bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alteration of Tight Junction Gene Expression in Celiac Disease
Authors: Jauregi‐Miguel Amaia , Fernandez‐Jimenez Nora , Irastorza Iñaki , Plaza‐Izurieta Leticia , Vitoria Juan Carlos , Bilbao Jose Ramon 
Published: February 2014

ABSTRACTObjective:The aim of the present study was to characterize the deregulation of epithelial tight junction genes and investigate its reversibility on removal of dietary gluten in small intestinal mucosa in celiac disease (CD).Methods:The expression levels of 23 genes related to tight junctions were studied in biopsies from 16 patients with active CD and compared with biopsies from the same patients taken after 2 years on gluten‐free diet (GFD) and with 16 non‐CD controls.Results:Nine genes showed altered expression levels in patients with active disease (CLDN2, PARD6A, ZAK, SYMPK, MYH14, and ACTB were upregulated, whereas MAGI1, TJP1, and PPP2R3A were downregulated). Alterations were reversible after 2 years on treatment, except for PPP2R3A, implicated in the negative control of cell growth and division. At the biological network level, important dysfunctions in several processes within the pathway were observed, including intestinal permeability, apicobasal polarity, and cell proliferation.Conclusions:Our work confirms the involvement of tight junction genes related to permeability, polarity, and cell proliferation in the epithelial destruction observed in CD. Coexpression patterns of several genes support the idea of a common regulatory mechanism that seems to be altered in active CD. In general, GFD normalization confirms the reversibility of the process, except for the constitutive downregulation of PPP2R3A suggestive of a genetic implication. Further studies in proteins and cells or tissues are necessary to confirm these findings.
Cocaine induces DNA damage in distinct brain areas of female rats under different hormonal conditions
Authors: de Souza Marilise F , Gonçales Tierre A , Steinmetz Aline , Moura Dinara J , Saffi Jenifer , Gomez Rosane , Barros Helena MT 
Published: February 2014

SummaryWe evaluated levels of neuronal DNA damage after acute or repeated cocaine treatment in different brain areas of female rats after ovariectomy or sham surgery. Rats in the control and acute groups were given saline i.p., whereas in the repeated group were given 15 mg/kg, i.p., cocaine for 8 days. After a 10 day washout period, the control group was given saline i.p., whereas rats in the acute and repeated groups were given a challenge dose of 15 mg/kg, i.p., cocaine. After behavioural assessment, rats were killed and the cerebellum, hippocampus, hypothalamus, prefrontal cortex and striatum were dissected for the Comet assay. Acute cocaine exposure induced DNA damage in all brain areas. This effect persisted after repeated administration, except in the hypothalamus, where repeated treatment did not cause increased DNA damage. Sexual hormones exhibited a neuroprotective effect, decreasing cocaine‐induced DNA damage in cycling rats in all brain areas.
ATP‐binding cassette transporter A1 (ABCA1) promotes arsenic tolerance in human cells by reducing cellular arsenic accumulation
Authors: Tan Xiaohua , Yang Li , Xian Lingling , Huang Jin , Di Chunhong , Gu Wenyi , Guo Shuli , Yang Lei 
Published: February 2014

Summary

Arsenic is a toxic element widely distributed in nature, such as water and soil. To survive this metalloid in the environment, nearly all organisms develop strategies to tolerate arsenic toxicity to some degree. Some arsenic‐resistance genes have been identified in bacteria and yeast, but for mammals, especially humans, these genes are largely unknown.

The aim of the present study was to identify these genes and benefit our intervention of arsenic resistance. We first established a human arsenic‐resistant ECV‐304 (AsRE) cell line and then used suppression subtractive hybridization and microarray analysis to identify arsenic‐resistant genes in these cells. Of the significantly upregulated genes, three ATP‐binding cassette (ABC) subfamily members, namely ABCA1, ABCE1 and ABCF1, were chosen for further study with RNA interference and overexpression analyses. The 3‐(4,5‐dimethyl‐2 thiazoyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide assay was used to determine the cell survival rate and the IC50, whereas atomic fluorescence spectrophotometry was used to determine intracellular arsenic levels.

We found that among the three ABC genes, only when ABCA1 gene expression was silenced did cells obviously lose their arsenic tolerance. The arsenic accumulation in ABCA1 deficiency AsRE cells was greater than that in wild type AsRE cells. Overexpression of ABCA1 in HeLa cells decreased arsenic accumulation in the cells and the cells were more resistant to As(III) than control cells transfected with empty vector.

These results suggest a new functional role for ABCA1 in the development of arsenic resistance in human cells.
Environmental Kuznets Curve: Conclusive Econometric Evidence for CO2
Authors: Chow Gregory C. , Li Jie 
Published: February 2014

AbstractThis paper begins with a statistical formulation of the Environmental Kuznets Curve (EKC) and discusses the major econometric problems raised in the literature in testing this hypothesis using panel data. A simple t‐test is then presented that avoids these econometric problems. The result from applying the t‐test confirms conclusively the EKC for CO2 as formulated.
China's Capital Controls: Through the Prism of Covered Interest Differentials
Authors: Cheung Yin‐Wong , Herrala Risto 
Published: February 2014

AbstractWe study the renminbi covered interest differential, an indicator of the effectiveness of capital controls. It is found that the differential is not shrinking over time and, in fact, appears larger after the global financial crisis than before. That is, capital controls in China are still substantial and effective. In addition to exchange rate changes and volatilities, the renminbi covered interest differential is affected by credit market tightness indicators. The marginal explanatory power of these macroeconomic factors, however, is small relative to the autoregressive component and the dummy variables that capture changes in China's policy.
Continuous infusion of local anaesthetic following laparoscopic hysterectomy—a randomised controlled trial
Authors: Andrews V , Wright JT , Zakaria F , Banerjee S , Ballard K 
Published: February 2014

ObjectiveTo estimate whether a continuous infusion of intraperitoneal local anaesthetic for 48 hours following laparoscopic hysterectomy reduced the need for opioids delivered with a patient‐controlled analgesia pump.DesignDouble‐blind randomised placebo‐controlled trial.SettingDistrict general hospital in the UK.PopulationWomen undergoing a laparoscopic hysterectomy for a benign indication.MethodsWomen were randomised to receive either 0.5% levobupivicaine or 0.9% normal saline via an ON‐Q elastomeric pump for 48 hours postoperatively. The amount of opioids used via the patient‐controlled analgesia pump was recorded and pain was measured using an 11‐point Box Scale.Main outcome measuresThe primary outcome was the amount of patient‐administered morphine used over the first 48 postoperative hours. Secondary outcomes were length of hospital stay, oral analgesia use and level of patient‐reported pain.ResultsSixty women participated and completed the trial. There was no difference (P = 0.59) in the median amount of patient‐administered morphine used between the levobupivicaine (23 mg) and placebo (18.5 mg) groups; median group difference 3.0 (95% CI −7.0 to 14.0). There was also no difference in the length of hospital stay with 40% of the treatment group remaining in hospital >48 hours compared with 30% of the placebo group (P = 0.08). Pain scores at all postoperative time points remained similar, with a median group difference in pain scores of 1.0 (95% CI −1.0 to 2.0) at the end of the first postoperative day.ConclusionsContinuous infusion of 0.5% levobupivicaine into the peritoneal cavity following laparoscopic hysterectomy does not have any opioid‐sparing effects.
The relationship between postpartum levator ani muscle avulsion and signs and symptoms of pelvic floor dysfunction
Authors: van Delft K , Sultan AH , Thakar R , Schwertner‐Tiepelmann N , Kluivers K 
Published: February 2014

ObjectiveTo establish the relationship between postpartum levator ani muscle (LAM) avulsion and signs and/or symptoms of pelvic floor dysfunction (PFD).DesignObservational longitudinal cohort study.SettingDistrict General University Hospital, UK.Population or samplePrimigravida at 36 weeks' gestation and 3 months postpartum.MethodsPelvic floor muscle strength (PFMS) and pelvic organ prolapse were assessed clinically using validated methods. Transperineal ultrasound was performed to identify LAM avulsion and measure hiatus dimensions. Validated questionnaires evaluated sexual function, urinary and faecal incontinence.Main outcome measuresPFD signs and symptoms related to LAM avulsion.ResultsTwo hundred and sixty nine primigravida without LAM avulsion participated and 71% (n = 191) returned postpartum. LAM avulsion was found in 21% of vaginal deliveries (n = 30, 95%CI 15.1–28.4%). Women with minor and major avulsion had worse PFMS (P < 0.038) and more anterior compartment prolapse (maximum stage 2; P < 0.024). Antenatal hiatus antero‐posterior diameter on ultrasound was significantly smaller in women sustaining avulsion (P = 0.011). Postnatal measurements were significantly increased following avulsion. Women with major avulsion were less sexually active at both antenatal and postnatal periods (P < 0.030). These women had more postnatal urinary incontinence and symptoms such as reduced vaginal sensation and ‘too loose vagina’. No postnatal differences were found for faecal incontinence, prolapse symptoms or quality of life. The correlation of differences in variables was only slight–fair with avulsion severity.ConclusionsTwenty one percent of women sustain LAM avulsion during their first vaginal delivery with significant impact on signs and symptoms of PFD. As avulsion has been described as the missing link in the development of prolapse; longer term follow‐up is vital.
Disease spectrum in patients with elevated serum tryptase levels
Authors: Aberer Elisabeth , Savic Sandra , Bretterklieber Agnes , Reiter Harald , Berghold Andrea , Aberer Werner 
Published: February 2014

AbstractBackgroundElevated serum tryptase levels can be a sign of mastocytosis, which is a rare disease associated with systemic and/or skin manifestations.ObjectiveTo investigate patients with elevated tryptase levels in regard to their underlying diseases, and to determine whether increased tryptase can be used as a diagnostic marker for underlying mastocytosis.MethodsIn a retrospective study the data of 96 patients with serum tryptase levels higher than 15 μg/L were systematically analysed. In 48 patients control investigations for baseline tryptase were performed.ResultsFifty‐three of the 96 patients had tryptase levels ≥20 μg/L. A mere 16% of the 96 patients suffered from mastocytosis and had the highest tryptase levels (P < 0.001). The remaining patients had anaphylaxis (36%), urticaria and angioedema (26%), local reactions to insect bites (4%), drug reactions (3%), or miscellaneous diagnoses (15%). Only 16 of these had acute symptoms at tryptase investigation. In all, 48 patients had a follow up; in 7/48 patients with acute symptoms normal tryptase levels were seen at control investigations, but 41/48 (85%) patients showed continuously elevated tryptase levels >15 μg/L and in 30 patients (62%) even values >20 μg/L; 11 of these patients had anaphylaxis, five urticaria, five other diagnoses and nine patients mastocytosis.ConclusionMore than 50% of patients with non‐mastocytosis such as urticaria and angioedema, drug or anaphylactic reactions repeatedly had tryptase levels higher than 20 μg/L. Since baseline tryptase >20 μg/L is a minor criterion for mastocytosis, these patients should be inspected for skin lesions of mastocytosis and receive a diagnostic body work‐up for systemic mastocytosis including a bone marrow biopsy.
Ethical Considerations for Outcome‐adaptive Trial Designs: A Clinical Researcher's Perspective
Authors: Saxman Scott Brian 
Published: February 2014

AbstractIn a typical comparative clinical trial the randomization scheme is fixed at the beginning of the study, and maintained throughout the course of the trial. A number of researchers have championed a randomized trial design referred to as ‘outcome‐adaptive randomization.’ In this type of trial, the likelihood of a patient being enrolled to a particular arm of the study increases or decreases as preliminary information becomes available suggesting that treatment may be superior or inferior. While the design merits of outcome‐adaptive trials have been debated, little attention has been paid to significant ethical concerns that arise in the conduct of such studies. These include loss of equipoise, lack of processes for adequate informed consent, and inequalities inherent in the research design which could lead to perceptions of injustice that may have negative implications for patients and the research enterprise. This article examines the ethical difficulties inherent in outcome‐adaptive trials.
Activation states of blood eosinophils in asthma
Authors: Johansson M. W. 
Published: February 2014

SummaryAsthma is characterized by airway inflammation rich in eosinophils. Airway eosinophilia is associated with exacerbations and has been suggested to play a role in airway remodelling. Recruitment of eosinophils from the circulation requires that blood eosinophils become activated, leading to their arrest on the endothelium and extravasation. Circulating eosinophils can be envisioned as potentially being in different activation states, including non‐activated, pre‐activated or ‘primed’, or fully activated. In addition, the circulation can potentially be deficient of pre‐activated or activated eosinophils, because such cells have marginated on activated endothelium or extravasated into the tissue. A number of eosinophil surface proteins, including CD69, L‐selectin, intercellular adhesion molecule‐1 (ICAM‐1, CD54), CD44, P‐selectin glycoprotein ligand‐1 (PSGL‐1, CD162), cytokine receptors, Fc receptors, integrins including αM integrin (CD11b), and activated conformations of Fc receptors and integrins, have been proposed to report cell activation. Variation in eosinophil activation states may be associated with asthma activity. Eosinophil surface proteins proposed to be activation markers, with a particular focus on integrins, and evidence for associations between activation states of blood eosinophils and features of asthma are reviewed here. Partial activation of β1 and β2 integrins on blood eosinophils, reported by monoclonal antibodies (mAbs) N29 and KIM‐127, is associated with impaired pulmonary function and airway eosinophilia, respectively, in non‐severe asthma. The association with lung function does not occur in severe asthma, presumably due to greater eosinophil extravasation, specifically of activated or pre‐activated cells, in severe disease.
Impacts of Paternal Care and Seasonal Change on Offspring Survival: A Multiseason Experimental Study of a Caribbean Frog
Authors: Lehtinen Richard M. , Green Sara E. , Pringle Jessica L. 
Published: February 2014

AbstractParental care is widespread among animals and many studies have investigated how environmental conditions influence parental care strategies. However, few studies have coupled observations of the frequency and form of parental care with manipulative studies on the function of care across multiple seasons. To address this gap, we made field observations and conducted male removal experiments in a glass frog with paternal egg attendance from the island of Tobago, West Indies. To test the hypothesis that seasonality impacts the frequency, form, and function of parental care, field observations and male removal experiments were undertaken three times, twice during the rainy season, and once in the dry season. We found seasonal differences in the frequency of egg attendance with males increasing the frequency of this behavior in the dry season, likely in response to a greater risk of clutch desiccation. We also found that clutches in which the male was removed had strongly reduced survivorship compared with controls and this pattern did not change seasonally. However, sources of mortality were strongly influenced by season. Arthropod predation was the primary source of mortality during the wet season, but in the dry season, desiccation was more important. Together, these results suggest that seasonal variation is both impacting care function as well as shaping the form that parental care takes.
Immunology of infective preterm delivery in the mare
Authors: Lyle S. K. 
Published: February 2014

SummaryPlacentitis is reported to be the cause of 9.8–33.5% of abortions, stillbirths and perinatal losses in horses. Bacterial infections are responsible for 53% of placentitis cases withStreptococcus equissp.zooepidemicusbeing isolated in 28% of these cases. Clinically, mares may have a vaginal discharge, show udder development, lactate prenatally and deliver a premature or dead foal. Major aspects of the pathogenesis of infectious preterm delivery that may require more effective therapeutic targeting are myometrial contraction, immunological aspects of preterm delivery, and the effects of proinflammatory cytokine signalling on activation of the fetal hypothalamic–pituitary–adrenal axis. This article focuses on current knowledge of inflammatory signalling secondary to equine placentitis, and the interplay among inflammation, loss of myometrial quiescence and activation of the fetal hypothalamic–pituitary–adrenal axis.
The “Quiet Migration”: Is Intercountry Adoption a Successful Intervention In the Lives of Vulnerable Children?
Authors: Misca Gabriela 
Published: February 2014

Over the past decades international adoption has become a global phenomenon involving cross‐border movement of vulnerable children, mainly from poor, undeveloped countries to wealthier countries. Debates around international adoptions invoke often‐passionate arguments for and against. At times seen as the ultimate form of imperialism, trafficking and exploitation of children, international adoptions are also praised as successful interventions in the lives of the most vulnerable children worldwide. This article draws on research findings on the outcomes of international adoption and its impact on various aspects of adopted children's development and identifies the gaps relating to evidence‐based interventions best suited to the needs of these children postinternational adoption.KeypointsBased on the reviewed research findings, this paper supports the following arguments:

overall, children adopted internationally can and do thrive in their adoptive countries;
such success is guaranteed by the high commitment of adoptive parents and the availability of post‐adoption support services;
there is, however, a lack of evidence‐based practice relating to interventions best suited to the needs of these children post‐international adoption;
following a globally standardised process and strict protocols may help alleviate illicit activity in international adoptions;
existing guidelines must be tightened to ensure that children are the central focus in intercountry adoption and that their development is not affected by cross‐border movement.
Structural and redox properties of the small laccase Ssl1 from Streptomyces sviceus
Authors: Gunne Matthias , Höppner Astrid , Hagedoorn Peter‐Leon , Urlacher Vlada B. 
Published: February 2014

Laccases (EC 1.10.3.2) are members of the multicopper oxidase family. They oxidize diverse electron‐rich substrates through electron abstraction by the type 1 copper ion in the enzyme active site. Abstracted electrons are transferred to the trinuclear copper cluster, where molecular oxygen serves as final acceptor and is reduced to water. Laccase activity is assumed to depend on the redox potential of its type 1 copper ion. Whereas numerous studies have been undertaken to elucidate the determinants of the redox potential of type 1 copper ions in one‐domain cupredoxins and in three‐domain laccases, such experimental investigations are lacking for recently described, small, two‐domain laccases. In this work, the crystal structure of the small laccase Ssl1 from Streptomyces sviceus was solved, and the positions that might influence the redox potential of Ssl1 were depicted. On the basis of this knowledge, several Ssl1 variants were constructed with an increase in redox potential of 16–81 mV, from 375 mV to 391–456 mV. Mutation of residues in close proximity to the type 1 copper center resulted in a predicted increase in the redox potential of the copper center; however, there was a reduced specific activity for the oxidation of 2,6‐dimethoxyphenol, which has a relatively low redox potential. Mutations more distant to the type 1 copper also led to an increased redox potential of the copper center, and resulted in variants able to oxidize the high redox potential substrates 1,2‐dihydroxyanthraquinone‐3‐sulfonic acid (Alizarin Red S) and indigo carmine more efficiently than wild‐type Ssl1.DatabaseThe atomic coordinates of the structure of Ssl1 laccase from Streptomyces sviceus and structure factors have been deposited in the RCSB Protein Data Bank (4M3H)Structured digital abstract•Ssl1 and Ssl1 bind by x-ray crystallography (View interaction)
High‐severity fire corroborated in historical dry forests of the western United States: response to Fulé et al.
Authors: Williams Mark A. , Baker William L. 
Published: February 2014

AbstractAccurate assessment of changing fire regimes is important, since climatic change and people may be promoting more wildfires. Government wildland fire policies and restoration programmes in dry western US forests are based on the hypothesis that high‐severity fire was rare in historical fire regimes, modern fire severity is unnaturally high and restoration efforts should focus primarily on thinning forests to eliminate high‐severity fire. Using General Land Office (GLO) survey data over large dry‐forest landscapes, we showed that the proportion of historical forest affected by high‐severity fire was not insignificant, fire severity has not increased as a proportion of total fire area and large areas of dense forest were present historically (Williams & Baker, Global Ecology and Biogeography, 21, 1042–1052, 2012; W&B). In response, Fulé et al. (Global Ecology and Biogeography, 2013, doi: 10.1111/geb.12136; FE) suggest that our inferences are unsupported and land management based on our research could be damaging to native ecosystems. Here, we show that the concerns of FE are unfounded. Their criticism comes from misquoting W&B, mistaking W&B's methods, misusing evidence (e.g. from Aldo Leopold) and missing substantial available evidence. We also update corroboration for the extensive historical high‐severity fire shown by W&B. We suggest that restoration programmes are misdirected in seeking to reduce all high‐severity fire in dry forests, given findings from spatially extensive GLO data and other sources.