bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic comparison of RNA-Seq normalization methods using measurement error models
Authors: Sun Zhaonan , Zhu Yu 
Published: August 2012

Abstract
Motivation: Further advancement of RNA-Seq technology and its application call for the development of effective normalization methods for RNA-Seq data. Currently, different normalization methods are compared and validated by their correlations with a certain gold standard. Gene expression measurements generated by a different technology or platform such as Real-time reverse transcription polymerase chain reaction (qRT–PCR) or Microarray are usually used as the gold standard. Although the current approach is intuitive and easy to implement, it becomes statistically inadequate when the gold standard is also subject to measurement error (ME). Furthermore, the current approach is not informative, because the correlation of a normalization method with a certain gold standard does not provide much information about the exact quality of the normalized RNA-Seq measurements.
Results: We propose to use the system of ME models based on qRT–PCR, Microarray and RNA-Seq gene expression data to compare and validate RNA-Seq normalization methods. This approach does not assume the existence of a gold standard. The performance of a normalization method can be characterized by a group of parameters of the system, which are referred to as the performance parameters, and these performance parameters can be consistently estimated. Different normalization methods can thus be compared by comparing their corresponding estimated performance parameters. We applied the proposed approach to compare five existing RNA-Seq normalization methods using the gene expression data of two RNA samples from the microArray Quality Control and Sequencing Quality Control projects and gained much insight about the pros and cons of these methods.
Contact: sunz@purdue.edu; yuzhu@purdue.edu
SimRare: a program to generate and analyze sequence-based data for association studies of quantitative and qualitative traits
Authors: Li Biao , Wang Gao , Leal Suzanne M. 
Published: August 2012

Abstract
Motivation: Currently, there is great interest in detecting complex trait rare variant associations using next-generation sequence data. On a monthly basis, new rare variant association methods are published. It is difficult to evaluate these methods because there is no standard to generate data and often comparisons are biased. In order to fairly compare rare variant association methods, it is necessary to generate data using realistic population demographic and phenotypic models.
Result: SimRare is an interactive program that integrates generation of rare variant genotype/phenotype data and evaluation of association methods using a unified platform. Variant data are generated for gene regions using forward-time simulation that incorporates realistic population demographic and evolutionary scenarios. Phenotype data can be obtained for both case–control and quantitative traits. SimRare has a user-friendly interface that allows for easy entry of genetic and phenotypic parameters. Novel rare variant association methods implemented in R can also be imported into SimRare, to evaluate their performance and compare results, e.g. power and Type I error, with other currently available methods both numerically and graphically.
Availability: http://code.google.com/p/simrare/
Contact: sleal@bcm.edu
An empirical Bayes mixture model for SNP detection in pooled sequencing data
Authors: Zhou Baiyu 
Published: August 2012

AbstractMotivation: Detecting single-nucleotide polymorphism (SNP) in pooled sequencing data is more challenging than in individual sequencing because of sampling variations across pools. To effectively differentiate SNP signal from sequencing error, appropriate estimation of the sequencing error is necessary. In this article, we propose an empirical Bayes mixture (EBM) model for SNP detection and allele frequency estimation in pooled sequencing data.Results: The proposed model reliably learns the error distribution by pooling information across pools and genomic positions. In addition, the proposed EBM model builds in characteristics unique to the pooled sequencing data, boosting the sensitivity of SNP detection. For large-scale inference in SNP detection, the EBM model provides a flexible and robust way for estimation and control of local false discovery rate. We demonstrate the performance of the proposed method through simulation studies and real data application.Availability: Implementation of this method is available at https://sites.google.com/site/zhouby98Contact: baiyu.zhou@einstein.yu.edu
A Bifunctional Enzyme That Has Both Monoacylglycerol Acyltransferase and Acyl Hydrolase Activities
Authors: Vijayaraj Panneerselvam , Jashal Charnitkaur B. , Vijayakumar Anitha , Rani Sapa Hima , Venkata Rao D.K. , Rajasekharan Ram 
Published: August 2012

Abstract
Monoacylglycerol acyltransferase (MGAT) catalyzes the synthesis of diacylglycerol, the precursor of triacylglycerol biosynthesis and an important signaling molecule. Here, we describe the isolation and characterization of the peanut (Arachis hypogaea) MGAT gene. The soluble enzyme utilizes invariant histidine-62 and aspartate-67 residues of the acyltransferase motif for its MGAT activity. A sequence analysis revealed the presence of a hydrolase (GXSXG) motif, and enzyme assays revealed the presence of monoacylglycerol (MAG) and lysophosphatidylcholine (LPC) hydrolytic activities, indicating the bifunctional nature of the enzyme. The overexpression of the MGAT gene in yeast (Saccharomyces cerevisiae) caused an increase in triacylglycerol accumulation. Similar to the peanut MGAT, the Arabidopsis (Arabidopsis thaliana) homolog (At1g52760) also exhibited both acyltransferase and hydrolase activities. Interestingly, the yeast homolog lacks the conserved HX4D motif, and it is deficient in the acyltransferase function but exhibits MAG and LPC hydrolase activities. This study demonstrates the presence of a soluble MGAT/hydrolase in plants. The predicted three-dimensional homology modeling and substrate docking suggested the presence of two separate substrate (MAG and LPC)-binding sites in a single polypeptide. Our study describes a soluble bifunctional enzyme that has both MGAT and hydrolase functions.
Occupational disability in bipolar disorder: analysis of predictors of being on severe disablement benefit (PREBIS study data)
Authors: Grande I. , Goikolea J. M. , de Dios C. , González‐Pinto A. , Montes J. M. , Saiz‐Ruiz J. , Prieto E. , Vieta E. ,   for the PREBIS group
Published: August 2012

Grande I, Goikolea JM, de Dios C, González‐Pinto A, Montes JM, Saiz‐Ruiz J, Prieto E, Vieta E, for the PREBIS group. Occupational disability in bipolar disorder: analysis of predictors of being on severe disablement benefit PREBIS study data).Objective:  Patients diagnosed with bipolar disorder (BD) are reported to have significant work impairment during interepisode intervals. This study was carried out to assess potential predictors of occupational disability in a longitudinal follow‐up of euthymic patients.Method:  We included 327 euthymic patients diagnosed with BD type I or type II, 226 of whom were employed and 101 were receiving a severe disablement benefit (SDB). Sociodemographic data were studied and episode recurrence was assessed along a 1‐year follow‐up. Logistic regression analysis was applied to determine predictors of receiving SDB. Cox regression was built to study recurrences.Results:  Predictors of receiving SDB were: axis II comorbidity [Odds Ratio (OR) = 2.94, CI: 1.26–6.86, P = 0.013], number of manic episodes (OR = 1.21, CI: 1.10–1.34, P < 0.001), being without stable partner (OR = 2.44, CI: 1.34–4.44, P = 0.004) and older age (OR = 1.08, CI: 1.05–1.12, P < 0.001). Bipolar patients receiving SDB presented more episodic recurrences regardless of polarity than employed bipolar patients (P = 0.002). The time until recurrence in 25% of the bipolar patients receiving SDB was 6.08 months (CI: 4.44–11.77) being 13.08 months (CI: 9.60 to –) in the employed group.Conclusion: Occupational disability in bipolar patients is associated with axis II comorbidity, more previous manic episodes, not having a stable relationship, older age, and more recurrences at 1‐year follow‐up.
Preventive and therapeutic effects of rapamycin, a mammalian target of rapamycin inhibitor, on food allergy in mice
Authors: Yamaki K. , Yoshino S. 
Published: August 2012

AbstractBackgroundBecause few curative treatments are available for food allergy, we investigated the therapeutic potential of rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, on mouse food allergy.MethodsThe preventive and therapeutic effects of oral rapamycin on anaphylactic symptoms induced by oral ovalbumin (OVA) challenge in food allergy mice were investigated. Mast cell functions in response to rapamycin were also measured in the passive systemic anaphylaxis model and bone marrow–derived mast cells (BMMCs).ResultsDaily rapamycin from the first challenge (preventive protocol) attenuated food allergy symptoms including diarrhea, anaphylactic reactions, and hypothermia in mice. The treatment decreased the challenge‐induced increases in mouse mast cell protease‐1 in serum and mast cell numbers in the intestine. Notably, the mice that already showed food allergy symptoms by previous challenges recovered from the disease with daily administration of rapamycin (therapeutic protocol). Anti‐OVA IgG1 and IgE levels in serum, as well as IFN‐γ, IL‐4, IL‐13, IL‐9, IL‐10, and IL‐17 secretion from splenocytes, were decreased by the treatments. In contrast, a single dose of rapamycin failed to affect passive systemic anaphylaxis. Spontaneous and IL‐9‐dependent survival and IgE‐induced IL‐13 secretion, but not degranulation, of BMMCs were reduced by rapamycin.ConclusionOur data show that mouse food allergy was attenuated by rapamycin through an immunosuppressive effect and inhibition of intestinal mast cell hyperplasia. Inhibition of the IL‐9 production–mast cell survival axis is one of the mechanisms of the therapeutic effect of rapamycin. Rapamycin and other mTOR inhibitors might be good candidates for therapeutic drugs for food allergy.
Prevalence and clinical relevance of local allergic rhinitis
Authors: Rondón C. , Campo P. , Galindo L. , Blanca‐López N. , Cassinello M. S. , Rodriguez‐Bada J. L. , Torres M. J. , Blanca M. 
Published: August 2012

AbstractBackgroundEvidence demonstrates the existence of local allergic rhinitis (LAR) in nonatopic patients, although its prevalence in the rhinitis population remains unknown. The aim, therefore, of this study was to evaluate the prevalence, clinical characteristics, and severity of LAR in a Spanish rhinitis population, compared with patients having classical allergic rhinitis (AR) with systemic atopy or nonallergic rhinitis (NAR).MethodsA group of 452 adult rhinitis patients were randomly selected from a total of 3860 who attended our allergy service over 1 year. A clinical questionnaire, skin prick test (SPT), spirometry, and serum total and specific IgE (sIgE) were evaluated. A nasal allergen provocation test with multiple aeroallergens (NAPT‐M), including Dermatophagoides pteronyssinus, pollens, alternaria, and dog epithelia, was performed in patients with negative SPT and serum sIgE.ResultsA total of 428 patients completed the study; 24 were excluded because of nasal hyper‐reactivity. LAR was diagnosed in 25.7%, AR in 63.1%, and NAR in 11.2%. The LAR and AR patients had a similar clinical profile: a nonsmoking woman with severe, persistent perennial rhinitis frequently associated with conjunctivitis and asthma. More than 36% of LAR patients reported rhinitis onset in childhood. NAPT‐M detected aeroallergen polysensitization in 37.3% of the LAR patients. Dermatophagoides pteronyssinus was the main sensitizing aeroallergen in LAR and AR (60% vs 54%, P > 0.05).ConclusionsLocal allergic rhinitis is a prevalent entity in patients evaluated with rhinitis. Persistent and severe symptoms associated with conjunctivitis and/or asthma and polysensitization were likely to be detected in LAR and AR.
Interleukin‐33 in allergy
Authors: Ohno Tatsukuni , Morita Hideaki , Arae Ken , Matsumoto Kenji , Nakae Susumu 
Published: August 2012

AbstractInterleukin‐33 (IL‐33) is a member of the IL‐1 cytokine family, which includes IL‐1 and IL‐18, and is considered to be important for host defense against nematodes by inducing Th2 cytokine production via the IL‐33 receptor. IL‐33 receptor is a heterodimer of IL‐1 receptor‐like 1 (IL‐1RL1; also called ST2, T1, Der4, and fit‐1) and IL‐1 receptor accessory protein (IL‐1RAcP). On the other hand, excessive and/or inappropriate production of IL‐33 is considered to be involved in the development of various disorders, such as allergic and autoimmune diseases. Unlike IL‐1β and IL‐18, IL‐33 does not seem to be secreted through the activation of inflammasomes in events such as apoptosis. However, IL‐33 is localized in the nucleus of cells and is released during tissue injury associated with necrosis. This suggests that it acts as an alarmin, like IL‐1α and high‐mobility group box chromosomal protein‐1 (HMGB‐1). This review summarizes current knowledge regarding the roles of IL‐33 in the functions of various cell types and the pathogenesis of allergy.
Is basal ultrasensitive measurement of calcitonin capable of substituting for the pentagastrin‐stimulation test?
Authors: Pina Géraldine , Dubois Séverine , Murat Arnaud , Berger Nicole , Niccoli Patricia , Peix Jean‐Louis , Cohen Régis , Guillausseau Claudine , Charrie Anne , Chabre Olivier , Cornu Catherine , Borson‐Chazot Françoise , Rohmer Vincent ,   The Groupe des Tumeurs Endocrines
Published: August 2012

SummaryObjectiveTo evaluate a second‐generation assay for basal serum calcitonin (CT) measurements compared with the pentagastrin‐stimulation test for the diagnosis of inherited medullary thyroid carcinoma (MTC) and the follow‐up of patients withMTCafter surgery. Recent American Thyroid Association recommendations suggest the use of basalCTalone to diagnose and assess follow‐up ofMTCas the pentagastrin (Pg) test is unavailable in many countries.DesignMulticentric prospective study.PatientsA total of 162 patients with basalCT<10 ng/l were included: 54 asymptomatic patients harboured noncysteine ‘rearranged during transfection’ (RET) proto‐oncogene mutations and 108 patients had entered follow‐up ofMTCafter surgery.MeasurementAll patients underwent basal andPg‐stimulatedCTmeasurements using a second‐generation assay with 5‐ng/l functional sensitivity.ResultsNinety‐five per cent of patients with basalCT≥5 ng/l and 25% of patients with basalCT<5 ng/l had a positivePg‐stimulation test (PgCT>10 ng/l). Compared with the referencePg test, basalCT≥5 ng/l had 99% specificity, a 95%‐positive predictive value but only 35% sensitivity (P < 0·0001). Overall, there were 31% less false‐negative results using a 5‐ng/l threshold for basalCTinstead of the previously used 10‐ng/l threshold.ConclusionThe ultrasensitiveCTassay reduces the false‐negative rate of basalCTmeasurements when diagnosing familialMTCand in postoperative follow‐up compared with previously used assays. However, its sensitivity to detectC‐cell disease remains lower than that of thePg‐stimulation test.
Acitretin exerted a greater influence on T‐helper (Th)1 and Th17 than on Th2 cells in treatment of psoriasis vulgaris
Authors: NIU Xinwu , CAO Wei , MA Huiqun , FENG Jie , LI Ximei , ZHANG Xinhua 
Published: August 2012

AbstractT‐helper (Th) cells, including Th1, Th2 and Th17 cells, may play an important role in the pathogenesis of psoriasis vulgaris (PV). Acitretin is an effective treatment for PV; however, its influence on Th cells during the treatment of PV is unclear. This study aimed to investigate the influence of acitretin on Th1, Th2 and Th17 cells in PV patients. PV patients (n = 30) received acitretin p.o. (20 mg/day) for 8 weeks. Sera and skin biopsies were obtained before and after treatment. Double‐labeled immunofluorescence was used to analyze T, Th1, Th2 and Th17 cells in skin lesions. Enzyme‐linked immunosorbent assay and western blot were used to analyze the expressions of interferon (IFN)‐γ, interleukin (IL)‐4 and IL‐17 in sera and skin lesions. The expressions of IFN‐γ mRNA, IL‐4 mRNA and IL‐17 mRNA in skin lesions were detected by in situ hybridization. Acitretin decreased the quantity of T, Th1 and Th17 cells in PV lesions, but had no significant influence on Th2 cells. Acitretin also decreased the expression of IFN‐γ and IL‐17 in serum and lesions. The expressions of IFN‐γ mRNA and IL‐17 mRNA decreased significantly after 8 weeks of therapy. However, acitretin had no significant influence on the expression of IL‐4 protein and mRNA. Acitretin can reverse Th1 and Th17 preponderance in PV patients to some degree. This may be due to the mechanism of acitretin on PV; however, Th2 cells were not affected by acitretin treatment.
A survey of the outcome of prophylaxis, on‐demand treatment or combined treatment in 18–35‐year old men with severe haemophilia in six countries
Authors: Noone D. , O'Mahony B. , van Dijk J. P. , Prihodova L. 
Published: August 2012

SummaryA number of studies have been published on the benefits of prophylactic treatment in adults with haemophilia. However, in many countries, it is considered as optional due to financial constraints. This survey was carried out to examine the long‐term effects of prophylaxis and the continuing benefit of the treatment into adulthood. Self‐assessed health‐related data and the EQ‐5D questionnaire measuring health utility were collected from 124 men (26.9 ± 4.6 years) from Canada (N = 40), France (N = 14), Ireland (N = 17), the Netherlands (N = 16), Poland (N = 24) and the UK (N = 13). The respondents were split into four groups: On‐Demand, <50% life on prophylaxis, ≥50% life on prophylaxis, Prophylaxis. Overall, long‐term prophylaxis results in lower presence of target joints (P ≤ 0.001), occurrence of serious bleeding episodes (P ≤ 0.05), recurring bleeding episodes (P ≤ 0.01) and requirement for surgical procedures (P ≤ 0.05). Furthermore, health utility (P ≤ 0.01) in the On‐demand group was significantly lower (P ≤ 0.01) compared to the ≥50% life on prophylaxis and the Prophylaxis group. No significant differences between countries were found except between the Netherlands and Poland, with Poland showing the lowest health utility (P ≤ 0.01) and the most problems with mobility (P ≤ 0.05) and pain/discomfort (P ≤ 0.001). The Netherlands showed the highest health utility (0.915) followed by Canada (0.791), Ireland (0.786), UK (0.768), France (0.687) and Poland (0.629). The results demonstrate consistently higher quality of life of individuals who are on long‐term prophylactic treatment when compared to on‐demand treatment or intermittent prophylaxis and on ‐demand treatment.
Instructional design or school politics? A discussion of ‘orchestration' in TEL research
Authors: Perrotta C. , Evans M.A. 
Published: August 2012

AbstractThis paper argues that the emphasis on orchestration as a metaphor for teaching in technology‐enhanced learning (TEL) environments, featured in recent academic discussions, is an opportunity to broaden the scope of the inquiry into educational technology. Drawing on sociological literature and research that investigated the systemic factors that influence the uptake of information and communication technologies in formal and informal learning contexts, the paper contends that a focus on instructional design does insufficient justice to the complexities of actual technology use in classrooms and after‐school programs. It is suggested, instead, that orchestration might better be used as a heuristic device to deepen our understandings of the relationships between power, bestowed on teachers or claimed by them through a number of strategies, educational technology, and teaching practices. The paper concludes that to fully understand this relationship and to support teachers, concern should be given equally to the existing political and cultural dynamics of TEL environments. Examples of orchestration as a political, cultural process are provided, illustrating how teachers appropriate technology and ‘innovative’ pedagogies to negotiate power.
Developmental Changes in Desensitisation of c‐Fos Expression Induced by Repeated Maternal Separation in Pre‐Weaned Mice
Authors: Horii‐Hayashi N. , Sasagawa T. , Matsunaga W. , Matsusue Y. , Azuma C. , Nishi M. 
Published: August 2012

Early‐life stress has long‐lasting effects on neuroendocrine and behaviour in adulthood. Maternal separation (MS) is used as a model of early‐life stress and daily repeated MS (RMS) for 3 h during the first two postnatal weeks is widely used in rodent studies. However, it is not fully understood whether early‐life animals desensitise/habituate to repeated stress. In the present study, we investigated the effects of daily RMS for 3 h and acute/single time MS (SMS) for 3 h on the plasma corticosterone level and c‐Fos expression in the brain in mice at different postnatal ages. Mice were subjected to: (i) RMS from postnatal day (PND) 1 to 14 (RMS14); (ii) RMS from PND14 to 21 (RMS21); (iii) SMS on PND14 (SMS14); and (iv) SMS on PND21 (SMS21). Plasma corticosterone and c‐Fos expression were examined on the final day in each experiment. The basal corticosterone levels in RMS14 and RMS21 were equal to those in respective age‐matched controls. After the final separation, the levels were significantly increased and were comparable with those after SMS14 and SMS21, respectively. Histological analysis indicated that c‐Fos expression significantly increased in many brain regions, including the paraventricular nucleus, prefrontal cortex, hippocampus, and basolateral and medial amygdale in both SMS14 and SMS21 mice. However, c‐Fos expression in RMS14 mice significantly increased in many regions, whereas such increases were hardly seen in RMS21 mice. These results indicate that repeated early‐life stress neither increases basal corticosterone, nor decreases the magnitude of the corticosterone response during the first three postnatal weeks, although desensitisation of c‐Fos expression induced by repeated stress is changed during postnatal development.
Scaling up: examining the macroecology of ectomycorrhizal fungi
Authors: KENNEDY PETER G. , MATHENY P. B. , RYBERG K. M. , HENKEL TERRY W. , UEHLING JESSIE K. , SMITH MATTHEW E. 
Published: August 2012

Ectomycorrhizal (ECM) fungi play major ecological roles in temperate and tropical ecosystems. Although the richness of ECM fungal communities and the factors controlling their structure have been documented at local spatial scales, how they vary at larger spatial scales remains unclear. In this issue of Molecular Ecology, Tedersoo et al. (2012) present the results of a meta‐analysis of ECM fungal community structure that sheds important new light on global‐scale patterns. Using data from 69 study systems and 6021 fungal species, the researchers found that ECM fungal richness does not fit the classic latitudinal diversity gradient in which species richness peaks at lower latitudes. Instead, richness of ECM fungal communities has a unimodal relationship with latitude that peaks in temperate zones. Intriguingly, this conclusion suggests the mechanisms driving ECM fungal community richness may differ from those of many other organisms, including their plant hosts. Future research will be key to determine the robustness of this pattern and to examine the processes that generate and maintain global‐scale gradients of ECM fungal richness.