bluuebunny/crossref_metadata_2025 huggingface dataset:
Unmasking alternative splicing inside protein-coding exons defines exitrons and their role in proteome plasticity
Authors: Marquez Yamile , Höpfler Markus , Ayatollahi Zahra , Barta Andrea , Kalyna Maria
Published: May 2015

Alternative splicing (AS) diversifies transcriptomes and proteomes and is widely recognized as a key mechanism for regulating gene expression. Previously, in an analysis of intron retention events in Arabidopsis, we found unusual AS events inside annotated protein-coding exons. Here, we also identify such AS events in human and use these two sets to analyse their features, regulation, functional impact, and evolutionary origin. As these events involve introns with features of both introns and protein-coding exons, we name them exitrons (exonic introns). Though exitrons were detected as a subset of retained introns, they are clearly distinguishable, and their splicing results in transcripts with different fates. About half of the 1002 Arabidopsis and 923 human exitrons have sizes of multiples of 3 nucleotides (nt). Splicing of these exitrons results in internally deleted proteins and affects protein domains, disordered regions, and various post-translational modification sites, thus broadly impacting protein function. Exitron splicing is regulated across tissues, in response to stress and in carcinogenesis. Intriguingly, annotated intronless genes can be also alternatively spliced via exitron usage. We demonstrate that at least some exitrons originate from ancestral coding exons. Based on our findings, we propose a “splicing memory” hypothesis whereby upon intron loss imprints of former exon borders defined by vestigial splicing regulatory elements could drive the evolution of exitron splicing. Altogether, our studies show that exitron splicing is a conserved strategy for increasing proteome plasticity in plants and animals, complementing the repertoire of AS events.
Boundary conditions to the effect of fluency and comprehension on AAD when targeting Hispanics vs Whites with single meaning vs polysemous slogans
Authors: Zúñiga Miguel Angel , Torres Ivonne M. , Niculescu Mihai
Published: May 2015

Purpose

– This paper aims to show that high ethnic identifying Hispanics and Whites pursue different routes discussed in the Elaboration Likelihood Model when processing single meaning versus polysemous slogan ads. The authors found that high ethnic identifying Hispanics used the peripheral route (processing fluency) to a higher extent compared to Whites who used the central route (comprehension) to process ads.

Design/methodology/approach

– In this study, 310 undergraduate students of a Southwestern university were randomly assigned to one of two conditions (slogan: single meaning vs polysemous) in a between-subjects experimental design. Subsequently, participants responded to statements measuring constructs of interest and demographics. Participants were debriefed at the end of the survey.

Findings

– It was found that high ethnic identifying Hispanics used the peripheral route (processing fluency) to a higher extent compared to Whites who used the central route (comprehension) to process advertisements. Results suggest that while polysemous slogans are similarly interpreted by subject independent of their ethnic identification score, for single-meaning slogans, the impact of comprehension on attitudes toward the advertisement (AAD) is significantly different for low (vs high) ethnic identification individuals.

Research limitations/implications

– A future study needs to study brand attitudes and purchase intentions. Additionally, strategies in developing advertisements that influence comprehension or processing fluency need to be studied.

Practical implications

– This paper
'
s contribution to the processing fluency literature is to propose that ethnic identification and slogan meaning are variables that have great potential in influencing consumers’ perceptions about advertisements. Advertisers will have these variables to control to maximize the persuasiveness of advertisements.

Originality/value

– Minimal research focusing on polysemy in marketing exists. In advertising, comprehension is commonly studied, leaving processing fluency out. This research addresses the issue by focusing on how single-meaning and polysemous slogans are processed (via comprehension or processing fluency) by consumers and how their ethnic identification affects their AAD.
Developmental plasticity affects sexual size dimorphism in an anole lizard
Authors: Bonneaud Camille , Marnocha Erin , Herrel Anthony , Vanhooydonck Bieke , Irschick Duncan J. , Smith Thomas B.
Published: May 2015

While developmental plasticity has been shown to contribute to sexual size dimorphism (SSD) in laboratory studies, its role in shapingSSDvariation in wild vertebrate populations is unclear.

Here we use a field study and a laboratory experiment to show that resource availability influences the degree ofSSDamong insular populations ofAnolis sagreilizards in the Bahamas.

Total amounts of food biomass explained variation in male, but not female, body size on six Bahamian islands, giving rise to significant differences inSSD.

Laboratory experiments on a captive colony ofA. sagreiconfirmed that variation inSSDwas mediated by the effects of prey biomass on developmental plasticity in males, but not females. Indeed, males grew faster and attained larger sizes as adults under high‐food treatments than under restricted diets, whereas adult females retained similar body sizes under both conditions.

Our results indicate that the amount of food available can influence intersexual variation in body size within a vertebrate species. Sex‐specific developmental plasticity may be favoured if it allows individuals to take advantage of varying levels of food opportunities offered by different habitats, by reducing competition between the sexes. As such, plasticity in response to food availability may have played a role in the invasion success ofA. sagrei.

This study adds to our growing understanding of the effect of resource availability in shapingSSDin reptiles and lends further support to the condition‐dependent hypothesis, according to which the larger sex should display greater plasticity in growth in response to environmental conditions.
Human disturbance increases functional but not structural variability of stream fungal communities
Authors: Tolkkinen Mikko , Mykrä Heikki , Markkola Annamari M. , Muotka Timo
Published: May 2015

Temporal stability of ecosystem functions is often regulated by the same environmental factors that also shape diversity. Therefore, species diversity, ecosystem functions and their environmental regulators should be considered together to understand and predict the consequences of anthropogenic disturbances on ecosystems.

We studied the influence of land‐use disturbance (agriculture) and a natural stressor (low pH due to specific geology) on the temporal variability (variability among successive years) of fungal decomposer communities and leaf decomposition rates in streams. We used next‐generation sequencing techniques (pyrosequencing) to determine the composition of fungal assemblages.

Temporal variability of leaf decomposition was higher in human‐disturbed streams than in circumneutral reference or naturally acidic sites, whereas the latter two did not differ. Fungal operational taxonomic unit (OTU) richness and evenness were lower in human‐impacted sites than in circumneutral reference sites. However, there were no significant differences between stream types in the temporal variability of fungal community composition.

Fungal OTU evenness was negatively and among‐year variability of water chemistry positively related to temporal variability in leaf decomposition. Partial regressions showed that these two factors had independent effects on decomposition rates. Although the dominant OTUs in the disturbed streams were temporally stable, they did not maintain stable ecosystem functions, suggesting that variability in decomposition was driven mainly by changes in the metabolic responses of dominant taxa to environmental fluctuations.

Our results show that leaf decomposition rates in reference sites vary little through time, supporting the use of leaf decomposition assays in bioassessment. Our results also highlight the importance of measuring not only the mean rates, but also temporal variability of process rates when assessing the influence of human disturbance on ecosystem functioning.
Expression of Smad7 and Smad ubiquitin regulatory factor 2 in a rat model of chronic pancreatitis
Authors: Hou Xiao Jia , Jin Zhen Dong , Jiang Fei , Zhu Jian Wei , Li Zhao Shen
Published: May 2015

Objective

To quantify the expressions of Smad7 and Smad ubiquitin regulatory factor 2 (Smurf2) in the pancreas in rats with chronic pancreatitis (CP).

Methods

A total of 16 male Wistar rats were randomly divided into the control group and the CP group, with 8 rats in each group. CP was induced in vivo with dibutyltin dichloride (DBTC). Four weeks after DBTC administration, histological assessment and the measurement of hydroxyproline content in the pancreatic tissues were performed to assess the inflammation and fibrosis of the pancreas. Immunohistochemisty and reverse transcription polymerase chain reaction (RT‐PCR) for transforming growth factor (TGF)‐β1 and α‐smooth muscle actin (α‐SMA) were applied to assess activated pancreatic stellate cells (PSC) and TGF‐β1 expression. Smad7 and Smurf2 expressions in the pancreas were measured using Western blot and RT‐PCR.

Results

Typical histopathological characteristics of DBTC‐induced CP in the rats with extensively activated PSC. Compared with the control group, the expressions of TGF‐β1, α‐SMA and hydroxyproline content in the pancreatic tissues in the CP group were significantly increased. Meanwhile, the mRNA and protein expressions of Smad7 and Smurf2 were significant increased in the fibrotic pancreas, in which the expressions of Smad7 proteins showed an obvious reduction compared with controls.

Conclusion

The dysregulation of Smad7 and Smurf2 may be associated with the pathogenesis of pancreatic fibrosis through the TGF‐β signaling pathway.
Impaired postural stability after laparoscopic surgery
Authors: Eskildsen K. Z. , Staehr‐Rye A. K. , Rasmussen L. S. , Rosenberg J. , Claudius C. , Kjær B. H. , Clausen H. V. , Gätke M. R.
Published: May 2015

Background

Early postoperative mobilisation may reduce patient morbidity and improve hospital efficiency by accelerated discharge. The aim of this study was to measure postural stability early after laparoscopic surgery in order to assess how early it is safe to mobilise and discharge patients.

Methods

We included 25 women undergoing outpatient gynaecological laparoscopic surgery in the study. Patients received standardised anaesthesia with propofol, remifentanil and rocuronium. Postural stability was assessed preoperatively, at 30 min after tracheal extubation, and at discharge from the post‐anaesthesia care unit using a force platform where sway area, mean sway and sway velocity were determined. The assessments were done with eyes closed and with eyes open. The primary outcome was the change in sway area with eyes closed 30 min after extubation. Data are reported as median (25–75% range).

Results

Three patients could not perform all the test's 30 min after extubation.

Thirty minutes after extubation, sway area with eyes closed had increased significantly with 84 mm2 (9–172, P = 0.011) and 108 mm2 with eyes open (25–295, P = 0.0017). Median mean sway had also increased significantly 30 min postoperatively. No significant changes were found for sway velocity.

We found no significant changes in mean sway, sway area or sway velocity at discharge from the post‐anaesthesia care unit approximately 2 h after surgery.

Conclusion

Postural stability was significantly impaired 30 min after outpatient gynaecological laparoscopic surgery. However, the postural stability was normalised at discharge from the post‐anaesthesia care unit 2 h after surgery.
Examination of a Dual‐Process Model Predicting Riding with Drinking Drivers
Authors: Hultgren Brittney A. , Scaglione Nichole M. , Cleveland Michael J. , Turrisi Rob
Published: May 2015

Background

Nearly 1 in 5 of the fatalities in alcohol‐related crashes are passengers. Few studies have utilized theory to examine modifiable psychosocial predictors of individuals' tendencies to be a passenger in a vehicle operated by a driver who has consumed alcohol. This study used a prospective design to test a dual‐process model featuring reasoned and reactive psychological influences and psychosocial constructs as predictors of riding with drinking drivers (RWDD) in a sample of individuals aged 18 to 21.

Methods

College students (N = 508) completed web‐based questionnaires assessing RWDD, psychosocial constructs (attitudes, expectancies, and norms), and reasoned and reactive influences (intentions and willingness) at baseline (the middle of the spring semester) and again 1 and 6 months later. Regression was used to analyze reasoned and reactive influences as proximal predictors of RWDD at the 6‐month follow‐up. Subsequent analyses examined the relationship between the psychosocial constructs as distal predictors of RWDD and the mediation effects of reasoned and reactive influences.

Results

Both reasoned and reactive influences predicted RWDD, while only the reactive influence had a significant unique effect. Reactive influences significantly mediated the effects of peer norms, attitudes, and drinking influences on RWDD. Nearly all effects were constant across gender except parental norms (significant for females).

Conclusions

Findings highlight that the important precursors of RWDD were reactive influences, attitudes, and peer and parent norms. These findings suggest several intervention methods, specifically normative feedback interventions, parent‐based interventions, and brief motivational interviewing, may be particularly beneficial in reducing RWDD.
Neonatal vitamin A supplementation associated with increased atopy in girls
Authors: Aage S. , Kiraly N. , Da Costa K. , Byberg S. , Bjerregaard‐Andersen M. , Fisker A. B. , Aaby P. , Benn C. S.
Published: May 2015

Background

Neonatal vitamin A supplementation (NVAS) is currently being considered as policy in countries at risk of deficiency. A previous study suggested that NVAS may be associated with increased atopy. We examined the effect of NVAS on atopy by conducting long‐term follow‐up of a previous randomized controlled trial in Guinea‐Bissau.

Methods

In 2002–2004, we randomized 4345 normal birthweight neonates to NVAS (50 000 IU retinyl palmitate) or placebo together with their Bacillus Calmette–Guérin vaccination. In 2013, we visited the 1692 (39%) children now aged 8–10 years who were still living in the study area, and 1478 (87%) were found at home. Provided consent, a skin prick test was performed, and history of allergic symptoms was recorded. Associations of NVAS and atopy (defined as skin prick test reaction of ≥3 mm) were analysed using binomial regression.

Results

Of the 1430 children with a valid skin prick test, 228 (16%) were positive (more boys (20%) than girls (12%), P‐value < 0.0001). NVAS did not increase the overall risk of atopy (RR 1.10 [95% CI 0.87–1.40]). However, NVAS was associated with significantly increased risk among females (RR 1.78 [1.17–2.72]) but not among males (0.86 [0.64–1.15], P‐value for interaction between NVAS and gender = 0.005). Furthermore, NVAS was associated with increased risk of wheezing among females (RR 1.80 [1.03–3.17], but not among males, P‐value for interaction = 0.05).

Conclusion

The study corroborated previous observations; NVAS was associated with increased risk of atopy and wheezing, in this study only among females. Further studies on NVAS and atopy are warranted.
Re‐evaluation of Pre‐pump Arterial Pressure to Avoid Inadequate Dialysis and Hemolysis: Importance of Prepump Arterial Pressure Monitoring in Hemodialysis Patients
Authors: Shibata Eriko , Nagai Kojiro , Takeuchi Risa , Noda Yasuhiro , Makino Tomomi , Chikata Yusuke , Hann Michael , Yoshimoto Sakiya , Ono Hiroyuki , Ueda Sayo , Tamaki Masanori , Murakami Taichi , Matsuura Motokazu , Abe Hideharu , Doi Toshio
Published: May 2015

Prepump arterial pressure (PreAP) is monitored to avoid generating excessive negative pressure. The National Kidney Foundation K/DOQI clinical practice guidelines for vascular access recommend that PreAP should not fall below −250 mm Hg because excessive negative PreAP can lead to a decrease in the delivery of blood flow, inadequate dialysis, and hemolysis. Nonetheless, these recommendations are consistently disregarded in clinical practice and pressure sensors are often removed from the dialysis circuit. Thus far, delivered blood flow has been reported to decrease at values more negative than −150 mm Hg of PreAP. These values have been analyzed by an ultrasonic flowmeter and not directly measured. Furthermore, no known group has evaluated whether PreAP‐induced hemolysis occurs at a particular threshold. Therefore, the aim of this study was to clarify the importance of PreAP in the prediction of inadequate dialysis and hemolysis. By using different diameter needles, human blood samples from healthy volunteers were circulated in a closed dialysis circuit. The relationship between PreAP and delivered blood flow or PreAP and hemolysis was investigated. We also investigated the optimal value for PreAP using several empirical monitoring methods, such as a pressure pillow. Our investigation indicated that PreAP is a critical factor in the determination of delivered blood flow and hemolysis, both of which occured at pressure values more negative than −150 mm Hg. With the exception of direct pressure monitoring, commonly used monitoring methods for PreAP were determined to be ineffective. We propose that the use of a vacuum monitor would permit regular measurement of PreAP.
Computational Modeling of Neonatal Cardiopulmonary Bypass Hemodynamics With Full Circle of Willis Anatomy
Authors: Piskin Senol , Ündar Akif , Pekkan Kerem
Published: May 2015

Cardiopulmonary bypass (CPB) procedure is employed to repair most congenital heart defects (CHD). Cannulation is a critical component of this procedure where the location and diameter of cannula controls the hemodynamic performance. State‐of‐the‐art computational studies of neonatal CPB employed an isolated aortic arch region by truncating the three‐dimensional (3D) patient‐specific cerebral system. The present work expanded these studies where the 3D patient‐specific MRI reconstruction of the cerebral system, including the Circle of Willis (CoW), is integrated with a hypoplastic neonatal aortic arch. The inlet of the arterial cannula is assigned a steady velocity boundary condition of the CPB pump, while all outlets are modeled as resistance boundary conditions, thus allowing acute comparisons between different cannula configurations. Three‐dimensional (3D) flow simulations in the aortic arch model are performed at a Reynolds number of 2150 using an experimentally validated commercial solver. Results demonstrate that the inclusion of 3D CoW is essential to predict the accurate head‐neck blood perfusion and therefore critical in deciding the neonatal aortic cannulation strategy preoperatively. Using this integrated model two CPB configurations are studied, where the cannulas were placed at innominate artery (IA) (IA‐cannula configuration) and ductus arteriosus (DA) (DA‐cannula configuration). Configuration change produced significant differences in flow splits and local hemodynamics of blood flow throughout the whole aortic arch, neck and cerebral arteries. Percent flow rate differences between the IA‐ and DA‐cannula configurations are computed to be: 19%, for descending aorta, 198% for ascending aorta (perfusing coronary arteries), 91% for right anterior cerebral artery, and 68% for left anterior cerebral artery. Another important finding is the retrograde flow at vertebral arteries for IA‐cannula configuration, but not for DA‐cannula. These results may help to translate better neonatal arterial cannulae design for minimizing cerebral complications during CPB procedures.
Intra‐Aortic Balloon Pump Support in the Isolated Beating Porcine Heart in Nonischemic and Ischemic Pump Failure
Authors: Schampaert Stéphanie , van Nunen Lokien X. , Pijls Nico H. J. , Rutten Marcel C. M. , van Tuijl Sjoerd , van de Vosse Frans N. , van ‘t Veer Marcel
Published: May 2015

The blood pressure changes induced by the intra‐aortic balloon pump (IABP) are expected to create clinical improvement in terms of coronary perfusion and myocardial oxygen consumption. However, the measured effects reported in literature are inconsistent. The aim of this study was to investigate the influence of ischemia on IABP efficacy in healthy hearts and in shock. Twelve slaughterhouse porcine hearts (hearts 1–12) were connected to an external circulatory system, while physiologic cardiac performance was restored. Different clinical scenarios, ranging from healthy to cardiogenic shock, were simulated by step‐wise administration of negative inotropic drugs. In hearts 7–12, severe global myocardial ischemia superimposed upon the decreased contractile states was created. IABP support was applied in all hearts under all conditions. Without ischemia, the IABP induced a mild increase in coronary blood flow and cardiac output. These effects were strongly augmented in the presence of persisting ischemia, where coronary blood flow increased by 49 ± 24% (P < 0.01) and cardiac output by 17 ± 6% (P < 0.01) in case of severe pump failure. As expected, myocardial oxygen consumption increased in case of ischemia (21 ± 17%; P < 0.01), while it slightly decreased without (−3 ± 6%; P < 0.01). In case of progressive pump failure due to persistent myocardial ischemia, the IABP increased hyperemic coronary blood flow and cardiac output significantly, and reversed the progressive hemodynamic deterioration within minutes. This suggests that IABP therapy in acute myocardial infarction is most effective in patients with viable myocardium, suffering from persistent myocardial ischemia, despite adequate epicardial reperfusion.
Carbon Dioxide and Acetate‐Free Biofiltration: A Relationship to be Investigated
Authors: Marano Marco , D'Amato Anna , Patriarca Alessandro , Di Nuzzi Luigi Michele , Giordano Gelsomina , Iulianiello Giuseppe
Published: May 2015

As the name reveals, acetate‐free biofiltration (AFB) is featured by lack of acetate and this would seem to allow better hemodynamic stability. However, AFB also has a unique characteristic of carbon dioxide (CO2)‐free dialysate, whereas all other modern dialysis techniques imply an overload of CO2 from dialysate to the patient. This notwithstanding the role of CO2 in tolerance to dialysis treatment, both AFB and all other dialysis techniques seem not investigated in due depth. Specifically, the amount of CO2 coming back to the patient's bloodstream during AFB and bicarbonate dialysis (BD) is unknown. We measured partial pressure of CO2 (pCO2) in blood samples withdrawn from the venous line of the extracorporeal circuit during BD and subsequently during AFB in 22 stable chronic hemodialysis outpatients. The amount of CO2 coming back to the patient's bloodstream is higher in BD (59.1 ± 4.0 mmol/L) than in AFB (42.8 ± 4.5 mmol/L, P < 0.0001). Such difference exceeds 30%. Moreover, shifting from BD to AFB shows, notably for each patient, the reduction of pCO2 toward physiological values. BD implies CO2 overload from dialysate, whereas AFB does not. Further studies are required to evaluate if AFB would be the most appropriate dialysis technique in patients affected by chronic, but especially acute, lung diseases.
Subcutaneous immunization with a novel immunogenic candidate (urease) confers protection againstBrucella abortusandBrucella melitensisinfections
Authors: Abkar Morteza , Amani Jafar , Sahebghadam Lotfi Abbas , Nikbakht Brujeni Gholamreza , Alamian Saeed , Kamali Mehdi
Published: May 2015

Brucellosis is a world prevalent endemic illness that is transmitted from domestic animals to humans.Brucellaspp. exploits urease for survival in the harsh conditions of stomach during the gastrointestinal infection. In this study, we examined the immune response and the protection elicited by using recombinantBrucellaurease (rUrease) vaccination inBALB/c mice. Theureasegene was cloned inpET28a and the resulting recombinant protein was employed as subunit vaccine. Recombinant protein was administered subcutaneously and intraperitoneally. Dosage reduction was observed with subcutaneous (SC) vaccination when compared with intraperitoneal (IP) vaccination.rUrease induced mixed Th1–Th2 immune responses with high titers of specific IgG1 and IgG2a. In lymphocyte proliferation assay, splenocytes fromIPandSC‐vaccinated mice displayed a strong recall proliferative response with high amounts ofIL‐4,IL‐12 andIFN‐γ production. Vaccinated mice were challenged with virulentBrucella melitensis,B. abortusandB. suis. TheSCvaccination route exhibited a higher degree of protection thanIPvaccination (p value ≤ 0.05). Altogether, our results indicated thatrUrease could be a useful antigen candidate for the development of subunit vaccines against brucellosis.
Survey of farmer knowledge and attitudes to endemic disease management in South Australia, with a focus on bovine viral diarrhoea (bovine pestivirus)
Authors: Lanyon SR , Anderson ML , Reichel MP
Published: May 2015

Objective

We aimed to establish the attitudes of South Australian cattle farmers towards endemic animal disease prevention and control, with a particular focus on the awareness of and attitudes towards bovine viral diarrhoea (BVD).

Methods

This cross‐sectional postal survey involved mailing a questionnaire to all South Australian cattle owners with 35 or more head of cattle.

Results

Worms and lice were the most common animal disease concerns. Less than half of responding farmers were adequately vaccinating their herds against clostridial diseases, but 53.0% stated that they utilised quarantine procedures. Less than 20% of respondents had actively taken part in BVD educational opportunities, or had vaccinated or tested their herd for BVD; less than 20% of respondents were actively involved in any systematic control of Johne's disease. Overall, farmers’ actual knowledge of BVD was lower than their perceived understanding, although their interest in BVD and its control was high.

Conclusions

Disease prevention measures such as vaccination, quarantine and participation in systematic control schemes were used by a minority of respondents. The results suggest that respondents acknowledge BVD as an important and relevant disease, despite many believing it was not a problem in their herd. Interest in BVD appears to be high and it is likely that an education program would be well received.
Unraveling the pathogenesis of Hoyeraal–Hreidarsson syndrome, a complex telomere biology disorder
Authors: Glousker Galina , Touzot Fabien , Revy Patrick , Tzfati Yehuda , Savage Sharon A.
Published: May 2015

Hoyeraal–Hreidarsson (HH) syndrome is a multisystem genetic disorder characterized by very short telomeres and considered a clinically severe variant of dyskeratosis congenita. The main cause of mortality, usually in early childhood, is bone marrow failure. Mutations in several telomere biology genes have been reported to cause HH in about 60% of the HH patients, but the genetic defects in the rest of the patients are still unknown. Understanding the aetiology of HH and its diverse manifestations is challenging because of the complexity of telomere biology and the multiple telomeric and non‐telomeric functions played by telomere‐associated proteins in processes such as telomere replication, telomere protection, DNA damage response and ribosome and spliceosome assembly. Here we review the known clinical complications, molecular defects and germline mutations associated with HH, and elucidate possible mechanistic explanations and remaining questions in our understanding of the disease.
How I manage cerebral vasculopathy in children with sickle cell disease
Authors: Brousse Valentine , Kossorotoff Manoelle , de Montalembert Mariane
Published: May 2015

Sickle cell disease induces specific brain alterations that involve both the macrocirculation and the microcirculation. The main overt neurovascular complications in children are infarctive stroke, transient ischaemic attack and cerebral haemorrhage. Silent cerebral infarction, cognitive dysfunction and recurrent headache are also common. Cerebrovascular disease selectively affects children with the HbSS or HbS‐β0 genotypes (i.e. sickle cell anaemia). The incidence of stroke peaks between 2 and 5 years of age (1·02/100 patient‐years) and increases with the severity of the anaemia. Most strokes can be prevented by annual transcranial Doppler screening from 2 to 16 years of age and providing chronic blood transfusion when this investigation shows elevated blood‐flow velocities. The role for hydroxycarbamide in children with abnormal transcranial Doppler findings is under investigation. After a stroke, chronic blood transfusion is very strongly recommended, unless haematopoietic stem cell transplantation can be performed. Routine magnetic resonance imaging shows that more than one‐third of children have silent cerebral infarction, which is associated with cognitive impairments. Screening for silent infarcts seems legitimate, since their presence may lead to supportive treatments. The role for more aggressive interventions such as hydroxycarbamide or chronic blood transfusion is debated.
MiR‐940 inhibits hepatocellular carcinoma growth and correlates with prognosis of hepatocellular carcinoma patients
Authors: Yuan Bo , Liang Yasha , Wang Duoning , Luo Fengming
Published: May 2015

Hepatocellular carcinoma (HCC) is among the leading causes of cancer‐related death in China. Deregulation of microRNA (miRNA) contributes to HCC development by influencing cell growth, apoptosis, migration or invasion. It has been proved that miR‐940 plays important roles in various cancers. Here we investigated the role of miR‐940 in HCC. We found that miR‐940 was remarkably decreased in HCC tissues and cell lines. Importantly, lower miR‐940 expression in HCC tissues significantly correlated with the reduced patient's survival rate. Overexpression of miR‐940 inhibited HCC cell line growth and induced cell apoptosis, and vice versa. Estrogen‐related receptor gamma (ESRRG) was targeted by miR‐940, and suppression of ESRRG inhibited HCC cell lines growth and induced cell apoptosis. In conclusion, we found that a lower level of miR‐940 in HCC promoted cellular proliferation via ESRRG, which may lead to the short survival period of HCC patients.
Non‐steady‐state hematopoiesis regulated by the C/EBPβ transcription factor
Authors: Hirai Hideyo , Yokota Asumi , Tamura Akihiro , Sato Atsushi , Maekawa Taira
Published: May 2015

Steady‐state hematopoiesis responds to extracellular stimuli to meet changing demands and also to pathologically altered intracellular signaling. Granulocyte production increases following infection or in response to cytokine stimulation, and activation of the CCAAT/enhancer‐binding protein β (C/EBPβ) transcription factor is required for such stress‐induced granulopoiesis, whereas C/EBPα plays a critical role in maintaining steady‐state granulopoiesis. Different roles of these C/EBP transcription factors in different modes of hematopoiesis are evolutionally conserved from zebrafish to humans. In addition to reactions against infections, C/EBPβ is responsible for cancer‐driven myelopoiesis, which promotes cancer progression, at least in part, by abrogating the immune response in the cancer microenvironment. The BCR–ABL fusion protein activates emergency‐specific pathway of granulopoiesis by upregulating C/EBPβ. This in turn causes chronic phase chronic myeloid leukemia, which is characterized by myeloid expansion. The C/EBPβ transcription factor also plays a role in other hematological malignancies of both myeloid and lymphoid lineage origin. Thus, elucidation of the upstream and downstream networks surrounding C/EBPβ will lead to the development of novel therapeutic strategies for diseases mediated by non‐steady‐state hematopoiesis.
Nestin as a marker of cancer stem cells
Authors: Neradil Jakub , Veselska Renata
Published: May 2015

The crucial role of cancer stem cells (CSCs) in the pathology of malignant diseases has been extensively studied during the last decade. Nestin, a class VI intermediate filament protein, was originally detected in neural stem cells during development. Its expression has also been reported in different tissues under various pathological conditions. Specifically, nestin has been shown to be expressed in transformed cells of various human malignancies, and a correlation between its expression and the clinical course of some diseases has been proved. Furthermore, the coexpression of nestin with other stem cell markers was described as a CSC phenotype that was subsequently verified using tumorigenicity assays. The primary aim of this review is to summarize the recent findings regarding nestin expression in CSCs, its possible role in CSC phenotypes, particularly with respect to capacity for self‐renewal, and its utility as a putative marker of CSCs.
Attenuation of experimental asthma by mycobacterial protein combined with CpG requires a TLR9‐dependent IFN‐γ‐CCR2 signalling circuit
Authors: Prado R. Q. , Bertolini T. B. , Piñeros A. R. , Gembre A. F. , Ramos S. G. , Silva C. L. , Borges M. C. , Bonato V. L. D.
Published: May 2015

Background

Allergic asthma is a chronic pulmonary disease characterized by a Th2 inflammatory response. The modulation of a Th2 immune response based on immune deviation to a Th1 pattern or induction and migration of regulatory T cells to the lungs constitutes one of the major therapeutic approaches that is being investigated for the treatment of allergic asthma. The potentials of Mycobacterium leprae 65‐kD heat‐shock protein or Toll‐like receptor 9 ligand (CpG oligodeoxynucleotides) as immune modulators for the treatment of airway allergic disease have been studied individually.

Objective

Mycobacterial protein combined with CpG was used as immunotherapy for airway allergy.

Methods

Using an ovalbumin‐induced asthma model, mice were sensitized and challenged, and then treated with mycobacterial heat‐shock protein (Hsp65) combined with CpG.

Results

The treatment of mice with established allergy led to the attenuation of eosinophilia, Th2 cytokines and airway hyperresponsiveness. Hsp65 plus CpG treatment also induced an increase in OVA‐specific IFN‐γ levels and in the frequency of lung inflammatory monocytes. Moreover, we show that the reduction of eosinophilia and the recruitment of inflammatory monocytes to the lungs required early triggering of TLR9, IFN‐γ and CCR2 by immunotherapy components.

Conclusion

In addition to immune deviation to a Th1 response in the modulation of Th2 allergic inflammation, our findings also attribute an important role to the innate response mediated by TLR9, associated with the recruitment of CCR2‐dependent monocytes.

Clinical Relevance

Our findings show that the Hsp65/CpG treatment is a promising strategy for consideration in translational studies.
Bone density and microarchitecture in endogenous hypercortisolism
Authors: dos Santos Camila V. , Vieira Neto Leonardo , Madeira Miguel , Alves Coelho Maria Caroline , de Mendonça Laura Maria Carvalho , Paranhos‐Neto Francisco de Paula , Lima Inayá Corrêa Barbosa , Gadelha Mônica R. , Farias Maria Lucia Fleiuss
Published: May 2015

Objective

Osteoporosis is a serious and underestimated complication of endogenous hypercortisolism that results in an increased risk of fractures, even in patients with normal or slightly decreased bone mineral density (BMD). Alterations in bone microarchitecture, a very important component of bone quality, may explain bone fragility. The aim of this study was to investigate bone density and microarchitecture in a cohort of patients with endogenous Cushing's syndrome (CS).

Design

Cross‐sectional study.

Patients

Thirty patients with endogenous active CS and fifty‐one age‐, sex‐ and body mass index‐matched controls were included.

Measurements

Participants were studied for areal BMD (dual‐energy X‐ray absorptiometry) of the lumbar spine (LS), femoral neck (FN), total femur (TF) and radius (33%), and for volumetric bone density (vBMD) and structure using high‐resolution peripheral quantitative computed tomography (HR‐pQCT) of the distal radius and distal tibia.

Results

Patients with active CS exhibited lower areal BMD and Z‐score values in the LS, FN and TF (P < 0·003 for all comparisons). At HR‐pQCT, the patients with CS also had lower cortical area (P = 0·009 at the radius and P = 0·002 at the tibia), lower cortical thickness (P = 0·02 at the radius and P = 0·002 at the tibia), lower cortical density (P = 0·008 at the tibia) and lower total vBMD (P = 0·002 at the tibia). After the exclusion of hypogonadal individuals, the patients with CS maintained the same microarchitectural and densitometric alterations described above.

Conclusions

Endogenous hypercortisolism has deleterious effects on bone, especially on cortical bone microstructure. These effects seem to be a more important determinant of bone impairment than gonadal status.
Comparison of perioperative and short‐term oncological outcomes after single‐ or multiport surgery for colorectal cancer
Authors: Tei M. , Wakasugi M. , Akamatsu H.
Published: May 2015

Aim

The aim of this retrospective study was to compare the short‐term surgical results of single‐port surgery (SPS) with those of multiport surgery (MPS) for colorectal cancer.

Method

We studied 673 consecutive patients who underwent SPS or MPS for colorectal cancer in our department from January 2008 to December 2013. The operative parameters and oncological outcome were analysed and compared between the SPS and the MPS groups retrospectively.

Results

The SPS and MPS groups did not differ significantly in terms of preoperative evaluation. The median operative time was significantly shorter with SPS than with MPS (176 min vs 193 min; P < 0.001). The two groups did not differ significantly in terms of postoperative complications. Length of hospital stay was significantly shorter with SPS than with MPS (8 days vs 10 days; P < 0.001). Oncological resection was similar in the two groups. The disease‐free survival rates at 2 years according to the TNM stage did not differ significantly between the two groups (Stage I, 98.5% vs 94.7%; Stage II, 93.4% vs 90.7%; and Stage III, 70.8% vs 68.4%).

Conclusion

Our experience demonstrates that SPS is safe and can provide oncological outcomes equal to those of MPS in patients with colorectal cancer.
Infants’ grip strength predicts mu rhythm attenuation during observation of lifting actions with weighted blocks
Authors: Upshaw Michaela B. , Bernier Raphael A. , Sommerville Jessica A.
Published: May 2015

Research has established that the body is fundamentally involved in perception: bodily experience influences activation of the shared neural system underlying action perception and production during action observation, and bodily characteristics influence perception of the spatial environment. However, whether bodily characteristics influence action perception and its underlying neural system is unknown, particularly in early ontogeny. We measured grip strength in 12‐month‐old infants and investigated relations with mu rhythm attenuation, an electroencephalographic correlate of the neural system underlying action perception, during observation of lifting actions performed with differently weighted blocks. We found that infants with higher grip strength exhibited significant mu attenuation during observation of lifting actions, whereas infants with lower grip strength did not. Moreover, a progressively strong relation between grip strength and mu attenuation during observation of lifts was found with increased block weight. We propose that this relation is attributable to differences in infants’ ability to recognize the effort associated with lifting objects of different weights, as a consequence of their developing strength. Together, our results extend the body's role in perception by demonstrating that bodily characteristics influence action perception by shaping the activation of its underlying neural system.
Three‐year‐olds express suspense when an agent approaches a scene with a false belief
Authors: Moll Henrike , Kane Sarah , McGowan Luke
Published: May 2015

Research on early false belief understanding has entirely relied on affect‐neutral measures such as judgments (standard tasks), attentional allocation (looking duration, preferential looking, anticipatory looking), or active intervention. We used a novel, affective measure to test whether preschoolers affectively anticipate another's misguided acts. In two experiments, 3‐year‐olds showed more expressions of suspense (by, e.g. brow furrowing or lip biting) when they saw an agent approach a scene with a false as opposed to a true belief (Experiment 1) or ignorance (Experiment 2). This shows that the children anticipated the agent's surprise and disappointment when encountering reality. The findings suggest that early implicit knowledge of false beliefs includes anticipations of the affective implications of erring. This vital dimension of beliefs should no longer be ignored in research on early theory of mind.
Phosphorylcholine antibodies are diminished in ANCA‐associated vasculitis
Authors: Wilde Benjamin , Slot Marjan , van Paassen Pieter , Theunissen Ruud , Kemna Michael , Witzke Oliver , Cohen Tervaert Jan Willem
Published: May 2015

Background/Aim

ANCA‐associated (AAV) vasculitis is an autoimmune small‐vessel vasculitis and may be associated with accelerated atherosclerosis as suggested by current literature. Antibodies against oxidized lipoproteins (OxLDL) and phosphorylcholine (Pc) protect from atherosclerosis. This study characterizes these antibodies in AAV.

Methods

Pc‐ and anti‐OxLDL antibodies were determined in sera of 39 AAV patients and 44 healthy controls (HC). Intima‐media thickness (IMT, carotids) and pulse wave velocity (PWV, A. femoralis) were measured.

Results

Pc‐/OxLDL IgM antibodies were significantly reduced in AAV. IMT and PWV were negatively associated with anti‐Pc antibodies in HC only.

Conclusion

Atheroprotective anti‐Pc/anti‐OxLDL antibodies are significantly reduced in AAV possibly explaining accelerated atherosclerosis in vasculitis patients.
Suppressed inflammatory gene expression during human hypertrophic scar compared to normotrophic scar formation
Authors: van den Broek Lenie J. , van der Veer Willem M. , de Jong Etty H. , Gibbs Susan , Niessen Frank B.
Published: May 2015

Hypertrophic scar formation is a result of adverse cutaneous wound healing. The pathogenesis of hypertrophic scar formation is still poorly understood. A problem next to the lack of suitable animal models is that often normal skin is compared to hypertrophic scar (HTscar) and not to normotrophic scar (NTscar) tissue. Another drawback is that often only one time period after wounding is studied, while scar formation is a dynamic process over a period of several months. In this study, we compared the expression of genes involved in inflammation, angiogenesis and extracellular matrix (ECM) formation and also macrophage infiltration in biopsies obtained before and up to 52 weeks after standard surgery in five patients who developed HTscar and six patients who developed NTscar. It was found that HTscar formation coincided with a prolonged decreased expression of inflammatory genes (TNFα, IL‐1α, IL‐1RN, CCL2, CCL3, CXCL2, CXCR2, C3 and IL‐10) and an extended increased expression of ECM‐related genes (PLAU, Col3A1, TGFβ3). This coincided with a delayed but prolonged infiltration of macrophages (type 2) in HTscar tissue compared to NTscar tissue. These findings were supported by immunohistochemical localization of proteins coding for select genes named above. Our study emphasizes that human cutaneous wound healing is a dynamic process that is needed to be studied over a period of time rather than a single point of time. Taken together, our results suggest innate immune stimulatory therapies may be a better option for improving scar quality than the currently used anti‐inflammatory scar therapies.
The effect of biochar management on soil and plant community properties in a boreal forest
Authors: Gundale Michael J. , Nilsson Marie‐Charlotte , Pluchon Nathalie , Wardle David A.
Published: May 2015

Biochar management has been proposed as a possible tool to mitigate anthropogenic CO2 emissions, and thus far its impacts in forested environments remain poorly understood. We conducted a large‐scale, replicated field experiment using 0.05‐ha plots in the boreal region in northern Sweden to evaluate how soil and vegetation properties and processes responded to biochar application and the disturbance associated with burying biochar in the soil. We employed a randomized block design, where biochar and soil mixing treatments were established in factorial combination (i.e., control, soil mixing only, biochar only, and biochar and soil mixing; n = 6 plots of each). After two growing seasons, we found that biochar application enhanced net soil N mineralization rates and soil concentrations regardless of the soil mixing treatment, but had no impact on the availability of , the majority of soil microbial community parameters, or soil respiration. Meanwhile, soil mixing enhanced soil concentrations, but had negative impacts on net N mineralization rates and several soil microbial community variables. Many of the effects of soil mixing on soil nutrient and microbial community properties were less extreme when biochar was also added. Biochar addition had almost no effects on vegetation properties (except for a small reduction in species richness of the ground layer vegetation), while soil mixing caused significant reductions in graminoid and total ground layer vegetation cover, and enhanced seedling survival rates of P. sylvestris, and seed germination rates for four tree species. Our results suggest that biochar application can serve as an effective tool to store soil C in boreal forests while enhancing availability. They also suggest that biochar may serve as a useful complement to site preparation techniques that are frequently used in the boreal region, by enhancing soil fertility and reducing nutrient losses when soils are scarified during site preparation.
Are sunk costs in exporting country specific?
Authors: Moxnes Andreas
Published: May 2015

Abstract Previous studies have shown that there are significant sunk entry costs in exporting. However, the empirical literature has not addressed whether these costs are global or country specific. In this paper, I show that both are present and estimate that country‐specific costs are about three times the magnitude of global costs. Furthermore, I show that international standards harmonization has strong positive effects on imported variety in small and remote markets. Calibration of a modified Chaney (2008) model indicates that these markets will gain access to 3–4% more imported varieties when global costs increase by 10%, holding total entry costs constant.
Tax incentives in fiscal federalism: an integrated perspective
Authors: Kelders Christian , Koethenbuerger Marko
Published: May 2015

AbstractModels of fiscal federalism rarely account for the efficiency implications of intergovernmental fiscal ties for federal tax policy. This paper shows that fiscal institutions such that federal tax deductibility, vertical revenue‐sharing, and fiscal equalization (being common features of existing federations) encourage local taxation, but may discourage federal taxation. Furthermore, the structure of public spending is skewed towards local spending. We also show that, when considering Leviathan governments, fiscal institutions reduce confiscatory taxation by the federal government. The result is contrary to the Cartelization Hypothesis (Brennan and Buchanan 1980). Finally, we characterize the efficient design of intergovernmental fiscal ties.