bluuebunny/crossref_metadata_2025 huggingface dataset:
Trapped in desert springs: phylogeography of Australian desert spring snails
Authors: Murphy Nicholas P. , Breed Martin F. , Guzik Michelle T. , Cooper Steven J. B. , Austin Andrew D.
Published: June 2012

Aim  We investigate the phylogeographical history and determine the time‐scale of population divergence of hydrobiid freshwater snails (genus Trochidrobia) inhabiting groundwater springs in the Australian desert. We test the hypothesis that divergence between geographically distinct snail populations occurred simultaneously due to their isolation in hydrologically discrete spring systems, i.e. ‘trapped in desert springs’.

Location  Groundwater springs of the Great Artesian Basin (GAB) in central Australia.

Methods  DNA sequence data from the mitochondrial cytochrome c oxidase subunit I gene and the nuclear 28S and internal transcribed spacer rRNA genes were used to reconstruct phylogenetic relationships within and among three species of Trochidrobia (Hydrobiidae): T. punicea (13 spring groups, n = 90), T. smithi (12 spring groups, n = 62) and T. minuta (2 spring groups, n = 4). Bayesian relaxed molecular clock analyses and approximate Bayesian computation were used to date lineage divergence and distinguish between alternative biogeographical scenarios.

Results  The diversification of the three Trochidrobia species probably occurred between 2.54 and 9.3 Ma, prior to the formation of the springs c. 1 Ma. Intraspecific divergences within the two widespread species occurred after the formation and colonization of the springs. Coalescent modelling and molecular clock analyses supported a simultaneous radiation of five allopatric intraspecific snail lineages within T. punicea (two lineages) and T. smithi (three lineages) across the GAB springs examined.

Main conclusions  The analyses support the ‘trapped in desert springs’ hypothesis for the diversification of intraspecific lineages within the species T. punicea and T. smithi. This hypothesis suggests that the formation of deserts around Lake Eyre in the early Pleistocene led to the hydrological isolation of spring complexes in the GAB, resulting in significant molecular divergence, but no morphological divergence, of Trochidrobia snail populations.
Habitat distribution models for intertidal seaweeds: responses to climatic and non‐climatic drivers
Authors: Martínez Brezo , Viejo Rosa M. , Carreño Francisco , Aranda Silvia C.
Published: June 2012

Aim  Because intertidal organisms often live close to their physiological tolerance limits, they are potentially sensitive indicators of climate‐driven changes in the environment. The goals of this study were to assess the effect of climatic and non‐climatic factors on the geographical distribution of intertidal macroalgae, and to predict future distributions under different climate‐warming scenarios.

Location  North‐western Iberian Peninsula, southern Europe.

Methods  We developed distribution models for six ecologically important intertidal seaweed species. Occurrence and microhabitat data were sampled at 1‐km2 resolution and analysed with climate variables measured at larger spatial scales. We used generalized linear models and applied the deviance and Bayesian information criterion to model the relationship between environmental variables and the distribution of each target species. We also used hierarchical partitioning (HP) to identify predictor variables with higher independent explanatory power.

Results  The distributions of Himanthalia elongata and Bifurcaria bifurcata were correlated with measures of terrestrial and marine climate, although in opposite directions. Model projections under two warming scenarios indicated the extinction of the former at a faster rate in the Cantabrian Sea (northern Spain) than in the Atlantic (west). In contrast, these models predicted an increase in the occurrence of B. bifurcata in both areas. The occurrences of Ascophyllum nodosum and Pelvetia canaliculata, species showing rather static historical distributions, were related to specific non‐climatic environmental conditions and locations, such as the location of sheltered sites. At the southernmost distributional limit, these habitats may present favourable microclimatic conditions or provide refuges from competitors or natural enemies. Model performances for Fucus vesiculosus and F. serratus were similar and poor, but several climatic variables influenced the occurrence of the latter in the HP analyses.

Main conclusions  The correlation between species distributions and climate was evident for two species, whereas the distributions of the others were associated with non‐climatic predictors. We hypothesize that the distribution of F. serratus responds to diverse combinations of factors in different sections of the north‐west Iberian Peninsula. Our study shows how the response of species distributions to climatic and non‐climatic variables may be complex and vary geographically. Our analyses also highlight the difficulty of making predictions based solely on variation in climatic factors measured at coarse spatial scales.
Development of a quantitative real‐time PCR for the detection of Tenacibaculum maritimum and its application to field samples
Authors: Fringuelli E , Savage P D , Gordon A , Baxter E J , Rodger H D , Graham D A
Published: June 2012

The development and the application of a quantitative real‐time PCR for the detection of Tenacibaculum maritimum are described. A set of primers and probe was designed to amplify a 155‐bp fragment specific to the T. maritimum 16S rRNA gene. The test was shown to be very sensitive, able to detect as little as 4.8 DNA copies number μL−1. In addition, the assay was found to have a high degree of repeatability and reproducibility, with a linear dynamic range (R2 = 0.999) extending over 6 log10 dilutions and a high efficiency (100%). The assay was applied to DNA samples extracted from 48 formalin‐fixed paraffin‐embedded (FFPE) Atlantic salmon, Salmo salar, gill tissues showing varying degrees of gill pathology (scored 0–3) and from 26 jellyfish samples belonging to the species Phialella quadrata and Muggiaea atlantica. For each sample, the bacterial load was normalised against the level of the salmonid elongation factor alpha 1 (ELF) detected by a second real‐time PCR using previously published primers and probe. Tenacibaculum maritimum DNA was detected in 89% of the blocks with no signs of gill disease as well as in 95% of the blocks with mild‐to‐severe gill pathology. Association between bacterial load and gill pathology severity was investigated. T. maritimum DNA was detected at low level in four of the 26 jellyfish tested.
Enhancement of Hsp70 synthesis protects common carp, Cyprinus carpio L., against lethal ammonia toxicity
Authors: Sung Y Y , Roberts R J , Bossier P
Published: June 2012

Exposure to TEX‐OE®, a patented extract of the prickly pear cactus (Opuntia ficus indica) containing chaperone‐stimulating factor, was shown to protect common carp, Cyprinus carpio L., fingerlings against acute ammonia stress. Survival was enhanced twofold from 50% to 95% after exposure to 5.92 mg L−1 NH3, a level determined in the ammonia challenge bioassay as the 1‐h LD50 concentration for this species. Survival of TEX‐OE®‐pre‐exposed fish was enhanced by 20% over non‐exposed controls during lethal ammonia challenge (14.21 mg L−1 NH3). Increase in the levels of gill and muscle Hsp70 was evident in TEX‐OE®‐pre‐exposed fish but not in the unexposed controls, indicating that application of TEX‐OE® accelerated carp endogenous Hsp70 synthesis during ammonia perturbation. Protection against ammonia was correlated with Hsp70 accretion.
Paternity assignment and demographic closure in the New Zealand southern right whale
Authors: CARROLL EMMA L. , CHILDERHOUSE SIMON J. , CHRISTIE MARK , LAVERY SHANE , PATENAUDE NATHALIE , ALEXANDER ALANA , CONSTANTINE ROCHELLE , STEEL DEBBIE , BOREN LAURA , SCOTT BAKER C.
Published: June 2012

The identification and characterization of reproductively isolated subpopulations or ‘stocks’ are essential for effective conservation and management decisions. This can be difficult in vagile marine species like marine mammals. We used paternity assignment and ‘gametic recapture’ to examine the reproductive autonomy of southern right whales (Eubalaena australis) on their New Zealand (NZ) calving grounds. We derived DNA profiles for 34 mother–calf pairs from skin biopsy samples, using sex‐specific markers, 13 microsatellite loci and mtDNA haplotypes. We constructed DNA profiles for 314 adult males, representing 30% of the census male abundance of the NZ stock, previously estimated from genotypic mark‐recapture modelling to be 1085 (95% CL 855, 1416). Under the hypothesis of demographic closure and the assumption of equal reproductive success among males, we predict: (i) the proportion of paternities assigned will reflect the proportion of the male population sampled and (ii) the gametic mark–recapture (GMR) estimate of male abundance will be equivalent to the census male estimate for the NZ stock. Consistent with these predictions, we found that the proportion of assigned paternities equalled the proportion of the census male population size sampled. Using the sample of males as the initial capture, and paternity assignment as the recapture, the GMR estimate of male abundance was 1001 (95% CL 542, 1469), similar to the male census estimate. These findings suggest that right whales returning to the NZ calving ground are reproductively autonomous on a generational timescale, as well as isolated by maternal fidelity on an evolutionary timescale, from others in the Indo‐Pacific region.
n‐Butyrate Anergized Effector CD4+ T Cells Independent of Regulatory T cell Generation or Activity
Authors: Fontenelle B. , Gilbert K. M.
Published: June 2012

CD4+ T cell anergy reflects the inability of CD4+ T cells to respond functionally to antigenic stimulation through proliferation or IL‐2 secretion. Histone deacetylase (HDAC) inhibitors have been shown to induce anergy in antigen‐activated CD4+ T cells. However, questions remain if HDAC inhibitors mediate anergy through direct action upon activated CD4+ T cells or through the generation and/or enhancement of regulatory T (Treg) cells. To assess if HDAC inhibitor n‐butyrate induces anergy independent of the generation or expansion of FoxP3+ Treg cells in vitro, we examine n‐butyrate‐treated murine CD4+ T cells for anergy induction and FoxP3+ Treg activity. Whereas n‐butyrate decreases CD4+ T cell proliferation and IL‐2 secretion, n‐butyrate did not augment FoxP3 protein production or confer a suppressive phenotype upon CD4+ T cells. Collectively, these data suggest that HDAC inhibitors can facilitate CD4+ T cell functional unresponsiveness directly and independently of Treg cell involvement.
The natural history of a genetic subtype of arrhythmogenic right ventricular cardiomyopathy caused by a p.S358L mutation in TMEM43
Authors: Hodgkinson KA , Connors SP , Merner N , Haywood A , Young T‐L , McKenna WJ , Gallagher B , Curtis F , Bassett AS , Parfrey PS
Published: June 2012

To determine the phenotype and natural history of a founder genetic subtype of autosomal dominant arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by a p.S358L mutation in TMEM43. The age of onset of cardiac symptoms, clinical events and test abnormalities were studied in 412 subjects (258 affected and 154 unaffected), all of which occurred in affected males significantly earlier and more often than unaffected males. Affected males were hospitalized four times more often than affected females (p ≤ 0.0001) and died younger (p ≤ 0.001). The temporal sequence from symptoms onset to death was prolonged in affected females by 1–2 decades. The most prevalent electrocardiogram (ECG) manifestation was poor R wave progression (PRWP), with affected males twice as likely to develop PRWP as affected females (p ≤ 0.05). Left ventricular enlargement (LVE) occurred in 43% of affected subjects, with 11% fulfilling criteria for dilated cardiomyopathy. Ventricular ectopy on Holter monitor was common and occurred early: the most diagnostically useful clinical test. No symptom or test could rule out diagnosis. This ARVC subtype is a sex‐influenced lethal arrhythmogenic cardiomyopathy, with a unique ECG finding, LV dilatation, heart failure and early death, where molecular pre‐symptomatic diagnosis has the greatest clinical utility.
Association of Clostridium difficile infection with outcomes of hospitalized solid organ transplant recipients: results from the 2009 Nationwide Inpatient Sample database
Authors: Pant C. , Anderson M.P. , O'Connor J.A. , Marshall C.M. , Deshpande A. , Sferra T.J.
Published: June 2012

Background

Diarrhea is a frequent and potentially severe complication in solid organ transplant (SOT) recipients. One of the most common infectious etiologies of diarrhea in these patients is
Clostridium difficile. Our objective was to investigate the association of
C. difficile infection (CDI) with the outcomes of hospitalized SOT patients.

Methods

We extracted all adult cases with discharge diagnoses of SOT or CDI from the United States Nationwide Inpatient Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality 2009 database. We collected outcome variables (mortality, length of hospital stay [LOS], hospitalization charges, complications of the transplanted organ, and colectomy), demographic information, and comorbidity data for each of the cases. The data were evaluated using univariate and multiple variable regression analyses.

Results

We identified 49,198 cases with SOT of which 2.7% had CDI. Univariate comparisons of cases with SOT + CDI to those with SOT‐only revealed significant differences in the evaluated outcomes including in‐hospital mortality (7.4% vs. 2.4%, P < 0.001), LOS (median 9 days vs. 4 days, P < 0.001), charges (median $53,808 vs. $31,488, P < 0.001), organ complications (38.1% vs. 33.9%, P < 0.001), and colectomy (1.1% vs. 0.3%, P < 0.001). Using multiple variable regression analyses, in the SOT cohort (SOT‐only and SOT + CDI), CDI was independently associated with greater mortality (adjusted odds ratio [aOR] 2.48, 95% confidence interval [CI] = 2.22, 2.76, P < 0.001), longer LOS (difference 9.6 days, 95% CI = 9.3, 9.9, P < 0.001), higher charges (difference $69,647, 95% CI = $66,190, $73,104, P < 0.001), more complications of the transplanted organ (aOR 1.36, 95% CI = 1.28, 1.44, P < 0.001), and increased need for colectomy (aOR 3.10, 95% CI = 2.35, 4.08, P < 0.001).

Conclusions

Our results demonstrate that CDI is associated with overall significantly worse outcomes in hospitalized patients with SOT.
Respiratory support during the influenza A (H1N1) pandemic flu in Sweden
Authors: BRINK M. , HAGBERG L. , LARSSON A. , GEDEBORG R.
Published: June 2012

Background

Acute respiratory insufficiency characterised critically ill patients during the influenza A (H1N1) pandemic 2009–2010. Detailed understanding of disease progression and outcome in relation to different respiratory support strategies is important.

Methods

Data collected between August 2009 and February 2010 for a national intensive care unit influenza registry were combined with cases identified by the Swedish Institute for Infectious Disease Control.

Results

Clinical data was available for 95% (126/136) of the critically ill cases of influenza. Median age was 44 years, and major co‐morbidities were present in 41%. Respiratory support strategies were studied among the 110 adult patients. Supplementary oxygen was sufficient in 15% (16), non‐invasive ventilation (NIV) only was used in 20% (22), while transition from NIV to invasive ventilation (IV) was seen in 41% (45). IV was initiated directly in 24% (26). Patients initially treated with NIV had a higher arterial partial pressure of oxygen/fraction of oxygen in inspired gas ratio compared with those primarily treated with IV. Major baseline characteristics and 28‐day mortality were similar, but 90‐day mortality was higher in patients initially treated with NIV 17/67 (25%) as compared with patients primarily treated with IV 3/26 (12%), relative risk 1.2 (95% confidence interval 0.3–4.0).

Conclusions

Critical illness because of 2009 influenza A (H1N1) in Sweden was dominated by hypoxic respiratory failure. The majority of patients in need of respiratory support were initially treated with NIV. In spite of less severe initial hypoxemia, initiation of ventilatory support with NIV was not associated with improved outcome.
Seed Rot, a New Disease of Beech Tree Caused by Neonectria ramulariae (anamorph: Cylindrocarpon obtusiusculum)
Authors: Hirooka Yuuri , Ichihara Yu , Masuya Hayato , Kubono Takanori
Published: June 2012

During a survey of seed diseases of Fagus crenata, a new fungal disease of the seeds was found with high frequency in Akita, northern Japan. Main symptoms are often expressed as browning of the cracked parts from exposed cotyledons and complete loss of viability of infected seeds. Reddish perithecia and whitish yellow sporodochia were occasionally observed symptoms and determined that they were anamorph–telemorph relationship on the basis of both cultural observations. Inoculation studies confirmed that this fungus was the cause of seed rot. The fungus is morphologically identical with Neonectria ramulariae (anamorph: Cylindrocarpon obtusiusculum) that is well known as the soil‐born fungi around the world. Sequences between the authentic isolate of Neo. ramulariae (CBS 151.29) and the pathogenic fungus based on ITS, LSU and tub showed high similarity. Thus, ‘seed rot’, the new disease of beech seeds caused by Neo. ramulariae (anamorph: Cyl. obtusiusculum) was proposed in this study.
Timing and cell dose determine therapeutic effects of bone marrow stromal cell transplantation in rat model of cerebral infarct
Authors: Kawabori Masahito , Kuroda Satoshi , Ito Masaki , Shichinohe Hideo , Houkin Kiyohiro , Kuge Yuji , Tamaki Nagara
Published: June 2012

Stereotactic transplantation of bone marrow stromal cells (BMSCs) enables efficient delivery to the infarct brain. This study was aimed to assess its optimal timing and cell dose for ischemic stroke. The BMSCs were harvested from the green fluorescent protein‐transgenic rats and were labeled with quantum dots. The BMSCs (1 × 105 or 1 × 106) were stereotactically transplanted into the ipsilateral striatum of the rats subjected to permanent middle cerebral artery occlusion at 1 or 4 weeks post‐ischemia. Motor function was serially assessed. Using in vivo near infrared (NIR) fluorescence imaging, the engrafted BMSCs were visualized at 3 weeks post‐transplantation. Immunohistochemistry was performed to evaluate their fate. Functional recovery was significantly enhanced when both low and high doses of BMSCs were transplanted at 1 week post‐ischemia, but such therapeutic effects were observed only when the high‐dose BMSCs were transplanted at 4 weeks post‐ischemia. Both optical imaging and immunohistochemistry revealed their better engraftment in the peri‐infarct area when the high‐dose BMSCs were transplanted at 1 or 4 weeks post‐ischemia. These findings strongly suggest the importance of timing and cell dose to yield therapeutic effects of BMSC transplantation for ischemic stroke. Earlier transplantation requires a smaller number of donor cells for beneficial effects.
Hyperglycaemia, inflammation, RAS activation: Three culprits to blame for acute kidney injury emerging in healthy rats during general anaesthesia
Authors: EFRATI SHAI , BERMAN SYLVIA , ABU HAMAD RAMZIA , EL NAKIB RANIN , CHANIMOV MICHAEL , SIMAN‐TOV YARIV , WEISSGARTEN JOSHUA
Published: June 2012

Aim:  Major surgery under general anaesthesia might evoke acute kidney injury (AKI), sometimes culminating in end stage renal disease. We investigated the roles of hyperglycaemia, inflammation and renin‐angiotensin system (RAS) activation in induction of AKI following anaesthesia by different anaesthetic drugs and/or regimens.

Methods:  Ninety‐four Sprague‐Dawley rats underwent 1 h‐anaesthesia by various protocols, including repeated blood glucose and insulin measurements. Blood samples and kidneys were allocated at sacrifice, for evaluation of renal function, inflammatory status and Angiotensin‐II availability.

Results:  Hyperglycaemia emerged in unconscious rats irrespective of anaesthetic drug choice or anaesthesia regimen. Insulin increase correlated with hyperglycaemia levels. Levels of Cystatin‐C, as well as serum and urine neutrophil gelatinase‐associated lipocain (NGAL), were significantly augmented. Serum transforming growth factor beta (TGF‐β) and interleukins (IL)‐1β, ‐4, ‐6, and ‐10 were significantly increased. Intra‐renal Angiotensin‐II, TGF‐β, IL‐6 and‐10 were significantly increased. IL‐1 was decreased. IL‐4 remained unaltered.

Conclusions:  Acute hyperglycaemia, systemic and intra‐renal inflammation and RAS activation were independently triggered by induction of anaesthesia. Each confounder aggravated the impacts of the others, bringing about concomitant deterioration of renal function. Increased insulin secretion attenuated but did not abolish hyperglycaemia. Systemic inflammation was counterforced by anti‐inflammatory cytokines, whereas intra‐renal inflammation persisted, so that AKI progressed unopposed.
Experience of socioeconomic‐related inequality in dental care utilization among Thai elderly under universal coverage
Authors: Somkotra Tewarit
Published: June 2012

Aim:  To assess the socioeconomic‐related inequality in dental care utilization among Thai elderly and to determine factors associated with the observed inequality after the country achieved universal coverage.

Methods:  The data were taken from the nationally representative Thailand Health & Welfare Survey 2007. Data of 10 096 Thai elderly (aged over 60 years) were selected. Descriptive analyses of the features of dental care utilization among Thai elderly were carried out, in addition to the concentration index (Cindex) being used to quantify the extent of socioeconomic‐related inequality in dental care utilization. Logistic regression was used to determine factors associated with inequality in dental care.

Results:  Socioeconomic‐related inequality in dental care utilization among Thai elderly was shown. Also, utilization was more concentrated among wealthier older adults, as shown by the positive value of Cindex (equals 0.244). The poor elderly, however, were more likely to utilize dental care at public facilities, particularly primary care facilities. Multivariate analysis showed that certain demographic, socioeconomic and geographic characteristics were particularly associated with poor–rich differences in dental care utilization among Thai elderly.

Conclusions:  Although socioeconomic‐related inequality in dental care utilization among Thai elderly exists, the pro‐poor utilization at public facilities, particularly primary care facilities, substantiates the concerted effort to reducing inequality in dental care utilization for Thai elderly. Geriatr Gerontol Int 2013; 13: 298–306.
Laparoscopic versus open inguinal hernia repair in octogenarians: A follow‐up study
Authors: Dallas Kai B , Froylich Dvir , Choi Jacqueline J , Rosa Jonatan Hernandez , Lo Christopher , Colon Modesto J , Telem Dana A , Divino Celia M
Published: June 2012

Aim:  The elderly population is the fastest growing demographic in developed countries. It is thus imperative to assess common medical procedures in this age group. Inguinal hernia repair is a commonly carried out operation in the USA with two methods of repair existing – laparoscopic and open. Although the advantages of laparoscopic inguinal hernia repair in the general population have been shown, its role in the elderly has yet to be elucidated.

Methods:  A retrospective medical record review with prospective follow up of 115 patients aged over 80 years who underwent either open or laparoscopic inguinal hernia repair was carried out. Outcome measures included postoperative pain score, recovery time, chronic pain, wound infection, urinary retention, urinary tract infection, hematoma and recurrence. Patient satisfaction was measured with the Likert score.

Results:  Of the 115 repairs, 31 repairs were carried out laparoscopically and 84 open. Mean patient age was 83.3 years (range 80–95 years), with no difference in demographics or comorbidities between the two groups. Mean recovery time was significantly shorter in the laparoscopic group (7.5 vs 23.1 days, P = 0.02), as was the mean duration of pain in the laparoscopic group (1.4 vs 9.6 days, P = 0.04). There were no significant differences in other outcomes. There was a trend towards increased patient satisfaction in the laparoscopic group (P = 0.10).

Conclusion:  In octogenarians, laparoscopic inguinal hernia repair confers a significantly shorter duration of pain and recovery time as compared with open inguinal hernia repair, with no increase in complications. For elderly patients, laparoscopy is a viable alternative to open repair. Geriatr Gerontol Int 2013; 13: 329–333.
Multi‐scale experimental study on fatigue damage behaviour and its effect on structural nonlinear response
Authors: HE D. D. , LI Z. X. , SHENG H. Q. , CHEN C.
Published: June 2012

Experimental analyses on the structural response caused by local fatigue damage accumulation in welded details are accomplished to perform failure process and nonlinear effect analysis at different structural levels. The experiment is carried out by using welded compact tension (CT) specimens and a scaled truss specimen, and all of them have a notch at the weld toe to facilitate damage initiation. Cyclic loads are applied to those specimens to generate accumulative fatigue damage, respectively. The process of fatigue accumulation including initiation and propagation of fatigue cracks in the welded detail and resultant structural responses of CT specimens and the truss are measured with integration of multiple testing techniques. Multi‐scale experimental results show that microscopic‐/mesoscopic‐concentrated strain and extension of plastic zone in the vicinity of notch tip are both affected significantly by the fatigue damage accumulation and present appreciable nonlinear behaviour; however, the macroscopic response such as the frequency and stiffness parameters of the welded truss specimen are less sensitive to the low‐level fatigue damage. It is concluded that the fatigue failure of the welded truss is a multi‐scale progressive process due to fatigue damage trans‐scale evolving, in which the local meso‐damage firstly affects local strain of plastic zone in the vicinity of the notch tip, and then fatigue damage evolving from meso‐ to macro‐scale affects nonlinear responses of the damaged components; lastly, the fatigue failure could be expected as the results of the propagation of macroscopic fatigue cracks.
Digital image correlation measurement of near‐tip fatigue crack displacement fields: constant amplitude loading and load history effects
Authors: NOWELL D. , KARTAL M. E. , DE MATOS P. F. P.
Published: June 2012

Recent work by de Matos and colleagues employed digital image correlation to measure near tip displacement fields for fatigue cracks in 6082 T6 aluminium alloy. The main focus of this work was to directly measure fatigue crack closure, but the measurements can also be used to examine conditions at and ahead of the crack tip. In this paper, the results are re‐analysed and compared to two crack‐tip deformation models. The first assumes simple elastic deformation (according the Westergaard solution). This allows the history of crack‐tip stress intensity to be examined. Reasonable agreement with the elastic model is obtained, although there is a residual stress intensity caused by the plastic wake, which gives rise to crack closure. The second model examined is a simple elastic–plastic assumption, proposed by Pommier and colleagues. This can be applied to constant amplitude loading, although the results obtained here are very similar to the elastic case. A slightly more complex load case (a single overload in an otherwise constant amplitude variation of load) gives a much more complicated crack‐tip history. Here, the importance of crack‐tip plastic displacement, represented by the second term in Pommier's model becomes much clearer. Load history effects are captured by the residual value of this term and its associated displacement fields as well as by stress intensity factor. The implications for further modelling and experimental work are discussed.
Increased population growth rate in invasive polyploid Centaurea stoebe in a common garden
Authors: Hahn Min A. , Buckley Yvonne M. , Müller‐Schärer Heinz
Published: June 2012

Biological invasions are inherently demographic processes, but trait differences between native and introduced genotypes are rarely linked to population growth rates. Native European Centaurea stoebe occurs as two cytotypes with different life histories (monocarpic diploids, polycarpic tetraploids); however, only tetraploids have been found in its introduced range in North America. In a common garden experiment using artificial populations, we compared the demographic performance of the three geo‐cytotypes in the presence and absence of a specialist herbivore using periodic matrix models. We found no difference in population growth rate between the two European cytotypes and no significant effects of herbivory in all geo‐cytotypes. However, there was a pronounced increase in population growth rate for North American compared with European tetraploids due to increased seed production and juvenile establishment. These results suggest that genetic drift or rapid evolution, rather than pre‐adaptation through polyploidy may explain the invasion success of tetraploids.
Intensive agriculture erodes β‐diversity at large scales
Authors: Karp Daniel S. , Rominger Andrew J. , Zook Jim , Ranganathan Jai , Ehrlich Paul R. , Daily Gretchen C.
Published: June 2012

Biodiversity is declining from unprecedented land conversions that replace diverse, low‐intensity agriculture with vast expanses under homogeneous, intensive production. Despite documented losses of species richness, consequences for β‐diversity, changes in community composition between sites, are largely unknown, especially in the tropics. Using a 10‐year data set on Costa Rican birds, we find that low‐intensity agriculture sustained β‐diversity across large scales on a par with forest. In high‐intensity agriculture, low local (α) diversity inflated β‐diversity as a statistical artefact. Therefore, at small spatial scales, intensive agriculture appeared to retain β‐diversity. Unlike in forest or low‐intensity systems, however, high‐intensity agriculture also homogenised vegetation structure over large distances, thereby decoupling the fundamental ecological pattern of bird communities changing with geographical distance. This ~40% decline in species turnover indicates a significant decline in β‐diversity at large spatial scales. These findings point the way towards multi‐functional agricultural systems that maintain agricultural productivity while simultaneously conserving biodiversity.
Bile salts induce long polar fimbriae expression favouring Crohn's disease‐associated adherent‐invasive Escherichia coli interaction with Peyer's patches
Authors: Chassaing Benoit , Etienne‐Mesmin Lucie , Bonnet Richard , Darfeuille‐Michaud Arlette
Published: June 2012

Ileal lesions of patients with Crohn's disease are colonized by adherent‐invasive Escherichia coli (AIEC). The earliest lesions of recurrent Crohn's disease are erosions of Peyer's patches (PP). We recently reported the presence of a functional lpf operon in AIEC, encoding long polar fimbriae (LPF), that allows AIEC bacteria to interact with PP and to translocate across M cells. The aim of this study was to analyse the effect of gastrointestinal conditions on LPF expression in AIEC strains. The LF82 bacterial growth in an acid pH medium or at high osmolarity medium had no effect on lpf transcription level, in contrast to bacterial growth in the presence of bile salts, which promoted activation of lpf transcription. When cultured in the presence of bile salt, LF82 wild‐type bacteria, but not the isogenic mutant deleted for lpfA, exhibited a higher level of interaction with PP and a higher level of translocation through M cell monolayers. The FhlA transcriptional factor was found to be a key bacterial regulator at the origin of LPF expression in the presence of bile salts.
Tuber‐specific silencing of asparagine synthetase‐1 reduces the acrylamide‐forming potential of potatoes grown in the field without affecting tuber shape and yield
Authors: Chawla Rekha , Shakya Roshani , Rommens Caius M.
Published: June 2012

Simultaneous silencing of asparagine synthetase (Ast)‐1 and ‐2 limits asparagine (ASN) formation and, consequently, reduces the acrylamide‐forming potential of tubers. The phenotype of silenced lines appears normal in the greenhouse, but field‐grown tubers are small and cracked. Assessing the effects of silencing StAst1 and StAst2 individually, we found that yield drag was mainly linked to down‐regulation of StAst2. Interestingly, tubers from untransformed scions grafted onto intragenic StAst1/2‐silenced rootstock contained almost the same low ASN levels as those in the original silenced lines, indicating that ASN is mainly formed in tubers rather than being transported from leaves. This conclusion was further supported by the finding that overexpression of StAst2 caused ASN to accumulate in leaves but not tubers. Thus, ASN does not appear to be the main form of organic nitrogen transported from leaves to tubers. Because reduced ASN levels coincided with increased levels of glutamine, it appears likely that this alternative amide amino acid is mobilized to tubers, where it is converted into ASN by StAst1. Indeed, tuber‐specific silencing of StAst1, but not of StAst2, was sufficient to substantially lower ASN formation in tubers. Extensive field studies demonstrated that the reduced acrylamide‐forming potential achieved by tuber‐specific StAst1 silencing did not affect the yield or quality of field‐harvested tubers.
Antibodies to heteromeric glycolipid complexes in multifocal motor neuropathy
Authors: Galban‐Horcajo F. , Fitzpatrick A. M. , Hutton A. J. , Dunn S. M. , Kalna G. , Brennan K. M. , Rinaldi S. , Yu R. K. , Goodyear C. S , Willison H. J.
Published: June 2012

Background

Measurement of anti‐GM1 IgM antibodies in multifocal motor neuropathy (MMN) sera is confounded by relatively low sensitivity that limits clinical usefulness. Combinatorial assay methods, in which antibodies react to heteromeric complexes of two or more glycolipids, are being increasingly applied to this area of diagnostic testing.

Methods

A newly developed combinatorial glycoarray able to identify antibodies to 45 different heteromeric glycolipid complexes and their 10 individual glycolipid components was applied to a randomly selected population of 33 MMN cases and 57 normal or disease controls. Comparison with an enzyme‐linked immunosorbent assay (ELISA) was conducted for selected single glycolipids and their complexes.

Results

By ELISA, 22/33 MMN cases had detectable anti‐GM1 IgM antibodies, whereas 19/33 MMN samples were positive for anti‐GM1 antibodies by glycoarray. Analysis of variance (anova) revealed that of the 55 possible single glycolipids and their 1:1 complexes, antibodies to the GM1:galactocerebroside (GM1:GalC) complex were most significantly associated with MMN, returning 33/33 MMN samples as positive by glycoarray and 29/33 positive by ELISA. Regression analysis revealed a high correlation in absolute values between ELISA and glycoarray. Receiver operator characteristic analysis revealed insignificantly different diagnostic performance between the two methods. However, the glycoarray appeared to offer slightly improved sensitivity by identifying antibodies in four ELISA‐negative samples.

Conclusions

The use of combinatorial glycoarray or ELISA increased the diagnostic sensitivity of anti‐glycolipid antibody testing in this cohort of MMN cases, without significantly affecting specificity, and may be a useful assay modification for routine clinical screening.
Performance Measurement and Incentive Plans
Authors: KAUHANEN ANTTI , NAPARI SAMI
Published: June 2012

This paper explores performance measurement in incentive plans. On the basis of theory, we argue that differences in the nature of jobs between blue‐ and white‐collar employees lead to differences in incentive systems. We find that performance measurement for white‐collar workers is broader in terms of the performance measures, the organizational level of performance measurement, and the time horizon. The intensity of incentives is also stronger for white‐collar employees. All of these findings are consistent with theory.
Mental health difficulties among young people on the autistic spectrum in mainstream secondary schools: a comparative study
Authors: Hebron Judith , Humphrey Neil
Published: June 2012

Young people on the autistic spectrum (AS) may be at an increased risk of developing mental health difficulties, but to date research evidence has been equivocal and/or inadequate. The aim of the current study was to document the mental health profiles of adolescents on the AS, and to identify factors that contribute to difficulties in this area. Mental health profiles of a group of adolescents on the AS (N = 22) were compared with age, gender and special educational needs (SEN)‐provision‐matched control groups of adolescents with dyslexia (N = 21) and with no SEN (N = 23) using the Beck Youth Inventories. Additionally, five participants on the AS participated in semi‐structured interviews about their experience of school. Quantitative analysis demonstrated that adolescents on the AS experienced significantly greater anxiety, depression, anger and lower self‐concept than those with no SEN. They also experienced significantly greater anxiety and anger than those with dyslexia. Qualitative analysis revealed that problems in social relationships, understanding the nature of the AS and disruptions to routine were common contributory factors to the mental health difficulties of participants. However, interview data also revealed key coping strategies implemented by participants to help them overcome their difficulties. The implications of these findings are discussed, and methodological limitations are noted.
Homosexuality, Religion, and Science: Moral Authority and the Persistence of Negative Attitudes*
Authors: Whitehead Andrew L. , Baker Joseph O.
Published: June 2012

The liberalization of attitudes toward homosexuality in the United States over the past 30 years is well documented. Despite these changes, substantial resistance to equality for gay men and lesbians remains. Previous studies indicate that beliefs about the etiology of homosexuality are central to this discussion. Those who believe homosexuality is innate are more favorable, while those who believe it is the result of a choice are more negative. Moreover, experimental research indicates that those with negative views actually become more opposed when a natural explanation is proposed. This study highlights the importance of perceived sources of epistemic and moral authority for understanding views of homosexuality. Using stances on culturally controversial issues involving “science and religion” as indicators of where individuals place authority, we outline the connection between perceptions of moral authority and attributions about homosexuality. Analyses of a national survey of American adults show that, net of controls, one’s stance on moral authority is the strongest predictor of attributions about whether homosexuality is chosen or innate.
Cumulative and Relative Disadvantage as Long‐Term Determinants of Negative Self‐feelings*
Authors: Pals Heili , Kaplan Howard B.
Published: June 2012

We analyze the long‐term effects of neighborhood poverty and crime on negative self‐feelings of young adults. Cumulative and relative disadvantage explanations are tested with the interactive effect of (1) neighborhood and individual‐level economic disadvantage and (2) neighborhood crime and economic disadvantage. Results from a longitudinal study following adolescents to young adulthood show that the development of negative self‐feelings (a combination of depression, anxiety, and self‐derogation) is determined by relative, rather than cumulative disadvantage. The poor in affluent neighborhoods have the highest negative self‐feelings, while the relatively wealthy in poor neighborhoods have the lowest negative self‐feelings. Similarly, we find the highest increase in negative self‐feelings is found in an affluent neighborhood with crime and not in a poor neighborhood with crime.
Deciphering µ‐opioid receptor phosphorylation and dephosphorylation in HEK293 cells
Authors: Doll Christian , Pöll Florian , Peuker Kenneth , Loktev Anastasia , Glück Laura , Schulz Stefan
Published: June 2012

BACKGROUND AND PURPOSE The molecular basis of agonist‐selective signalling at the µ‐opioid receptor is poorly understood. We have recently shown that full agonists such as [D‐Ala2‐MePhe4‐Gly‐ol]enkephalin (DAMGO) stimulate the phosphorylation of a number of carboxyl‐terminal phosphate acceptor sites including threonine 370 (Thr370) and serine 375 (Ser375), and that is followed by a robust receptor internalization. In contrast, morphine promotes a selective phosphorylation of Ser375 without causing rapid receptor internalization.

EXPERIMENTAL APPROACH Here, we identify kinases and phosphatases that mediate agonist‐dependent phosphorylation and dephosphorylation of the µ‐opioid receptor using a combination of phosphosite‐specific antibodies and siRNA knock‐down screening in HEK293 cells.

KEY RESULTS We found that DAMGO‐driven phosphorylation of Thr370 and Ser375 was preferentially catalysed by G‐protein‐coupled receptor kinases (GRKs) 2 and 3, whereas morphine‐driven Ser375 phosphorylation was preferentially catalysed by GRK5. On the functional level, inhibition of GRK expression resulted in enhanced µ‐opioid receptor signalling and reduced receptor internalization. Analysis of GRK5‐deficient mice revealed that GRK5 selectively contributes to morphine‐induced Ser375 phosphorylation in brain tissue. We also identified protein phosphatase 1γ as a µ‐opioid receptor phosphatase that catalysed Thr370 and Ser375 dephosphorylation at or near the plasma membrane within minutes after agonist removal, which in turn facilitates receptor recycling.

CONCLUSIONS AND IMPLICATIONS Together, the morphine‐activated µ‐opioid receptor is a good substrate for phosphorylation by GRK5 but a poor substrate for GRK2/3. GRK5 phosphorylates µ‐opioid receptors selectively on Ser375, which is not sufficient to drive significant receptor internalization.
Allosteric nature of P2X receptor activation probed by photoaffinity labelling
Authors: Bhargava Y , Rettinger J , Mourot A
Published: June 2012

BACKGROUND AND PURPOSE In P2X receptors, agonist binding at the interface between neighbouring subunits is efficiently transduced to ion channel gating. However, the relationship between binding and gating is difficult to study because agonists continuously bind and unbind. Here, we covalently incorporated agonists in the binding pocket of P2X receptors and examined how binding site occupancy affects the ability of the channel to gate.

EXPERIMENTAL APPROACH We used a strategy for tethering agonists to their ATP‐binding pocket, while simultaneously probing ion channel gating using electrophysiology. The agonist 2′,3′‐O‐(4‐benzoylbenzoyl)‐ATP (BzATP), a photoaffinity analogue of ATP, enabled us to trap rat homomeric P2X2 receptor and a P2X2/1 receptor chimera in different agonist‐bound states. UV light was used to control the degree of covalent occupancy of the receptors.

KEY RESULTS Irradiation of the P2X2/1 receptor chimera – BzATP complex resulted in a persistent current that lasted even after extensive washout, consistent with photochemical tethering of the agonist BzATP and trapping of the receptors in an open state. Partial labelling with BzATP primed subsequent agonist binding and modulated gating efficiency for both full and partial agonists.

CONCLUSIONS AND IMPLICATIONS Our photolabelling strategy provides new molecular insights into the activation mechanism of the P2X receptor. We show here that priming with full agonist molecules leads to an increase in gating efficiency after subsequent agonist binding.
Treatment‐Resistant Medication Overuse Headache Can Be Cured
Authors: Munksgaard Signe B. , Bendtsen Lars , Jensen Rigmor H.
Published: June 2012

Objective.— To evaluate the long‐term efficacy of a structured, multidisciplinary treatment program in patients who had been treated unsuccessfully for medication overuse headache by specialists in an open‐label design.

Background.— Medication overuse headache is a common and disabling disease. Management is complicated by substantial treatment failure and relapse, and those who relapse and nonresponders to treatment are often excluded from studies on medication overuse headache.

Methods.— Patients with medication overuse headache who had previously been unsuccessfully treated by specialists and referred to a specialized, tertiary headache centre were recruited. They underwent a structured 2‐month detoxification program and were subsequently closely followed up for 10 months by a multidisciplinary team of physicians, nurses, physiotherapists, and psychologists.

Results.— Eighty‐six of 98 patients completed the study.

Primary Outcome.— At 12‐month follow‐up, headache frequency was reduced by 39.3% (P < .001), 71 patients (82.6%) remained cured of medication overuse, reduction in headache frequency of more than 50% occurred in 42 patients (48.8%), and 52 (60.5%) reverted to episodic headache. Both of these figures had increased significantly from month 2 to month 12 (P < .001). Medication use was reduced by 62.8% (P < .001).

Conclusion.— Patients with medication overuse headache previously regarded treatment‐resistant benefit considerably from multidisciplinary treatment in a structured detoxification program with close follow‐up.