bluuebunny/crossref_metadata_2025 huggingface dataset:
Extending Cassava Root Shelf Life via Reduction of Reactive Oxygen Species Production
Authors: Zidenga Tawanda , Leyva-Guerrero Elisa , Moon Hangsik , Siritunga Dimuth , Sayre Richard
Published: June 2012

One of the major constraints facing the large-scale production of cassava (Manihot esculenta) roots is the rapid postharvest physiological deterioration (PPD) that occurs within 72 h following harvest. One of the earliest recognized biochemical events during the initiation of PPD is a rapid burst of reactive oxygen species (ROS) accumulation. We have investigated the source of this oxidative burst to identify possible strategies to limit its extent and to extend cassava root shelf life. We provide evidence for a causal link between cyanogenesis and the onset of the oxidative burst that triggers PPD. By measuring ROS accumulation in transgenic low-cyanogen plants with and without cyanide complementation, we show that PPD is cyanide dependent, presumably resulting from a cyanide-dependent inhibition of respiration. To reduce cyanide-dependent ROS production in cassava root mitochondria, we generated transgenic plants expressing a codon-optimized Arabidopsis (Arabidopsis thaliana) mitochondrial alternative oxidase gene (AOX1A). Unlike cytochrome c oxidase, AOX is cyanide insensitive. Transgenic plants overexpressing AOX exhibited over a 10-fold reduction in ROS accumulation compared with wild-type plants. The reduction in ROS accumulation was associated with a delayed onset of PPD by 14 to 21 d after harvest of greenhouse-grown plants. The delay in PPD in transgenic plants was also observed under field conditions, but with a root biomass yield loss in the highest AOX-expressing lines. These data reveal a mechanism for PPD in cassava based on cyanide-induced oxidative stress as well as PPD control strategies involving inhibition of ROS production or its sequestration.
Revival of Palaeoptera—head characters support a monophyletic origin of Odonata and Ephemeroptera (Insecta)
Authors: Blanke Alexander , Wipfler Benjamin , Letsch Harald , Koch Markus , Beckmann Felix , Beutel Rolf , Misof Bernhard
Published: June 2012

The earliest branching event in winged insects, one of the core problems regarding early insect evolution, was addressed using characters of the head. The head is arguably one of the most complex body regions in insects and the phylogenetic information content of its features has been demonstrated. In contrast, the wings and other body parts related to the flight apparatus and sperm transmission are not useful in the context of this problem, as the outgroups (silverfish and bristletails) are wingless and transmit spermatophores externally. Therefore, they show profound differences in the organization of the postcephalic body, and assessment of homology and subsequent phylogenetic analysis of features of these body regions is extremely difficult. The core of this study is the investigation of head structures of representatives of the major clades of dragonflies. A detailed description of the head of Lestes virens is presented and was used as a starting point for the compilation of a character set and a character state matrix for the entire Dicondylia (winged insects + silverfish), with a main focus on the placement of dragonflies and consequently the basal branching event within winged insects. Our results indicate a sister‐group relationship between a clade Palaeoptera (dragonflies + mayflies) and the megadiverse monophyletic lineage Neoptera. We show that despite considerable structural similarity between the odonate and neopteran mandible, the muscle equipment in dragonflies is more plesiomorphic with respect to Dicondylia than previously known. Odonata and Ephemeroptera also share presumably derived features of the antenna, maxilla, and labial musculature. Parsimony analyses of the head data unambiguously support a clade Palaeoptera.

© The Willi Hennig Society 2012.
Male‐killer dynamics inDanaus chrysippus(L.) (Lepidoptera:Nymphalidae) inEastAfrica
Authors: Hassan Sami S. M. , Idris Eihab , Majerus Michael E. N.
Published: June 2012

Within certain regions in East Africa, the butterflyDanaus chrysippus(L.) shows female‐biased population sex ratio, because of the production by some females of all‐female broods, as a result of infection by maternally inherited, male‐killing bacterium of the genusSpiroplasma. In this study, we describe a 3‐year field survey for the population dynamics of the male‐killingSpiroplasmainD. chrysippusin four independent localities, namelyUganda,Ghana,Sudan andMadagascar. The prevalence of the bacterium was found to show extensive variations at multiple scales among different sites, in various countries, seasons and years. A novel, selection‐based hypothesis was suggested to explain the high variability of male‐killer prevalence over space and time, based on the existence of an adaptive link between larval food‐plant density and the magnitude of resource reallocation fitness advantage for the male‐killer.
Low doses of fludrocortisone and hydrocortisone, alone or in combination, on vascular responsiveness to phenylephrine in healthy volunteers
Authors: Laviolle Bruno , Donal Erwan , Le Maguet Pascale , Lainé Fabrice , Bellissant Eric
Published: June 2012

Aims

A single administration of hydrocortisone has been shown to enhance the pressor response to phenylephrine in healthy volunteers and to norepinephrine in septic shock patients. Similar data do not exist for fludrocortisone. Since there continues to be disagreement about the utility of fludrocortisone in septic shock, we assessed the effects of a single administration of low doses of hydrocortisone (50 mg intravenously) and fludrocortisone (50 μg orally), given either alone or in combination, on phenylephrine mean arterial pressure and cardiac systolic and diastolic function dose–response relationships in 12 healthy male volunteers with hypo‐aldosteronism induced by intravenous sodium loading.

Methods

This was a placebo‐controlled, randomized, double‐blind, crossover study performed according to a 2 × 2 factorial design. Subjects received first a 2000 ml infusion of NaCl 0.9% during 2 h. Then fludrocortisone 50 μg (or its placebo) was administered orally and hydrocortisone 50 mg (or its placebo) was injected intravenously. At 1.5 h after treatment administration, incremental doses of phenylephrine were infused (from 0.01 to 3 μg kg−1 min−1), each dose being infused during 5 min.

Results

Both fludrocortisone (P < 0.001) and hydrocortisone (P = 0.002) induced a significant decrease in pressor response to phenylephrine, their effects being additive (fludrocortisone × hydrocortisone interaction, P = 0.792). The two drugs did not induce any detectable cardiac effect.

Conclusions

Single administrations of fludrocortisone and hydrocortisone decreased the pressor response to phenylephrine in healthy volunteers with hypo‐aldosteronism. These similar effects of hydrocortisone and fludrocortisone probably express a rapid non‐genomic vasodilating effect of the two steroids in the context of acute volume loading.
In papillary thyroid carcinoma BRAFV600E is associated with increased expression of the urokinase plasminogen activator  and its cognate receptor, but not with disease‐free interval
Authors: Ulisse Salvatore , Baldini Enke , Sorrenti Salvatore , Barollo Susi , Prinzi Natalie , Catania Antonio , Nesca Angela , Gnessi Lucio , Pelizzo Maria R. , Mian Caterina , De Vito Corrado , Calvanese Anna , Palermo Silvio , Persechino Severino , De Antoni Enrico , D'Armiento Massimino
Published: June 2012

Context

It has been suggested that patients with papillary thyroid cancer (PTC) harbouring the BRAFV600E mutation have a worse prognosis. We showed in PTC that high levels of urokinase plasminogen activator (uPA) and its cognate receptor (uPAR) inversely correlate with disease‐free interval (DFI).

Objectives

To investigate the effects of BRAFV600E on the expression of uPA and uPAR and to evaluate the prognostic relevance of BRAFV600E alone or in combination with uPA and uPAR.

Design/Setting/Patients/Intervention

The case study included 91 patients with PTC. All patients underwent thyroidectomy and radioiodine therapy. Follow‐up was available for 75 patients.

Main outcome measures

The BRAFV600E mutation was analysed by sequencing and mutant allele‐specific PCR amplification; uPA and uPAR expression by quantitative RT‐PCR.

Results

BRAFV600E was found in 44 of the 91 patients and associated with older age, but not with high‐risk clinicopathological features. Urokinase PA and uPAR mRNA levels were higher in tumour tissues by 9·51 ± 1·30 and 4·64 ± 0·44 fold, respectively, compared to normal matched tissues, being significantly higher in BRAFV600E‐positive patients. In vitro induction of BRAFV600E in PCCL3 cells caused a significant increase in both uPA and uPAR mRNAs. Higher levels of uPA and uPAR correlated with lymph node metastases, TNM stage and disease recurrences. Kaplan–Meier and multivariate analyses demonstrated that uPA and uPAR were associated with shorter DFI, while the BRAFV600E was not.

Conclusion

In PTC, BRAFV600E induces uPA and uPAR expression. The latter, but not BRAFV600E, associates with advanced stages and shorter DFI. If confirmed in larger case studies, they may represent reliable prognostic markers for more accurate risk stratification and postoperative decision‐making in patients with PTC.
Lack of sensitivity of the 1‐μg low‐dose ACTH stimulation test in a paediatric population with suboptimal cortisol responses to insulin‐induced hypoglycaemia
Authors: O'Grady Michael J. , Hensey Conor , Fallon Miriam , Hoey Hilary , Murphy Nuala , Costigan Colm , Cody Declan
Published: June 2012

Context

The insulin‐tolerance test (ITT) is the gold standard for evaluation of the hypothalamic‐pituitary‐adrenal (HPA) axis. The low‐dose ACTH stimulation test is increasingly used for evaluation of secondary adrenal insufficiency as several studies performed in adults have demonstrated high sensitivity and specificity when compared to the ITT. Whether the ACTH stimulation test demonstrates similar sensitivity in a paediatric and adolescent population compared with the gold standard is unclear.

Objective

To compare the sensitivity of the low‐dose (1‐μg) Synacthen™ test (LDSST) and the gold‐standard ITT in a paediatric and adolescent population.

Design and Patients

A retrospective review of 42 consecutive LDSSTs in children and adolescents with suboptimal cortisol responses (peak <500 nm) on ITT.

Results

Thirty‐one patients (74%) had an adequate cortisol response to low‐dose Synacthen™ (sensitivity 26%). Patients had a higher cortisol increment with the LDSST than ITT (median Δ cortisol 294 vs 168 nm, P < 0·0001) and correspondingly a higher cortisol peak (median peak cortisol 572 vs 396 nm, P < 0·0001). Patients who had a suboptimal peak cortisol both on ITT and on LDSST had a lower baseline cortisol on ITT (median 178 vs 227 nm, P = 0·04). Peak cortisol on ITT was significantly higher in patients who had a subsequent normal LDSST than those that did not (median 417 vs 300 nm, P = 0·0005).

Conclusions

The 1‐μg LDSST lacks sensitivity in detection of secondary adrenal insufficiency in children when compared to the gold‐standard ITT.
The roles of dispersal limitation and environmental conditions in controlling caddisfly (Trichoptera) assemblages
Authors: LANDEIRO VICTOR LEMES , BINI LUIS MAURICIO , MELO ADRIANO SANCHES , PES ANA MARIA OLIVEIRA , MAGNUSSON WILLIAM ERNEST
Published: June 2012

1. Many recent studies have quantified the relative importance of environmental variables and dispersal limitations in shaping the structure of stream communities. However, the relative importance of these factors at different spatial extents has been seldom evaluated.

2. We analysed the distribution of caddisfly species in 89 Amazonian streams in relation to stream characteristics and spatial variables representing overland dispersal routes. The streams occur in three regions that differ in spatial extent and environmental characteristics. We analysed the data using partial redundancy analysis with two predictor data sets, one environmental and one spatial, to evaluate the variation in assemblage composition. We also separated caddisflies into ‘good’ and ‘poor’ dispersers to evaluate possible differences in the responses of these two groups.

3. The environmental component explained a higher proportion of variance in assemblage composition than did the spatial component. Spatial effects were evident only when data from all three regions were analysed together, although the exclusive spatial fraction was quite low. Good dispersers responded similarly to the community as a whole, while poor dispersers were related to environmental variables only in one region and also were not related to spatial variables.

4. Caddisflies were most affected by environmental factors. The large environmental effect and small spatial effect are in accord with the use of these stream insects as good indicators of site properties and disturbances in monitoring programmes.
Odour‐active compounds in mango (Mangifera indica L. cv. Corazón)
Authors: Pino Jorge A.
Published: June 2012

Simultaneous distillation–extraction combined with GC‐FID and GC‐MS were used to analyse volatile compounds from mango (Mangifera indica L. cv. Corazón) and to estimate the most odour‐active compounds in the fruit. The analyses led to the identification of 167 components, from which 128 were positively identified. The aroma‐active areas in the gas chromatogram were screened by the application of the aroma extract dilution analysis and by odour activity values. Eighteen odorants were considered as the most odour‐active compounds: (E)‐β‐damascenone, ethyl butanoate, (E,Z)‐nonadienal, ethyl 2‐methylpropanoate, (E)‐2‐nonenal, (E)‐β‐ionone, terpinolene, δ‐3‐carene, β‐caryophyllene, ethyl 2‐methylbutanoate, limonene, myrcene, linalool, γ‐octalactone, nonanal, methyl benzoate, 2,5‐dimethyl‐4‐methoxy‐3(2H)‐furanone and hexanal.
Ozonation of corn and potato starch in aqueous solution: effects on the thermal, pasting and structural properties
Authors: Çatal Hatice , İbanoğlu Şenol
Published: June 2012

Starch–water suspensions were exposed to ozone gas for 1 h at 5 °C. The concentration of dissolved ozone gas in the suspension was kept at 4.2 mg ozone/L−1 water. Polarised light and scanning electron microscope (SEM) were used to examine the birefringence and surface characteristics of the samples, respectively. A differential scanning calorimeter (DSC) was used to measure the gelatinisation properties, while a rapid visco analyser (RVA) was used to examine pasting properties. The structure of corn and potato starch showed very little change after treatment with ozonated water. The DSC gelatinisation temperatures (i.e. onset, peak and conclusion) of starch samples increased as a result of ozonation. However, a decrease in gelatinisation enthalpies was observed for ozonated starch samples. A dramatic decrease in the RVA viscosities of ozonated starch samples was observed after ozonation, which are explained by the partial cleavage of the glycosidic linkages in the starch granules during ozonation.
Influences of food matrices on cytotoxicity of asiatic acid in mammalian cell models
Authors: Jirasripongpun Kalyanee , Jirakanjanakit Nuananong , Sakulsom Premwadee , Wongekalak La‐ongdao , Hongsprabhas Parichat
Published: June 2012

This study investigated the cytotoxicity of asiatic acid (AA) encapsulated in different protein‐carbohydrate matrices in human colon adenocarcinoma SW620, human hepatoblastoma HepG2 and diploid monkey kidney cells (Vero). Mungbean protein concentrate (MPC) and mungbean protein hydrolysate (MPH) in lactose (L) or lactose‐maltodextrin (LM) mixture, were used to fabricate matrices encapsulating AA during lyophilisation. The cytotoxicity of AA was in a dose‐dependent manner for HepG2 and SW620 cells, but not for Vero cells. The 50% inhibitory concentrations (IC50) of AA in HepG2 and SW620 were 120 and 130 μm respectively. The IC50 of AA encapsulated in MPH‐L matrix in HepG2 was reduced from that of AA alone to 80 μm (P < 0.05). Study of the anti‐cancer activity of AA, in the absence and presence of food matrices, revealed that an MPH‐L matrix led AA to cause more apoptosis deaths in HepG2 cells than either a MPC‐L matrix or pure AA.
Cardiac rehabilitation and the therapeutic environment: the importance of physical, social, and symbolic safety for programme participation among women
Authors: Sutton Erica J. , Rolfe Danielle E. , Landry Mireille , Sternberg Leonard , Price Jennifer A.D.
Published: June 2012

Sutton E.J., Rolfe D.E., Landry M., Sternberg L. & Price J.A.D. (2012) Cardiac rehabilitation and the therapeutic environment: the importance of physical, social, and symbolic safety for programme participation among women. Journal of Advanced Nursing68(6), 1834–1846.

Aim.  To report an exploration of the multidimensionality of safety in cardiac rehabilitation programmes as perceived by women who were enrolled in the Women’s Cardiovascular Health Initiative in Toronto, Canada.

Background.  Cardiovascular disease is the leading cause of death among women. Although cardiac rehabilitation is clinically effective, significantly fewer women than men participate in available programmes. The literature identifies factors affecting women’s cardiac rehabilitation participation, and provides possible explanations for this gender disparity. Although safety is mentioned among the barriers to women’s cardiac rehabilitation participation, the extent to which safety contributes to programme participation, completion, and maintenance remains under‐explored in the cardiac rehabilitation literature.

Design.  We conducted an exploratory qualitative study to examine the role safety and place play for women engaged in cardiac prevention and rehabilitation at the Women’s Cardiovascular Health Initiative.

Methods.  From 2005–2006, 14 participants engaged in semi‐structured, qualitative interviews lasting 30–90 minutes. Discussions addressed women’s experiences at the Women’s Cardiovascular Health Initiative. Interview transcripts were analysed using thematic analysis.

Findings.  Three themes were developed: ‘Safety’, which was sub‐categorized according to physical, social, and symbolic interpretations of safety, ‘searching for a sense of place’, and ‘confidence and empowerment’.

Conclusion.  Feeling physically, socially, and symbolically safe in one’s cardiac rehabilitation environment may contribute to programme adherence and exercise maintenance for women. Focusing on comprehensive notions of safety in future cardiac rehabilitation research could offer insight into why many women do not maintain an exercise regimen in currently structured cardiac rehabilitation and community programmes.
Humidity levels drive reproductive modes and phylogenetic diversity of amphibians in the Brazilian Atlantic Forest
Authors: da Silva Fernando Rodrigues , Almeida‐Neto Mário , do Prado Vitor Hugo Mendonça , Haddad Célio Fernando Baptista , de Cerqueira Rossa‐Feres Denise
Published: June 2012

Aim  The diversity of reproductive modes among amphibians constitutes a striking example of how differences in the biology of species provide important explanations for species distribution patterns on a broad scale. We hypothesize that sites with a higher humidity level will support more modes of reproduction than drier sites and will consequently exhibit a higher phylogenetic diversity. Furthermore, if there is a gradient in the tolerance of reproductive modes to desiccation, there will be a nested pattern in the composition of reproductive modes among sites.

Location  Twenty‐seven forest sites in the Brazilian Atlantic Forest.

Methods  Through a path analysis approach, we evaluated the direct and indirect effects of the humidity level on the number of reproductive modes, as well as the relative importance of both variables on amphibian phylogenetic diversity. A nestedness analysis was used to quantify the extent to which the compositions of both species and reproductive modes in drier sites correspond to subsets of those in sites with higher annual precipitation.

Results  We found that the reproductive modes present in drier sites are non‐random subsets of those present in sites with higher humidity levels. Because reproductive modes are phylogenetically conserved among amphibians, sites with a greater number of reproductive modes supported greater phylogenetic diversity. Sites with high precipitation throughout the year provided suitable environmental conditions for a larger number of reproductive modes, whereas sites with low precipitation and typical seasonal climates supported only those reproductive modes specialized to resist desiccation.

Main conclusions  Our results show that humidity‐related variables are key environmental factors related to both the richness of reproductive modes and phylogenetic diversity. Our results support the hypothesis that the higher phylogenetic diversity found in moister sites reflects differences in the tolerance to desiccation among different reproductive modes. Given that reproductive modes are associated with susceptibility to desiccation, their incorporation into explanatory models may trigger a significant advance in the understanding of the mechanisms regulating the species richness and composition of amphibian communities.
RHO1 and RHO2 share partially overlapping functions in the regulation of cell wall integrity and hyphal polarity in Neurospora crassa
Authors: Richthammer Corinna , Enseleit Matthias , Sanchez‐Leon Eddy , März Sabine , Heilig Yvonne , Riquelme Meritxell , Seiler Stephan
Published: June 2012

Rho proteins are key regulators of cellular morphogenesis, but their function in filamentous fungi is poorly understood. By generating conditional rho‐1 mutants, we dissected the function of the essential GTPase RHO1 in cell polarization and maintenance of cell wall integrity in Neurospora crassa. We identified NCU00668/RGF1 as RHO1‐specific exchange factor, which controls actin organization and the cell wall integrity MAK1 MAP kinase pathway through the direct interaction of active RHO1 with the formin BNI1 and PKC1 respectively. The activity of RGF1 is controlled by an intramolecular interaction of its DEP and GEF domains that blocks the activation of the GTPase. Moreover, the N‐terminal region including the DEP domain of RGF1 interacts with the plasma membrane sensor NCU06910/WSC1, potentially to activate the cell wall integrity pathway. RHO1 also functions as regulatory subunit of the glucan synthase. N. crassa possesses a second GTPase, RHO2, that is highly homologous to RHO1. RHO2 is of minor importance for growth and does not interact with BNI1. Conditional rho‐1;rho‐2 double mutants display strong synthetic growth and cell polarity defects. We show that RHO2 does not regulate glucan synthase activity and the actin cytoskeleton, but physically interacts with PKC1 to regulate the cell wall integrity pathway.
National audit of the use of fibrinogen concentrate to correct hypofibrinogenaemia
Authors: Gollop N. D. , Chilcott J. , Benton A. , Rayment R. , Jones J. , Collins P. W.
Published: June 2012

Background

Massive haemorrhage occurs in a variety of clinical settings resulting in consumptive and dilutional coagulopathies leading to hypofibrinogenaemia.

Methods/Materials

A prospective observational national cohort study was performed between November 2008 and June 2010 to collect safety data on the off‐label use of a fibrinogen concentrate to treat acquired hypofibrinogenaemia.

Results

A prospective cohort of 63 patients with varying causes of hypofibrinogenaemia resulted from this data collection. A single infusion of fibrinogen concentrate was given in 49 (77%) of patients studied and 12 received more than one infusion. The median inter‐quartile range (IQR) dose of fibrinogen infused was 49 (26–61) mg kg−1. The median (IQR) fibrinogen level before and after infusion was 0·9 (0·6–1·3) and 1·8 (1·4–4·3) g L−1, respectively (P < 0·001). In 31 patients (67%), bleeding stopped within 4 h and fibrinogen was reported to have contributed to this outcome by the treating clinicians. In 84% of cases the treating clinician reported that the use of fibrinogen concentrate reduced the rate of bleeding. Fibrinogen was associated with a statistically significant reduction in red blood cell transfusion (median 4 units before and 0 units after, P < 0·001) and fresh frozen plasma infusion (median 4 units before and 0 units after, P < 0·001). Three venous and one arterial non‐fatal thrombotic events were recorded in the patients treated with fibrinogen.

Conclusion

Fibrinogen concentrate can be used to correct hypofibrinogenaemia and may reduce blood product usage.
On the intersections of basic and applied research in xenotransplantation*
Authors: Dalmasso Agustin P.
Published: June 2012

Dalmasso AP. On the intersections of basic and applied research in xenotransplantation. Xenotransplantation 2012; 19: 137–143. © 2012 John Wiley & Sons A/S.

Abstract:  I am very grateful to the Council and members of the International Xenotransplantation Association for this Honorary Membership. In accepting this prestigious award, I pay tribute to my mentors Antonio Oriol i Anguera, Carlos Martinez, Robert A. Good, and Hans Müller‐Eberhard for their guidance and friendship as I was beginning my travels in biomedical research. I also thank the many gifted collaborators, students, and technical personnel, as well as the agencies and taxpayers, who funded our research and made our scientific contributions possible. Here I briefly mention some of these contributions, including early work on the immunobiology of the thymus, my short incursion in the immunology of Chagas disease, and what have been the dominant themes of my career: the mechanisms of complement injury, the role of complement in pathophysiology, and induction of cytoprotection in the vascular endothelium. I emphasize our contributions on the role of complement as related to understanding and overcoming xenograft injury, a work that has been personally very rewarding. Now it is exciting to see that the field of xenotransplantation research is moving forward vigorously, a time of great optimism suggesting that many potential clinical applications of xenotransplantation will come to fruition in the near future.
Clinical lung xenotransplantation – what donor genetic modifications may be necessary?
Authors: Cooper David K. C. , Ekser Burcin , Burlak Christopher , Ezzelarab Mohamed , Hara Hidetaka , Paris Leela , Tector A. Joseph , Phelps Carol , Azimzadeh Agnes M. , Ayares David , Robson Simon C. , Pierson Richard N.
Published: June 2012

Cooper DKC, Ekser B, Burlak C, Ezzelarab M, Hara H, Paris L, Tector AJ, Phelps C, Azimzadeh AM, Ayares D, Robson SC, Pierson RN III. Clinical lung xenotransplantation – what donor genetic modifications may be necessary? Xenotransplantation 2012; 19: 144–158. © 2012 John Wiley & Sons A/S.

Abstract:  Barriers to successful lung xenotransplantation appear to be even greater than for other organs. This difficulty may be related to several macro anatomic factors, such as the uniquely fragile lung parenchyma and associated blood supply that results in heightened vulnerability of graft function to segmental or lobar airway flooding caused by loss of vascular integrity (also applicable to allotransplants). There are also micro‐anatomic considerations, such as the presence of large numbers of resident inflammatory cells, such as pulmonary intravascular macrophages and natural killer (NK) T cells, and the high levels of von Willebrand factor (vWF) associated with the microvasculature. We have considered what developments would be necessary to allow successful clinical lung xenotransplantation. We suggest this will only be achieved by multiple genetic modifications of the organ‐source pig, in particular to render the vasculature resistant to thrombosis. The major problems that require to be overcome are multiple and include (i) the innate immune response (antibody, complement, donor pulmonary and recipient macrophages, monocytes, neutrophils, and NK cells), (ii) the adaptive immune response (T and B cells), (iii) coagulation dysregulation, and (iv) an inflammatory response (e.g., TNF‐α, IL‐6, HMGB1, C‐reactive protein). We propose that the genetic manipulation required to provide normal thromboregulation alone may include the introduction of genes for human thrombomodulin/endothelial protein C‐receptor, and/or tissue factor pathway inhibitor, and/or CD39/CD73; the problem of pig vWF may also need to be addressed. It would appear that exploration of every available therapeutic path will be required if lung xenotransplantation is to be successful. To initiate a clinical trial of lung xenotransplantation, even as a bridge to allotransplantation (with a realistic possibility of survival long enough for a human lung allograft to be obtained), significant advances and much experimental work will be required. Nevertheless, with the steadily increasing developments in techniques of genetic engineering of pigs, we are optimistic that the goal of successful clinical lung xenotransplantation can be achieved within the foreseeable future. The optimistic view would be that if experimental pig lung xenotransplantation could be successfully managed, it is likely that clinical application of this and all other forms of xenotransplantation would become more feasible.
Taste uncoupled from nutrition fails to sustain the reinforcing properties of food
Authors: Beeler Jeff A. , McCutcheon James E. , Cao Zhen F. H. , Murakami Mari , Alexander Erin , Roitman Mitchell F. , Zhuang Xiaoxi
Published: June 2012

Recent findings suggest the reward system encodes metabolic value independent of taste, provoking speculation that the hedonic value of taste could be derived from nutritional value as a secondary appetitive property. We therefore dissociated and compared the impact of nutrition and taste on appetitive behavior in several paradigms. Though taste alone induces preference and increased consumption, in the absence of nutritional value its reinforcing properties are greatly diminished and it does not, like sucrose, induce increased responding over time. In agreement with behavioral data, saccharin‐evoked (but not sucrose‐evoked) dopamine release is greatly attenuated following pre‐exposure, suggesting that nutritional value is critical for dopamine‐mediated reward and reinforcement. Further supporting the primacy of nutrition over taste, genetically increased dopaminergic tone enhances incentive associated with nutritional value with minimal impact on taste‐based, hedonic incentive. Overall, we suggest that the sensory‐hedonic incentive value associated with taste functions as a conditioned stimulus that requires nutritional value to sustainably organize appetitive behavior.
Altered cell cycle‐related gene expression in brain and lymphocytes from a transgenic mouse model of Alzheimer’s disease [amyloid precursor protein/presenilin 1 (PS1)]
Authors: Esteras Noemí , Bartolomé Fernando , Alquézar Carolina , Antequera Desireé , Muñoz Úrsula , Carro Eva , Martín‐Requero Ángeles
Published: June 2012

Cumulative evidence indicates that aberrant re‐expression of many cell cycle‐related proteins and inappropriate neuronal cell cycle control are critical events in Alzheimer’s disease (AD) pathogenesis. Evidence of cell cycle activation in post‐mitotic neurons has also been observed in murine models of AD, despite the fact that most of these mice do not show massive loss of neuronal bodies. Dysfunction of the cell cycle appears to affect cells other than neurons, as peripheral cells, such as lymphocytes and fibroblasts from patients with AD, show an altered response to mitogenic stimulation. We sought to determine whether cell cycle disturbances are present simultaneously in both brain and peripheral cells from the amyloid precursor protein (APP)/presenilin 1 (PS1) mouse model of AD, in order to validate the use of peripheral cells from patients not only to study cell cycle abnormalities as a pathogenic feature of AD, but also as a means to test novel therapeutic approaches. By using cell cycle pathway‐specific RT2Profiler™ PCR Arrays, we detected changes in a number of cell cycle‐related genes in brain as well as in lymphocytes from APP/PS1 mice. Moreover, we found enhanced 5′‐bromo‐2′‐deoxyuridine incorporation into DNA in lymphocytes from APP/PS1 mice, and increased expression of the cell proliferation marker proliferating cell nuclear antigen (PCNA), and the cyclin‐dependent kinase (CDK) inhibitor Cdkn2a, as detected by immunohistochemistry in cortical neurons of the APP/PS1 mice. Taken together, the cell cycle‐related changes in brain and blood cells reported here support the mitosis failure hypothesis in AD and validate the use of peripheral cells as surrogate tissue to study the molecular basis of AD pathogenesis.
The passive and active contractile properties of the neurogenic, underactive bladder
Authors: Young John S. , Johnston Louise , Soubrane Camille , McCloskey Karen D. , McMurray Gordon , Eccles Rachel , Fry Christopher H.
Published: June 2012

What's known on the subject? and What does the study add?

Detrusor underactivity is highly prevalent, particularly in the elderly. It is assumed to result from detrusor failure, although detrusor contractility is often derived from urodynamics studies. Given that detrusor pressure and force are not proportional and urodynamics cannot identify the basis of the pathology, we produced a neurogenic animal model with a highly‐compliant bladder and studied detrusor muscle properties, aiming to increase our understanding of the underlying pathology.

Highly compliant bladders were characterized by reduced passive wall stiffness and stretched detrusor muscle strips exhibited an enhanced rate of relaxation. These detrusor strips displayed spontaneous contractions that were of greater amplitude (expressed as a ratio of bladder wall stiffness) than those of strips from sham‐operated animals; spontaneous contractions increased in amplitude when stimulated by an agonist. These data imply that compliance is not the result of a reduction of detrusor contractility; we hypothesize that altered matrix properties reduce the magnitude with which force can be generated to void the bladder.

Objective

To characterize passive and active changes in detrusor activity in a highly compliant bladder.

Materials and Methods

Bladders from adult female Sprague–Dawley rats were used 5 weeks after lower thoracic (T8) spinal cord transection or a sham‐operation.

Passive wall properties were assessed by pressure–volume relationships from whole bladders and the tensile response of bladder strips after a rapid (<0.5 s) stretch.

Active properties were assessed from the frequency and amplitude of spontaneous contractions of bladder strips, and their response to the inotropic TRPV4 agonist GSK1016790A.

Results

Passive bladder wall stiffness of SCT bladders was significantly reduced compared to that of the sham‐operated control group (N = 6 and 8, respectively) and SCT bladder strips relaxed more quickly than those from sham‐operated rats.

The frequency of spontaneous contractions was reduced in SCT rats, and their amplitude, expressed as a ratio of bladder wall stiffness, was greater than in sham‐operated rats.

GSK1016790A (0.1 μM) significantly increased amplitude in strips from both sham‐operated and SCT groups.

Conclusions

There is no evidence of contractile failure in a highly‐compliant bladder. The observations of reduced passive bladder wall stiffness and an enhanced rate of stress relaxation lead to the conclusion that increased compliance is marked by altered matrix properties that dissipate muscle force, thereby generating low pressures.

Contractile agonists may be effective for improving bladder function in detrusor underactivity.
Implementing the SENCo system in Hong Kong: an initial investigation
Authors: Poon‐McBrayer Kim Fong
Published: June 2012

Monitoring mechanisms of support services for students with special needs can be broadly classified as external and internal. Resembling the UK model, Hong Kong has adopted an internal mechanism through the establishment of the SENCo post. This investigation, written by Dr Kim Fong Poon‐McBrayer, of the Hong Kong Institute of Education, explores how SENCos understand the policy intention of their roles, what the role entails in practice, and what work conditions are usual for participants. This qualitative study involved semi‐structured interviews to probe SENCos' experiences. Findings reveal that SENCos assume management but not leadership roles in special educational needs provision. Policy deviation, and the prevalent autocratic leadership style across schools in Hong Kong, are the key contributors to conditions seen as unsatisfactory, of overwork, of the inadequate planning of provision, and of the need for professional and clerical support. It is concluded that policymakers can make improvements through implementing practical training in participatory governance for headteachers, developing a training model for SENCos, and providing SENCos with additional personnel resources. Further studies to gain a fuller picture of the organisational contexts are recommended.
A BUSINESS TOUR OF LONDON
Authors: Taylor Meg
Published: June 2012

From a place where you can learn about the world's first business computer, to a restaurant where you can enjoy the absolutely best lemon parfait, we have packaged an alternative business tour of London. All aboard.
THE VENTURE LAB
Authors: Dushnitsky Gary
Published: June 2012

The pharmaceutical industry is the testing ground for a major shift in how entrepreneurial companies understand and utilise different sources of venture capital. Gary Dushnitsky ventures inside the lab.
EXECUTIVE SUMMARY: FALLING OUT OF FAVOUR
Authors: Inesi M Ena , Gruenfeld Deborah H , Galinsky Adam D
Published: June 2012

M Ena Inesi, Deborah H Gruenfeld and Adam D Galinsky, ‘How power corrupts relationships: Cynical attributions for others’ generous acts', Journal of Experimental Social Psychology, 27 January 2012, http://www.sciencedirect.com/science/article/pii/s002210311200011x
EXECUTIVE SUMMARY: STRATEGIC HESITANCE
Authors: Julio Brandon , Yook Youngsuk
Published: June 2012

Brandon Julio and Youngsuk Yook, ‘Political uncertainty and corporate investment cycles’, The Journal of Finance 67, no. 1, 2012.
An observational, prospective study of monthly adalimumab therapy for disease maintenance in psoriasis patients: a possible new therapeutic option for good responders to the initial induction treatment
Authors: Taniguchi T. , Noda S. , Takahashi N. , Yoshimura H. , Mizuno K. , Adachi M.
Published: June 2012

Background  While adalimumab is a mainstay of treatment for moderate to severe chronic plaque psoriasis, the data regarding optimal treatment intervals for therapeutic maintenance are limited.

Objective  We compared the clinical efficacy of biweekly maintenance administration of adalimumab with that of monthly treatment.

Methods  17 psoriasis patients treated with adalimumab 40 mg every other week with initial loading dose of 80 mg until week 24 were assigned to the maintenance therapy with adalimumab 40 mg either every other week (n = 7), or every month (n = 10). The treatment efficacy was evaluated by the proportion of patients who achieved PASI 75 from the baseline at weeks 36, 48 and 60. There was no selection bias between the two groups.

Results  At week 24, all the patients except for one in each group achieved PASI 75. In both groups, all the patients who achieved PASI 75 at week 24 maintained PASI 75 responses at week 60. Regarding two patients who did not achieve PASI 75 at week 24, one biweekly treated patient experienced a gradual increase in therapeutic response while one monthly treated patient showed exacerbation after week 24.

Conclusion  Monthly adalimumab treatment seems to be a reasonable treatment option for patients who responded well to initial standard adalimumab treatment for 24 weeks. Since there are several limitations in this study, including the number of patients, observation period, and patients’ characteristics, large randomized controlled trials are needed to confirm these results.
The Socio‐Economic Gradient in Teenagers' Reading Skills: How Does England Compare with Other Countries?*
Authors: Jerrim John
Published: June 2012

A number of studies have explored the link between family background and children's achievement in a cross‐national context. A common finding is that there is a stronger association in England than in other parts of the developed world. Rather less attention has been paid, however, to England's comparative position at different points of the achievement distribution. Is the test score gap particularly big between the most able children from advantaged and disadvantaged homes, or are differences particularly pronounced between low achievers? This issue is investigated using the Programme for International Student Assessment (PISA) 2009 data set. The association between family background and high achievement is found to be stronger in England than in most other developed countries, and there is little evidence that this has changed over time. However, socio‐economic differences at the bottom of the achievement distribution are no more pronounced in England than elsewhere. I discuss the implications of these findings for social mobility and educational policy in the UK.
Effects of rest temperature, contact activation, and sample technique on canine thrombelastography
Authors: Ralph Alan G. , Brainard Benjamin M. , Pittman Jennifer R. , Babski Danielle M. , Koenig Amie
Published: June 2012

Objective

To determine the effects of rest temperature, contact activation (CA), and sample collection technique on thrombelastography (TEG) using canine whole blood.

Design

Prospective, experimental study.

Setting

University‐based research facility.

Animals

Twelve healthy, adult, mixed‐breed dogs.

Interventions

Blood was collected by jugular venipuncture. Tubes containing 3.2% sodium citrate, with and without 75 μg/mL corn trypsin inhibitor (CTI), were filled by vacuum. Samples rested for 30 minutes at 3 temperatures: 37°C, room temperature (RT, 20–22°C), or warmed to 37°C 5 minutes prior to analysis (prewarmed). Samples were analyzed at 37°C. CTI‐treated samples were analyzed with and without 1:50,000 tissue factor (TF) as activator. Six dogs were also tested similarly using a needle/syringe collection technique.

Measurement and Main Results

Prewarmed samples exhibited greater MA compared to RT (55.5 ± 7.2 mm vs. 53.5 ± 6.0, P< 0.05), while 37°C samples exhibited a steeper angle (56.7 ± 10.4°C vs. 52.4 ± 8.6°C) and greater MA (55.9 ± 7.5 mm vs. 53.5 ± 6.0 mm) than RT samples (both P< 0.05). CTI‐treated samples were hypocoagulable (R time 45 min [7.5–56.8 min], angle 8.2°C [5.1–42.5°C], MA 29.2 ± 9.7 mm, P< 0.001), with TF activation returning all but the angle (42.5 ± 7.6°C) to values similar to citrated samples (angle = 56.7 ± 10.4°C, P = 0.017). Collection using a syringe/needle method revealed a shorter R time for prewarmed samples only (R time 4.7 ± 0.7 min, vs. 5.6 ± 0.8 min for vacuum‐collected samples, P = 0.008).

Conclusions

Even in the absence of exogenous activators, CA has an impact on canine TEG results. The effects of rest temperatures and sample collection technique on TEG appear to be minimal.
Autologous blood transfusion following red blood cell salvage for the management of blood loss in 3 dogs with hemoperitoneum
Authors: Hirst Caroline , Adamantos Sophie
Published: June 2012

Objective

To describe the use of autologous transfusion using a red blood cell salvage device for the management of large volume hemorrhage in 3 dogs with hemoperitoneum.

Case Series Summary

Three dogs were managed for large volume hemorrhage by autologous transfusion of red blood cells after cell salvage. In all cases, blood was salvaged from the abdominal cavity during surgery. The causes of hemorrhage included testicular arterial hemorrhage after castration, hepatic parenchymal hemorrhage following hepatic dissection for intrahepatic portosystemic shunt ligation, and intra‐abdominal serosal hemorrhage associated with Angiostrongylus vasorum infection. In all cases, autologous transfusion was not associated with any identified complications and contributed to improved cardiovascular stability and packed cell volume.

New or Unique Information Provided

This case series is the first to describe the use of a semiautomated red blood cell salvage system for the clinical management of acute hemorrhage in dogs. This case series provides evidence that this procedure can be used safely and effectively for the management of clinical hemorrhage. On this basis, further veterinary evaluation can be justified.
Low tidal volume ventilation in healthy dogs
Authors: Oura Trisha , Rozanski Elizabeth A. , Buckley Gareth , Bedenice Daniela
Published: June 2012

Objective

To determine if low tidal volume (VT) ventilation is associated with the development of respiratory acidosis and changes in lung function in healthy dogs.

Design

Randomized prospective experimental cross‐over study.

Setting

Pulmonary function laboratory at a university teaching hospital.

Animals

Five healthyBeagle dogs.

Interventions

Dogs were anesthetized and randomly mechanically ventilated withVTof 6, 8, 10, 12, and 15 mL/kg while maintaining a constant minute volume.

Measurements and Main Results

Arterial blood gases and pulmonary mechanics were collected after 15 minutes of equilibration at eachVT. Repeated measuresANOVAwas used to determine the effect ofVTwith aP‐value of <0.05 considered significant, and aPearson product moment was used to determine correlation betweenVTand pHandPaCO2.VThad a significant effect onPaCO2(P< 0.001) and on pH(P< 0.001) with lowerVTbeing associated with higherPaCO2and lower pH. There was a strong correlation betweenVTandPaCO2(r= –0.87) andVTand pH(r= 0.83). Increased airway pressures and pulmonary compliance were associated with increasingVT.

Conclusions

There is a predictable decrease in the pH, decrease in airway pressure, decrease in compliance, and increase in thePaCO2associated with lowerVT. LowVTventilation is well tolerated in healthy dogs; the role of lowVTventilation in dogs with acute lung injury/acute respiratory distress syndrome as well as the influence of positive end expiratory pressure requires further evaluation.
The atypical antidepressant mianserin exhibits agonist activity at κ‐opioid receptors
Authors: Olianas Maria C , Dedoni Simona , Onali Pierluigi
Published: June 2012

BACKGROUND AND PURPOSE Antidepressants are known to interact with the opioid system through mechanisms not completely understood. We previously reported that tricyclic antidepressants act as agonists at distinct opioid receptors. Here, we investigated the effect of the atypical antidepressant mianserin at cloned and native opioid receptors.

EXPERIMENTAL APPROACH Effects of mianserin were examined in CHO cells transfected with human opioid receptors, C6 glioma cells and rat brain membranes by the use of radioligand binding and functional assays including the stimulation of [35S]GTPγS binding and MAPK phosphorylation.

KEY RESULTS Mianserin displayed 12‐ and 18‐fold higher affinity for κ‐ than µ‐ and δ‐opioid receptors respectively. In [35S]GTPγS assays, mianserin selectively activated κ‐opioid receptors. The agonist activity was antagonized by the selective κ‐opioid blocker nor‐binaltorphimine (nor‐BNI). The mianserin analogue mirtazapine also displayed κ‐opioid agonist activity. Mianserin and mirtazapine increased ERK1/2 phosphorylation in CHO cells expressing κ‐opioid receptors and C6 cells, and these effects were antagonized by nor‐BNI. In rat striatum and nucleus accumbens, mianserin stimulated [35S]GTPγS binding in a nor‐BNI‐sensitive manner with maximal effects lower than those of the full κ‐opioid agonists (–)‐U50,488 and dynorphin A. When combined, mianserin antagonized the effects of the full κ‐opioid receptor agonists in [35S]GTPγS assays and reduced the stimulation of p38 MAPK and ERK1/2 phosphorylation by dynorphin A.

CONCLUSIONS AND IMPLICATIONS In different cell systems, mianserin directly activates κ‐opioid receptors, displaying partial agonist activity at brain receptors. Thus, this property appears to be a common feature of different classes of antidepressants.