4 %). The fatty acid profiles contained major amounts of C16 : 0, C18 : 1ω7c and C16 : 1ω7c/iso-C15 : 0 2-OH (summed feature 3), which supported the grouping of the isolates in the genus

Methylobacterium

. Physiological/biochemical characterization and DNA–DNA hybridizations with the type strains of the most closely related species allowed a clear phenotypic and genotypic differentiation of the strains. For this reason, we propose for strain C15T ( = DSM 23679T  = CCUG 60040T  = CCM 7788T) a novel species with the name
Methylobacterium

cerastii sp. nov. Strain C44 ( = DSM 23675  = CCM 7789) is an additional strain of M. cerastii.
Proline Accumulation Is Inhibitory to Arabidopsis Seedlings during Heat Stress
Authors: Lv Wei-Tao , Lin Bin , Zhang Min , Hua Xue-Jun
Published: June 2011

The effect of proline (Pro) accumulation on heat sensitivity was investigated using transgenic Arabidopsis (Arabidopsis thaliana) plants ectopically expressing the Ɗ(1)-pyrroline-5-carboxylate synthetase 1 gene (AtP5CS1) under the control of a heat shock protein 17.6II gene promoter. During heat stress, the heat-inducible expression of the AtP5CS1 transgene was capable of enhancing Pro biosynthesis. Twelve-day-old seedlings were first treated with heat at 37°C for 24 h to induce Pro and then were stressed at 50°C for 4 h. After recovery at 22°C for 96 h, the growth of Pro-overproducing plants was significantly more inhibited than that of control plants that do not accumulate Pro, manifested by lower survival rate, higher ion leakage, higher reactive oxygen species (ROS) and malondialdehyde levels, and increased activity of the Pro/P5C cycle. The activities of antioxidant enzymes superoxide dismutase, guaiacol peroxidase, and catalase, but not those of glutathione reductase and ascorbate peroxidase, increased in all lines after heat treatment, but the increase was more significant in Pro-overproducing seedlings. Staining with MitoSox-Red, reported for being able to specifically detect superoxide formed in mitochondria, showed that Pro accumulation during heat stress resulted in elevated levels of ROS in mitochondria. Interestingly, exogenous abscisic acid (ABA) and ethylene were found to partially rescue the heat-sensitive phenotype of Pro-overproducing seedlings. Measurement of ethylene and ABA levels further confirmed that these two hormones are negatively affected in Pro-overproducing seedlings during heat stress. Our results indicated that Pro accumulation under heat stress decreases the thermotolerance, probably by increased ROS production via the Pro/P5C cycle and inhibition of ABA and ethylene biosynthesis.
TheArabidopsisNAC Transcription Factor VNI2 Integrates Abscisic Acid Signals into Leaf Senescence via theCOR/RDGenes
Authors: Yang So-Dam , Seo Pil Joon , Yoon Hye-Kyung , Park Chung-Mo
Published: June 2011

Leaf aging is a highly regulated developmental process, which is also influenced profoundly by diverse environmental conditions. Accumulating evidence in recent years supports that plant responsiveness to abiotic stress is intimately related with leaf longevity. However, molecular mechanisms underlying the signaling crosstalks and regulatory schemes are yet unknown. In this work, we demonstrate that an abscisic acid (ABA)–responsive NAC transcription factor VND-INTERACTING2 (VNI2) integrates ABA-mediated abiotic stress signals into leaf aging by regulating a subset of COLD-REGULATED (COR) and RESPONSIVE TO DEHYDRATION (RD) genes. The VNI2 gene was induced by high salinity in an ABA-dependent manner. In addition, spatial and temporal expression patterns of the VNI2 gene are correlated with leaf aging and senescence. Accordingly, leaf aging was delayed in transgenic plants overexpressing the VNI2 gene but significantly accelerated in a VNI2-deficient mutant. The VNI2 transcription factor regulates the COR and RD genes by binding directly to their promoters. Notably, transgenic plants overexpressing the COR or RD genes exhibited prolonged leaf longevity. These observations indicate that the VNI2 transcription factor serves as a molecular link that integrates plant responses to environmental stresses into modulation of leaf longevity.
‘Closet’ quit attempts: prevalence, correlates and association with outcome
Authors: Carpenter Matthew J. , Sterba Katherine Regan , Boatright Amy S. , West Robert
Published: June 2011

Aims  To examine the (i) prevalence, (ii) predictors and (iii) cessation outcomes of smokers who engage in undisclosed quit attempts.

Design  Online survey (n = 524), with balanced recruitment of current smokers (55%) and past‐year quitters (45%). Participants were daily smokers (current or previous) who had at least one quit attempt in the past year.

Measurements  Respondents were grouped on whether they did versus did not make advanced disclosure to others of their most recent quit attempt.

Findings  Almost half (n = 234; 45%) reported that their most recent quit attempt was undisclosed to anyone in advance. Those who planned their quit attempt in advance [odds ratio (OR) = 0.10; 95% confidence interval (CI): 0.05–0.23] and those who used behavioral treatment (OR = 0.14; 95% CI: 0.05–0.43) were less likely to make ‘closet quit attempts’, while those who rated their attempt as being serious (OR = 2.52; 95% CI: 1.16–5.46) and those who deemed social support to be unhelpful (OR = 1.91; 95% CI: 1.24–2.95) were more likely to make such attempts. Closet quit attempters were more likely to achieve 30 days of abstinence than were those who made advanced disclosure (67% versus 58%; adjusted OR 1.8; 95% CI: 1.1–2.8), but there were no differences for achieving 6 months of abstinence (52% versus 49%; adjusted OR 1.2; 95% CI: 0.7–2.0).

Conclusions  Attempting to quit smoking without telling anyone in advance is common, and does not appear to impede success. These findings do not support blanket advice to smokers to tell others about pending quit attempts.
Dosing equation for tacrolimus using genetic variants and clinical factors
Authors: Passey Chaitali , Birnbaum Angela K. , Brundage Richard C. , Oetting William S. , Israni Ajay K. , Jacobson Pamala A.
Published: June 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Patients with low tacrolimus troughs are at a higher risk of rejection while those with high troughs are at an increased risk for toxicity. Therefore, achieving the therapeutic range is important.

• CYP3A5 genotype and days post transplant have been previously shown individually to be associated with tacrolimus troughs.

WHAT THIS STUDY ADDS

• This paper presents the first dosing model for tacrolimus using a combination of genetic and clinical factors in adult kidney transplant recipients. It was developed from one of the largest tacrolimus pharmacogenetic studies conducted to date (681 subjects and 11 823 trough concentrations).

• We found that CL/F was significantly influenced by days post transplant, CYP3A5 genotype, transplantation at a steroid sparing centre, recipient age and the use of a calcium channel blocker.

• Our large sample size enabled us to define the distinct differences in tacrolimus CL/F between three CYP3A5 genotype groups (*1/*1, *1/*3 and *3/*3).

• This study is an important step towards using pharmacogenetic information in the clinical setting.

AIM To develop a dosing equation for tacrolimus, using genetic and clinical factors from a large cohort of kidney transplant recipients. Clinical factors and six genetic variants were screened for importance towards tacrolimus clearance (CL/F).

METHODS Clinical data, tacrolimus troughs and corresponding doses were collected from 681 kidney transplant recipients in a multicentre observational study in the USA and Canada for the first 6 months post transplant. The patients were genotyped for 2 724 single nucleotide polymorphisms using a customized Affymetrix SNP chip. Clinical factors and the most important SNPs (rs776746, rs12114000, rs3734354, rs4926, rs3135506 and rs2608555) were analysed for their influence on tacrolimus CL/F.

RESULTS The CYP3A5*1 genotype, days post transplant, age, transplant at a steroid sparing centre and calcium channel blocker (CCB) use significantly influenced tacrolimus CL/F. The final model describing CL/F (l h−1) was: 38.4 ×[(0.86, if days 6–10) or (0.71, if days 11–180)]×[(1.69, if CYP3A5*1/*3 genotype) or (2.00, if CYP3A5*1/*1 genotype)]× (0.70, if receiving a transplant at a steroid sparing centre) × ([age in years/50]−0.4) × (0.94, if CCB is present). The dose to achieve the desired trough is then prospectively determined using the individuals CL/F estimate.

CONCLUSIONS The CYP3A5*1 genotype and four clinical factors were important for tacrolimus CL/F. An individualized dose is easily determined from the predicted CL/F. This study is important towards individualization of dosing in the clinical setting and may increase the number of patients achieving the target concentration. This equation requires validation in an independent cohort of kidney transplant recipients.
Nurses' experiences of caring for children in pain
Authors: Ljusegren G. , Johansson I. , Gimbler Berglund I. , Enskär K.
Published: June 2011

Aim  To describe nurses' experiences when caring for children in pain.

Background  Earlier studies have shown that nurses are key actors in pain management and that there is a need to focus on the nurses' own experiences of caring for children in pain.

Method  Semi‐structured interviews were conducted with 21 nurses at one paediatric clinic. The data were analysed by means of content analysis.

Results  The interviews suggested that when a child's pain followed an expected pattern and they complied with treatment, the nurses trusted their knowledge and felt comfortable. On the other hand, in unpredictable situations the nurses felt fearful, powerless, abandoned and distrustful.

Conclusion  The nurses were comfortable in predictable situations, but if a situation was unpredictable, they felt they had lost control over it.

Implications for pain management  To reduce feelings of abandonment, work shifts should be organized so that more experienced nurses can work side by side with those who are less experienced. Pain assessment tools and guidelines for pain management should be introduced into the daily work, and systematic reflection should be used for nurses' professional development.
Assessment of clinical efficacy of CYT003‐QbG10 in patients with allergic rhinoconjunctivitis: a phase IIb study
Authors: Klimek L. , Willers J. , Hammann‐Haenni A. , Pfaar O. , Stocker H. , Mueller P. , Renner W. A. , Bachmann M. F.
Published: June 2011

Background
Allergic symptoms are generally caused by exposure to substances to which people have become sensitized. Associated with this is an ‘unbalanced’ Th1/Th2 immune response with T cell responses skewed towards the production of Th2 cytokines, IL‐4, 5, and 13 and high levels of IgE antibodies. Current immune modulating therapies require the use of allergens, carrying the risk to induce potentially severe allergic reactions.

Objective
Goal of the present study was to assess the safety and efficacy of an allergen‐free immune modulator in patients suffering from perennial allergy.

Methods
In order to be protected from immediate degradation upon injection, a toll‐like receptor 9 (TLR9) agonist was packaged into virus‐like particles. These nanoparticles loaded with TLR9 ligands (CYT003‐QbG10) were injected six times, at weekly intervals, into patients with house dust mite allergy in an attempt to ameliorate allergic symptoms by modifying the immune response towards allergens. Two different doses were compared against placebo in this double‐blind, randomized phase IIb study (n=299). Public trial registry: http://clinicaltrials.gov (NCT00800332).

Results
The treatment was safe and generally well tolerated. Rhinoconjunctivitis symptoms were significantly lower in patients treated with high dose of CYT003‐QbG10 as compared with placebo (scores 0.31 vs. 0.52, P=0.04) based on a standardized average combined symptom and medication score. Furthermore, patients in the high dose group reported a significantly better quality of life score post‐treatment than patients on placebo (scores 0.71 vs. 1.21, P=0.02). The conjunctival provocation test revealed a median 10‐fold increase in allergen tolerance in the high dose group while in the placebo group it remained unchanged.

Conclusion and Clinical Relevance
Treatment with high‐dose CYT003‐QbG10 improved disease symptoms and reduced medication use in allergic individuals thus providing first evidence for a new potential immunotherapeutic.

Cite this as: L. Klimek, J. Willers, A. Hammann‐Haenni, O. Pfaar, H. Stocker, P. Mueller, W. A. Renner and M. F. Bachmann, Clinical & Experimental Allergy, 2011 (41) 1305–1312.
Organochlorine compounds and testicular dysgenesis syndrome: human data
Authors: Cook M. B. , Trabert B. , McGlynn K. A.
Published: June 2011

Cryptorchidism, hypospadias, subfertility and testicular germ‐cell tumour have been suggested to comprise a testicular dysgenesis syndrome (TDS) based on the premise that each may derive from perturbations of embryonal programming and gonadal development during foetal life. Endocrine‐disrupting chemicals have been hypothesized to be associated with these disorders, given the importance of sex steroid hormones in urogenital development and homeostasis. Organochlorines are one such set of compounds which are defined as containing between one and ten covalently bonded chlorine atoms. These compounds are persistent pollutants with long half‐lives, accumulate in adipose tissue when ingested, bioaccumulate and biomagnify, and have complex and variable toxicological profiles. Examples of organochlorines include dichloro‐diphenyl‐trichloroethane and its metabolites, polychlorinated biphenyls, and chlordane. In this comprehensive review of human epidemiologic studies which have tested for associations between organochlorines and facets of TDS, we find evidence for associations between the exposures p,p′‐DDE, cis‐nonachlor and trans‐nonachlor with testicular germ‐cell tumour. The sum of the evidence from human epidemiological studies does not indicate any association between specific organochlorines studied and cryptorchidism, hypospadias or fertility. Many other endocrine‐disrupting chemicals, including additional organochlorines, have yet to be assessed in relation to disorders associated with TDS, yet study of such chemicals has strong scientific merit given the relevance of such hypotheses to urogenital development.
Change in aromatic components of banana during the preparation process of juice and microcapsule powder
Authors: Wang Juan , Chen Qicong , Hu Kai , Zeng Linlin , Pan Ye , Huang Huihua
Published: June 2011

Based on the importance of pleasant aroma on quality of banana products, a study was carried out on how the aromatic profile of banana is affected when fresh ripe banana is processed into puree, clear juice, microcapsulated banana powder and reconstituted juice. Solid‐phase micro‐extraction extraction and gas chromatography–mass spectrometry identification showed that puree, clear juice and reconstituted juice possessed the similar aromatic profiles with esters as the crucial components contributing the most to the characteristic aroma. Components of secondary importance to the aroma were contributed by the carbonyl fractions, followed by alcohols and hydrocarbons and elemicin. Only four compounds were retained on the surface of the microcapsulated banana powder. Primary component analysis extracted two principal components that exhibit 100% contribution to the total variance of the data set. Aroma profile of banana puree, clear banana juice and the reconstituted banana juice show no significant difference, with esters as the decisive components of the aroma and isoamyl butyrate as the major constituent of the esters, while the compounds responsible for the characteristic aroma were hardly detected from the microcapsulated banana powder, indicating that the main volatile components can be effectively encapsulated through microcapsulation.
Storage stability of the natural colourant from Justicia spicigera microencapsulated in protective colloids blends by spray‐drying
Authors: Pavón‐García Leopoldo Marco Antonio , Pérez‐Alonso César , Orozco‐Villafuerte Juan , Pimentel‐González Diana Jaqueline , Rodríguez‐Huezo María Eva , Vernon‐Carter Eduardo Jaime
Published: June 2011

Muitle (Justicia spicigera), a Mexican native plant, produces a purple aqueous extract (MAE) because of its anthocyanin content. The aim of this work was to microencapsulate MAE by spray‐drying in two different protective colloids blends in a 1:1 weight ratio: gum Arabic‐mesquite gum (GA50‐MD50) and mesquite gum‐maltodextrin DE10 (MG50‐MD50), yielding the microcapsules MGA50‐MD50 and MMG50‐MD50. The minimum integral entropy of the microcapsules was determined at 20, 35 and 40 °C, and the resulting water activities (aW) were 0.555, 0.592, 0.627 for MGA50‐MD50 and 0.581, 0.587, 0.648 for MMG50‐MD50, respectively. These aW temperature sets were considered as the most adequate conditions for achieving maximum storage stability of the microcapsules. Total anthocyanin content (TAC) and total colour change (ΔE) suffered considerable degradation at all storage conditions, but that degradation was significantly inhibited by encapsulating MAE in the biopolymers blends especially that made up by MG50‐MD50.
Family quality of life in 25 Belgian families: quantitative and qualitative exploration of social and professional support domains
Authors: Steel R. , Poppe L. , Vandevelde S. , Van Hove G. , Claes C.
Published: June 2011

Background  This article reports on the results of a study conducted in Belgium on family quality of life situated within a larger project focusing on the development of support strategies for young and adolescent siblings of persons with intellectual disabilities. The objectives of this article are twofold: (1) to present the results of the measures contained in the nine domains of the Family Quality of Life Survey‐2006 (FQOLS‐2006) from the perspective of parents (quantitative analysis); and (2) to come to a more in‐depth understanding of two important domains of the FQOLS‐2006 by exploring and comparing the quantitative and qualitative data from open‐ended interviews with parents.

Method  The FQOLS‐2006 was completed by the main caregivers of 25 families living in one typical Belgian province. Subsequently, semi‐structured interviews with one or both parents were conducted within the same families. Content analysis was carried out on the transcribed interviews using the qualitative software package MaxQDA.

Results  A detailed analysis of the quantitative data together with data from the content analysis of the interviews revealed important issues with regard to two family quality of life domains, support from others and support from services. In general, parents were satisfied with the professional support they received, whereas they were more critical of support from others.

Conclusions  The quantitative data from the FQOLS‐2006 were supported and further explained by the qualitative data. These findings highlight the importance of adequate professional support, which is a flexible and capable answer to each family's individual needs. The authors warn of the dangers of ‘handicapism’ and plea for a family‐centred support approach that takes the whole family into account. Finally, they indicate the benefits of increased practical‐pedagogical support.
Modelling contemporary evolution in stickleback
Authors: RAEYMAEKERS JOOST A.M.
Published: June 2011

During the past decade, two lines of research have advanced our understanding of micro‐evolution. On the one hand, a number of studies have generated evidence for strong selection on phenotypes (Kingsolver et al. 2001) and the contemporary (sometimes deemed ‘rapid’) evolution of phenotypic traits (Hendry & Kinnison 1999). On the other hand, other studies have sought to identify the genes that underlie ecologically important traits (Ungerer et al. 2008). Over the next decade, micro‐evolutionists might expect considerable progress from the study of contemporary evolution at both the phenotypic and genetic level simultaneously. In this issue of Molecular Ecology, Le Rouzic et al. (2011) present a teaser for this approach. They examined contemporary evolution of an adaptive trait with a well‐studied genetic basis, the number of lateral plates, in threespine stickleback (Gasterosteus aculeatus L.). A time series of 20 years of change for this trait after introduction into a pond in Norway was compared with a similar time series of 12 years following the invasion of a lake in Alaska. Using a modelling approach, the authors then teased apart selection acting upon the phenotype and selection acting on a major effect gene. In both time series, selection was strong and consistent. The models suggested that selection could act directly on the phenotype, or through the gene’s pleiotropic effects.
The influence of early environmental exposures on immune development and subsequent risk of allergic disease
Authors: Prescott S. L.
Published: June 2011

To cite this article: Prescott SL. The influence of early environmental exposures on immune development and subsequent risk of allergic disease. Allergy 2011; 66 (Suppl. 95): 4–6.

Environmental exposures in pregnancy and the early postnatal period affect early immune development. Early immune function and future allergy susceptibility appear to result from a combination of maternal phenotype, infant genotype, and environmental exposures in utero that affect early gene expression. Furthermore, epigenetic changes in gene expression in one generation can also be inherited across subsequent generations, potentially amplifying heritable allergy risk.
Infection and the development of allergic disease
Authors: Holt P. G.
Published: June 2011

To cite this article: Holt PG. Infection and the development of allergic disease. Allergy 2011; 66 (Suppl. 95): 13–15.

Persistent allergic diseases exemplified by atopic asthma frequently begin during very early life. Epidemiological findings indicate that progression from allergic sensitization to atopic asthma occurs most frequently when atopy is accompanied by early respiratory viral infections. The underlying mechanism appears to involve recruitment of atopy‐associated effector mechanisms into the host response to the virus. This has the dual effect of antagonising anti‐viral immunity and amplifying inflammation in the infected airway mucosa, driving asthma pathogenesis. Immune responses underlying the allergic state are uniquely plastic during childhood. Alleviating specific allergy during this period may reduce risk of subsequent asthma development.
Anaphylaxis pathogenesis and treatment
Authors: Simons F. Estelle R.
Published: June 2011

To cite this article: Simons FER. Anaphylaxis pathogenesis and treatment. Allergy 2011; 66 (Suppl. 95):31–34.

Anaphylaxis is a serious allergic reaction that is rapid in onset and sometimes leads to death. Understanding mechanisms, triggers, and patient‐specific risk factors for severe or fatal anaphylaxis is critically important. Diagnosis of anaphylaxis is currently based on established clinical criteria. Epinephrine (adrenaline) is the first‐line medication for anaphylaxis treatment and delay in injecting it contributes to biphasic reactions, hypoxic‐ischemic encephalopathy, and fatality. Here, we focus on four important areas of translational research in anaphylaxis: studies of potential new biomarkers to support the clinical diagnosis of anaphylaxis, laboratory tests to distinguish allergen sensitization from clinical risk of anaphylaxis, the primary role of epinephrine (adrenaline) in anaphylaxis treatment, and strengthening the overall evidence base for anaphylaxis treatment.
Treatment of respiratory allergy with allergy immunotherapy tablets
Authors: Bachert C.
Published: June 2011

To cite this article: Bachert C. Treatment of respiratory allergy with allergy immunotherapy tablets. Allergy 2011; 66 (Suppl. 95): 57–59.

Allergy immunotherapy tablets (AIT) have expanded the treatment options for patients suffering from respiratory allergies. Efficacy is established in adults and children for two different commercially available grass AITs. The ALK grass AIT has an efficacy comparable to subcutaneous immunotherapy (SCIT), with a proven disease‐modifying effect after treatment completion. Safety profiles favour AIT over SCIT. Studies suggest that tablets in all aspects are superior to sublingual drops. AITs for other allergies including house dust mite and birch and ragweed pollen are in development.
The future of specific immunotherapy: strategies and challenges for the next generation of allergy vaccines
Authors: Sørensen P.
Published: June 2011

To cite this article: Sørensen P. The future of specific immunotherapy: strategies and challenges for the next generation of allergy vaccines. Allergy 2011; 66 (Suppl. 95): 63–65.

The use of specific immunotherapy (SIT) for allergic disorders has recently been extended by introduction of a convenient, tablet‐based, disease‐modifying vaccine against grass pollen allergy. Allergy immunotherapy tablet (AIT) programmes targeting house dust mite and other allergies are currently in late‐phase development. Next‐generation allergy vaccines can have optimised potency and onset of action without compromising safety or convenience. Key to achieving these objectives is a combination of evidence‐based mode‐of‐action studies and biomarker‐centric translational research approaches. This will rely on using biobank and bioinformatics resources for multi‐omic characterisations of the ‘immunome’ of allergic disease. Other important areas are ongoing paediatric trials and long‐term studies in adults for further defining the potential role of SIT in allergic disease and primary prevention of asthma. Finally, combining cellular‐ and serological‐based assays, and developments in targeted delivery platforms and component‐resolved diagnostics will lead to increased ability to stratify patients, with more personalised diagnosis and treatment.
Current problems of chronic active antibody‐mediated rejection
Authors: Takeda Asami , Horike Keiji , Ohtsuka Yasuhiro , Inaguma Daijo , Goto Norihiko , Watarai Yoshihiko , Uchida Kazuharu , Morozumi Kunio
Published: June 2011

Takeda A, Horike K, Ohtsuka Y, Inaguma D, Goto N, Watarai Y, Uchida K, Morozumi K. Current problems of chronic active antibody‐mediated rejection. Clin Transplant 2011: 25 (Suppl. 23): 2–5. © 2011 John Wiley & Sons A/S.

Abstract:  The Banff 2007 classification allows chronic rejection to be differentiated based on clinicopathological characteristics evidenced by two independent immunologic mechanisms; chronic active antibody‐mediated rejection and chronic active T‐lymphocyte mediated rejection. However, several incompletely understood issues concerning chronic active antibody‐mediated rejection remain. Chronic active antibody‐mediated rejection is characterized by C4d deposition in the capillary basement membrane(PTC), the presence of circulating anti‐donor antibodies(DSA), and morphologic evidence of chronic tissue injury such as glomerular double contours compatible with transplant glomerulopathy (TPG), PTC basement membrane multilayering, interstitial fibrosis/tubular atrophy, and fibrous arterial intimal thickening. PTC basement membrane multilayering correlates highly with TPG, and most of TPG have evidence of either C4d‐positive staining or DSA. However, the proposed criteria do not apply to all situations of chronic active antibody‐mediated rejection. C4d is not a magic marker for antibody‐mediated rejection. C4d staining is not always highly sensitive for detecting antibody‐mediated rejection. Multi‐institutional studies should be conducted to better understand the clinicopathological context of chronic antibody‐mediated rejection. These studies should include well‐designed serial protocol biopsies with evaluation by electron microscopy, C4d staining performed on frozen sections, and assessment using sensitive DSA detection methods.
Transcriptional responses to cantharidin, a protein phosphatase inhibitor, in Arabidopsis thaliana reveal the involvement of multiple signal transduction pathways
Authors: Bajsa Joanna , Pan Zhiqiang , Duke Stephen O.
Published: June 2011

Cantharidin is a natural compound isolated from the blister beetle (Epicauta spp.). It is a potent inhibitor of protein serine/threonine phosphatases (PPPs), especially PP2A and PP4. Protein phosphatases and kinases maintain a sensitive balance between dephosphorylated and phosphorylated forms of appropriate proteins, thereby playing important roles in signal transduction pathways and regulation of gene expression, cellular proliferation, cell differentiation, apoptosis and other processes. The foliage of 12‐day‐old Arabidopsis thaliana seedlings was treated with 200 µM (IC30) of the PPP inhibitor cantharidin, and the entire transcriptome profile was determined by microarray analysis at 2, 10 and 24 h after treatment. The transcription of approximately 10% (2577) of the 24 000 genes of Arabidopsis changed significantly (P≤ 0.05 and signal log ratios: ≥1 or ≤−1) after treatment. Inhibition of PPPs significantly reduced transcription of genes associated with auxin and light signaling and induced expression of genes involved in the hypersensitive response and in flagellin and abscisic acid signaling. The great variety of up‐ and downregulated genes in this microarray experiment implied that cantharidin interfered with the activities of PPPs that interact directly or indirectly with receptors or are located near the beginning of signal transduction pathways. In many cases, PPPs interact with protein complexes of various receptors such as ethylene or light sensors localized in different cell compartments. They function as negative regulators modifying receptor functions, thus altering signaling that influences transcriptional responses.
No evidence for depletion of carbohydrate pools in Scots pine (Pinus sylvestris L.) under drought stress
Authors: Gruber A. , Pirkebner D. , Florian C. , Oberhuber W.
Published: June 2011

The physiological mechanisms leading to Scots pine (Pinus sylvestris L.) decline in the dry inner alpine valleys are still unknown. Testing the carbon starvation hypothesis, we analysed the seasonal course of mobile carbohydrate pools (NSC) of Scots pine growing at a xeric and a dry‐mesic site within an inner alpine dry valley (750 m a.s.l., Tyrol, Austria) during 2009, which was characterised by exceptional soil dryness. Although, soil moisture content dropped to ca. 10% at both sites during the growing season, NSC concentrations rose in all tissues (branch, stem, root) until the end of July, except in needles, where maxima were reached around bud break. NSC concentrations were not significantly different in the analysed tissues at the xeric and the dry‐mesic site. At the dry‐mesic site, NSC concentrations in the aboveground tree biomass were significantly higher during the period of radial growth. An accumulation of NSC in roots at the end of July indicates a change in carbon allocation after an early cessation in aboveground growth, possibly due to elevated belowground carbon demand. In conclusion, our results revealed that extensive soil dryness during the growing season did not lead to carbon depletion. However, even though carbon reserves were not exhausted, sequestration of carbohydrate pools during drought periods might lead to deficits in carbon supply that weaken tree vigour and drive tree mortality.
Characterization of Immunoreactive IGF‐I Pattern During the Peri‐ovulatory Period of the Oestrous Cycle of Thoroughbred Mares and Its Relation to Other Hormones
Authors: Derar DR , Taya K , Watanabe G , Miyake Y‐I
Published: June 2011

Contents

The aim of this study was to characterize ir‐IGF‐I pattern and its relation to other hormones during the oestrous cycle in mares. Nine non‐pregnant non‐lactating pluriparous thoroughbred mares were used. The studied mares were examined ultrasonically and bled daily to follow the ovarian changes and the hormonal milieu for a complete Interovulatory interval (IOI). Two (minor and major) follicular waves were characterized per IOI in thoroughbred mares. The largest follicle of the first follicular wave (DF1) was firstly detected at D – 1.75 ± 0.47 with a growth rate of 2.78 ± 0.14 mm/day and maximum diameter of 22.45 ± 0.75 mm on day 6.65 ± 0.82. The largest follicle of the second follicular wave (DF2) had a growth rate of 2.15 ± 0.29 mm/day, reached a maximum diameter of 42.70 ± 2.63 mm on D 19.25 ± 0.43. Ir‐IGF‐I increased significantly prior to ovulation and had a similar pattern to oestrogen (r = 0.84, p < 0.05), suggesting that the ovarian follicles are the main source of circulating ir‐IGF‐I during the oestrous cycle of mares and that ir‐IGF‐I may be a crucial factor in follicular differentiation and maturation. In conclusion, this study demonstrated that ir‐IGF‐I is secreted during the oestrous phase of the cycle concomitant with the development of the future ovulatory dominant follicle, and it may act in synergy with other hormones for the selection and differentiation of the dominant follicle.
Early weight changes after birth and serum high‐molecular‐weight adiponectin level in preterm infants
Authors: Yoshida Tomohide , Nagasaki Hiraku , Asato Yoshihide , Ohta Takao
Published: June 2011

Background:  Extra‐uterine growth retardation (EUGR) is associated with an increased risk for cardiometabolic diseases later in life. The aim of the present study was to examine the relationship between early weight change after birth in preterm infants and adiponectin (adn) multimeric complexes.

Methods:  Subjects included 28 preterm infants born between weeks 24 and 33 of gestation. Serum adn multimeric complexes and the anthropometric parameters were measured in preterm infants at birth and at corrected term.

Results:  Bodyweight (BW) decreased during the first week of life, with birthweight restored at approximately 19 days after birth. Nineteen of the subjects had EUGR at corrected term. Total (T)‐adn, high‐molecular‐weight (H)‐adn, and the ratio of H‐adn to T‐adn (H/T‐adn) were significantly elevated at corrected term than at birth. Postmenstrual age, birthweight, birth length and lowest BW after birth were positively correlated with H‐adn and H/T‐adn. Weight reduction after birth was negatively correlated with H‐adn. Age to restore birthweight was negatively correlated with T‐adn, H‐adn and H/T‐adn. Stepwise multiple regression analysis indicated age to restore birthweight as the major predictor of T‐adn and H‐adn.

Discussion:  Early weight changes after birth may alter serum adn level in preterm infants at corrected term. The appropriate nutritional support in the early postnatal period could reduce the prevalence of EUGR and the future risk for cardiometabolic diseases.
Toxicity of local anesthetic drugs: a pediatric perspective
Authors: Lönnqvist Per‐Arne
Published: June 2011

The main mechanism of action of local anesthetics (LA) is to block sodium channels, thereby interrupting the propagation of nerve impulses. However, this action not only is localized to the sodium channels of nerve tissues involved with pain transmission but will have its effect on any tissue containing sodium channels. Thus, if there is a rapid absorption into the systemic circulation of locally injected LA or if LA inadvertently is injected into a blood vessel, then significant blockade of sodium channels in other tissues may also be blocked and serious complications may ensue. The two most important tissues associated with systemic toxicity of LA are the central nervous and the cardiovascular systems, which may lead to seizures, tachyarrhythmias, and ultimately death from apnea and cardiovascular collapse. The aim of this communication is to elucidate some issues that are associated with toxicity of LA and its treatment in the pediatric population.
The incommensurability of nursing as a practice and the customer service model: an evolutionary threat to the discipline
Authors: Austin Wendy J.
Published: June 2011

Corporate and commercial values are inducing some healthcare organizations to prescribe a customer service model that reframes the provision of nursing care. In this paper it is argued that such a model is incommensurable with nursing conceived as a moral practice and ultimately places nurses at risk. Based upon understanding from ongoing research on compassion fatigue, it is proposed that compassion fatigue as currently experienced by nurses may not arise predominantly from too great a demand for compassion, but rather from barriers to enacting compassionate care. These barriers are often systemic. The paradigm shift in which healthcare environments are viewed as marketplaces rather than moral communities has the potential to radically affect the evolution of nursing as a discipline.
Maths for medications: an analytical exemplar of the social organization of nurses' knowledge
Authors: Dyjur Louise , Rankin Janet , Lane Annette
Published: June 2011

Within the literature that circulates in the discourses organizing nursing education, there are embedded assumptions that link student performance on maths examinations to safe medication practices. These assumptions are rooted historically. They fundamentally shape educational approaches assumed to support safe practice and protect patients from nursing error. Here, we apply an institutional ethnographic lens to the body of literature that both supports and critiques the emphasis on numeracy skills and medication safety. We use this form of inquiry to open an alternate interrogation of these practices. Our main argument posits that numeracy skills serve as powerful distraction for both students and teachers. We suggest that they operate under specious claims of safety and objectivity. As nurse educators, we are captured by taken‐for‐granted understandings of practices intended to produce safety. We contend that some of these practices are not congruent with how competency actually unfolds in the everyday world of nursing practice. Ontologically grounded in the materiality of work processes, we suggest there is a serious disjuncture between educators' assessment and evaluation work where it links into broad nursing assumptions about medication work. These underlying assumptions and work processes produce contradictory tensions for students, teachers and nurses in direct practice.