bluuebunny/crossref_metadata_2025_split huggingface dataset:
Principles of transcriptome analysis and gene expression quantification: an RNA‐seq tutorial
Authors: Wolf Jochen B. W. 
Published: April 2013

AbstractGenome‐wide analyses and high‐throughput screening was long reserved for biomedical applications and genetic model organisms. With the rapid development of massively parallel sequencing nanotechnology (or next‐generation sequencing) and simultaneous maturation of bioinformatic tools, this situation has dramatically changed. Genome‐wide thinking is forging its way into disciplines like evolutionary biology or molecular ecology that were historically confined to small‐scale genetic approaches. Accessibility to genome‐scale information is transforming these fields, as it allows us to answer long‐standing questions like the genetic basis of local adaptation and speciation or the evolution of gene expression profiles that until recently were out of reach. Many in the eco‐evolutionary sciences will be working with large‐scale genomic data sets, and a basic understanding of the concepts and underlying methods is necessary to judge the work of others. Here, I briefly introduce next‐generation sequencing and then focus on transcriptome shotgun sequencing (RNA‐seq). This article gives a broad overview and provides practical guidance for the many steps involved in a typical RNA‐seq work flow from sampling, to RNA extraction, library preparation and data analysis. I focus on principles, present useful tools where appropriate and point out where caution is needed or progress to be expected. This tutorial is mostly targeted at beginners, but also contains potentially useful reflections for the more experienced.
Up regulation of serum tumor necrosis factor‐related apoptosis inducing ligand in juvenile‐onset systemic lupus erythematosus: relations with disease activity, antibodies to double ‐stranded DNA, nephritis and neutropenia
Authors: Ezzat Mohamed H. M. , EL‐Gammasy Tarek M. A. , Shaheen Kareem Y. A. , EL‐Mezdawi Ramzi A. M. , Youssef Mervat S. M. 
Published: April 2013

AbstractObjectivesApoptosis is induced by binding of death receptor ligands, members of the tumor necrosis factor (TNF) superfamily, to their cognate receptors. It is suggested that TNF‐related apoptosis inducing ligand (TRAIL) is involved in pathogenesis of juvenile‐onset systemic lupus erythematosus (JSLE). This study aimed to assess TRAIL concentrations in sera of JSLE children and to determine their potential relationship with disease activity, anti‐double‐stranded DNA (anti‐dsDNA) levels, neutropenia and renal involvement.MethodsCirculating levels of TRAIL were measured by enzyme‐linked immunosorbent assay (ELISA) in serum samples obtained from 40 JSLE patients (20 with active and 20 with inactive disease) and 20 controls.ResultsThe mean (SEM) serum TRAIL concentration in JSLE was 1750.7 (440.2) pg/mL. Serum TRAIL concentrations in patients were higher than those in controls (P < 0.01). Serum TRAIL concentrations for children with inactive disease (1854.8 [485.4] pg/mL) and those with activity (1646.6 [390.6] pg/mL) were statistically comparable. JSLE children with positive anti‐dsDNA antibodies had significantly higher TRAIL levels (mean = 1846 [456] vs. 1455 [325] pg/mL; P < 0.05). Serum TRAIL concentrations were significantly higher in classes III and IV nephritis compared to classes I and II nephritis (1970 [512] vs. 1330 [331] pg/mL; P < 0.01). Serum TRAIL concentrations in patients with neutropenia were higher than those without neutropenia (1805 [505] vs. 1516 [400] pg/mL; P = 0.042) and in controls (P = 0.024).ConclusionsOur data indicate that an increased level of TRAIL is a feature of JSLE that correlates with disease activity, anti‐dsDNA titers neutropenia and lupus nephritis.
Neuroprotective role of γ‐enolase in microglia in a mouse model of Alzheimer's disease is regulated by cathepsin X
Authors: Hafner Anja , Glavan Gordana , Obermajer Nataša , Živin Marko , Schliebs Reinhard , Kos Janko 
Published: April 2013

Summaryγ‐Enolase is a neurotrophic‐like factor promoting growth, differentiation, survival and regeneration of neurons. Its neurotrophic activity is regulated by cysteine protease cathepsin X which cleaves the C‐terminal end of the molecule. We have investigated the expression and colocalization of γ‐enolase and cathepsin X in brains of Tg2576 mice overexpressing amyloid precursor protein. In situ hybridization of γ‐enolase and cathepsin X revealed that mRNAs for both enzymes were expressed abundantly around amyloid plaques. Immunostaining demonstrated that the C‐terminally cleaved form of γ‐enolase was present in the immediate plaque vicinity, whereas the intact form, exhibiting neurotrophic activity, was observed in microglia cells in close proximity to senile plaque. The upregulation of γ‐enolase in microglial cells in response to amyloid‐β peptide (Aβ) was confirmed in mouse microglial cell line EOC 13.31 and primary microglia and medium enriched with γ‐enolase proved to be neuroprotective against Aβ toxicity; however, the effect was reversed by cathepsin X proteolytic activity. These results demonstrate an upregulation of γ‐enolase in microglia cells surrounding amyloid plaques in Tg2576 transgenic mice and demonstrate its neuroprotective role in amyloid‐β‐related neurodegeneration.
AUDIT‐C Scores as a Scaled Marker of Mean Daily Drinking, Alcohol Use Disorder Severity, and Probability of Alcohol Dependence in a U.S. General Population Sample of Drinkers
Authors: Rubinsky Anna D. , Dawson Deborah A. , Williams Emily C. , Kivlahan Daniel R. , Bradley Katharine A. 
Published: April 2013

BackgroundBrief alcohol screening questionnaires are increasingly used to identify alcohol misuse in routine care, but clinicians also need to assess the level of consumption and the severity of misuse so that appropriate intervention can be offered. Information provided by a patient's alcohol screening score might provide a practical tool for assessing the level of consumption and severity of misuse.MethodsThis post hoc analysis of data from the 2001 to 2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) included 26,546 U.S. adults who reported drinking in the past year and answered additional questions about their consumption, including Alcohol Use Disorders Identification Test—Consumption questionnaire (AUDIT‐C) alcohol screening. Linear or logistic regression models and postestimation methods were used to estimate mean daily drinking, the number of endorsed alcohol use disorder (AUD) criteria (“AUD severity”), and the probability of alcohol dependence associated with each individual AUDIT‐C score (1 to 12), after testing for effect modification by gender and age.ResultsAmong eligible past‐year drinkers, mean daily drinking, AUD severity, and the probability of alcohol dependence increased exponentially across increasing AUDIT‐C scores. Mean daily drinking ranged from < 0.1 to 18.0 drinks/d, AUD severity ranged from < 0.1 to 5.1 endorsed AUD criteria, and probability of alcohol dependence ranged from < 1 to 65% across scores 1 to 12. AUD severity increased more steeply across AUDIT‐C scores among women than men. Both AUD severity and mean daily drinking increased more steeply across AUDIT‐C scores among younger versus older age groups.ConclusionsResults of this study could be used to estimate patient‐specific consumption and severity based on age, gender, and alcohol screening score. This information could be integrated into electronic decision support systems to help providers estimate and provide feedback about patient‐specific risks and identify those patients most likely to benefit from further diagnostic assessment.
Microheterogeneity of Serum β‐Hexosaminidase in Chronic Alcohol Abusers in a Driver's License Regranting Program
Authors: Maenhout Thomas M. , Poll Anneleen , Wuyts Birgitte , Lecocq Elke , Van Vlierberghe Hans , De Buyzere Marc L. , Delanghe Joris R. 
Published: April 2013

BackgroundCarbohydrate‐deficient transferrin (CDT) is one of the best indicators for chronic alcohol abuse and detection of relapse. In this study, we explore the microheterogeneity of β‐hexosaminidase (β‐HEX) in chronic alcohol abusers in the framework of a driver's license regranting program. Studies have shown that increased serum activity of β‐HEX B (isoforms P, I, and B) may be a sensitive marker for chronic alcohol abuse. Here, we describe methodology, limitations, and correlation of β‐HEX isoforms with CDT.MethodsCDT was assayed at the central laboratory of the Ghent University Hospital by capillary zone electrophoresis, measured on the Capillarys 2™ system and was expressed as a percentage of total serum transferrin (%CDT). Serum of chronic alcohol abusers was compared to nonheavy drinkers using agarose gel isoelectric focusing (IEF). Total β‐HEX activity was assayed fluorimetrically following preparative IEF in 81 subjects. β‐HEX isoforms were investigated and compared between nonheavy drinkers and heavy drinkers.ResultsAgarose gel IEF shows additional cathodal bands in serum of chronic alcohol abusers. Mean total β‐HEX activity between pH 6.8 and 7.7, designated as HEX‐7, showed the highest correlation with %CDT (r = 0.70, p < 0.0001, n = 68). In a selected subgroup, where CDT could not be quantified (n = 13) because of an atypical electropherogram, HEX‐7 was in concordance with either estimated %CDT value or liver enzyme activities.ConclusionsIn this proof‐of‐concept study, we introduce a novel approach to quantify β‐HEX isoforms using preparative IEF and fluorimetry. A highly significant correlation of HEX‐7 and %CDT has been found. Because of exclusion of the P isoform, HEX‐7 could be a useful supplementary marker for detecting chronic alcohol abuse.
Double‐blind, placebo‐controlled, dose‐ranging study of new recombinant hypoallergenic Bet v 1 in an environmental exposure chamber
Authors: Meyer W. , Narkus A. , Salapatek A. M. , Häfner D. 
Published: April 2013

AbstractBackgroundRecombinant allergens offer a tool for improving specific immunotherapy (SIT).ObjectiveTo find the optimal dose of a new hypoallergenic folding variant of recombinant Bet v 1 (rBet v 1‐FV) as SIT for patients with birch pollen allergy.MethodsBefore SIT, thirty‐seven adult patients were exposed for eight hours in an environmental exposure chamber (EEC) to birch pollen at an average concentration of 3500 ± 500 grains/m3, then randomized to four maintenance dose groups of rBet v 1‐FV and one placebo group: 20 μg (n = 7), 80 μg (n = 8), 160 μg (n = 7), 320 μg (n = 8), and placebo (n = 7). Patients were treated for 10 weeks with weekly injections and then re‐exposed in the EEC. The optimal dose for SIT was assessed using efficacy results from the EEC, IgG responses, and tolerability.ResultsThirty‐six patients were evaluable for efficacy assessment. The total symptom score significantly decreased in all active groups compared with placebo (−18.8% for placebo patients; −71.9%, P = 0.0022 for 20 μg; −75.6%, P = 0.0007 for 80 μg; −81.8%, P = 0.0009 for 160 μg; −78.3%, P = 0.0003 for 320 μg). IgG1 increased significantly in all active groups compared to placebo. All four active doses were well tolerated, no serious adverse event occurred; two Grade II reactions, according to EAACI classification, were observed, one in each of the 160‐ and 320‐μg groups.ConclusionsConsidering efficacy, immunological response, and tolerability, a maintenance dose of 80 μg of rBet v 1‐FV appears to be the ideal dose for allergen immunotherapy in birch pollen allergic patients.
Activation of basophils by the double‐stranded RNA poly(A:U) exacerbates allergic inflammation
Authors: Ramadan A. , Pham Van L. , Machavoine F. , Dietrich C. , Alkan M. , Karasuyama H. , Schneider E. , Dy M. , Thieblemont N. 
Published: April 2013

AbstractBackgroundIt is commonly acknowledged that asthma is exacerbated by viral infections. On the other hand, basophil infiltration of lung tissues has been evidenced postmortem in cases of fatal disease, raising the question of a possible link between these two observations.ObjectivesHerein, we addressed the relationship between asthma exacerbation by viral infection and basophil activation and expansion by investigating how stimulation with the dsRNA polyadenylic/polyuridylic acid [poly(A:U)] affected basophil activities and recruitment in an allergic airway inflammation model.MethodsThe effect of dsRNA on basophils was assessed by measuring the cytokine levels produced upon stimulation. We used an OVA‐induced experimental model of allergic asthma. Airway hyperreactivity, recruitment of infiltrating cells, and cytokine production were determined in the lung of mice having received poly(A:U), as compared with untreated controls. The exacerbating effect of basophils was assessed both by adoptive transfer of poly(A:U)‐treated basophils and by their in vivo depletion with Ba103 antibody.ResultsWe found that in vitro treatment with poly(A:U) increased basophil functions by inducing TH2‐type cytokine and histamine production, whereas in vivo treatment increased peripheral basophil recruitment. Furthermore, we provide the first demonstration for increased infiltration of basophils in the lung of mice suffering from airway inflammation. In this model, disease symptoms were clearly exacerbated upon adoptive transfer of basophils exposed to poly(A:U), relative to their unstimulated counterpart. Conversely, in vivo basophil depletion alleviated disease syndromes, thus validating the transfer data.ConclusionsOur findings provide the first evidence for airway inflammation exacerbation by basophils following dsRNA stimulation.
Interleukin (IL)‐31 activates signal transducer and activator of transcription (STAT)‐1, STAT‐5 and extracellular signal‐regulated kinase 1/2 and down‐regulates IL‐12p40 production in activated human macrophages
Authors: Kasraie S. , Niebuhr M. , Werfel T. 
Published: April 2013

AbstractBackgroundInterleukin‐31 is a cytokine expressed by activated T cells. A major function of IL‐31 in atopic dermatitis (AD) is the induction of pruritus in the skin. We recently showed that IL‐31 induces pro‐inflammatory cytokines following staphylococcal exotoxins’ stimulation in human macrophages. However, signalling pathways of IL‐31 in activated human macrophages still remain unclear. The aim of the study was to investigate the signalling pathways of IL‐31 receptor as well as functional effects of IL‐31 in activated macrophages.MethodsHuman macrophages were prestimulated with staphylococcal exotoxins (SEB, α‐toxin) to up‐regulate the IL‐31 receptor with and without IL‐31. Phospho‐signal transducer and activator of transcription (pSTAT) 1/3/5, phospho‐extracellular signal‐regulated kinase (ERK 1/2), β‐actin as well as p21/WAF/Cip1 levels were determined by means of Western blot analysis. Interleukin‐12p40, IL‐12p70 and IL‐23 secretions were assessed by using an enzyme‐linked immunosorbent assay.ResultsInterleukin‐31 strongly activated STAT‐1 and 5 but not STAT‐3 in human macrophages after up‐regulation of IL‐31 receptor with staphylococcal exotoxins. p21/WAF/Cip1 expression was induced by IL‐31 in activated human macrophages. Furthermore, IL‐31 down‐regulated. IL‐12p40 secretion via ERK 1/2 phosphorylation in human macrophages following up‐regulation of IL‐31 receptor with staphylococcal exotoxins.ConclusionsThe T helper (Th) 2 cytokine IL‐31 induces pro‐inflammatory effects in activated human macrophages via STAT‐1 and 5 phosphorylation. Interleukin‐31‐induced ERK 1/2 activation contributes to the underlying mechanism of Th1 cytokine IL‐12 suppression in macrophages. This mechanism may be relevant in Th2 inflammatory responses and may help to develop therapeutic strategies in IL‐31‐associated diseases such as AD.
Effect of hypoxia exposure on the phenotypic adaptation in remodelling skeletal muscle submitted to functional overload
Authors: Chaillou T. , Koulmann N. , Meunier A. , Malgoyre A. , Serrurier B. , Beaudry M. , Bigard X. 
Published: April 2013

AbstractAimTo determine whether hypoxia influences the phenotypic adaptation of skeletal muscle induced by mechanical overload.MethodsPlantaris muscles of female rats were submitted to mechanical overload following synergist ablation. After 3 days of overload, rats were exposed to either hypobaric hypoxia (equivalent to 5500 m) or normoxia. Muscles were collected after 5, 12 and 56 days of overload (i.e. after 3, 9 and 53 days of hypoxia). We determined the myosin heavy chain (MHC) distribution, mRNA levels of myocyte‐enriched calcineurin‐integrating protein 1 (MCIP1) to indirectly assess calcineurin activity, the changes in oxidative capacity from the activities of citrate synthase (CS) and cytochrome c oxidase (COX), and the expression of regulators involved in mitochondrial biogenesis (Pgc‐1α, NRF1 and Tfam) and degradation (BNIP‐3).ResultsHypoxia did not alter the fast‐to‐slow MHC shift and the increase in calcineurin activity induced by overload; it only transiently slowed down the overload‐induced transition in MHC isoforms. Hypoxia similarly decreased CS and COX activities in overloaded and control muscles. Nuclear respiratory factor 1 (NRF1) and transcription factor A (Tfam) mRNA and BNIP‐3 protein were not influenced by hypoxia in overloaded muscles, whereas Pgc‐1α mRNA and protein contents did not correlate with changes in oxidative capacity.ConclusionHypoxia is not a critical stimulus to modulate the fast‐to‐slow MHC transition associated with overload. Thus, the impairment of the fast‐to‐slow fibre shift often observed during post‐natal development in hypoxia could be explained by the lower voluntary locomotor activity associated with hypoxia. Hypoxia alters mitochondrial oxidative capacity, but this adaptive response is similar in overloaded and control muscles.
Eccentric muscle damage increases intermuscular coherence during a fatiguing isometric contraction
Authors: Semmler J. G. , Ebert S. A. , Amarasena J. 
Published: April 2013

AbstractAimThe purpose of this study was to determine the effect of eccentric muscle damage on muscle activation patterns and intermuscular coherence during a fatiguing isometric contraction involving the elbow flexor muscles.MethodsTen young subjects participated in three experimental sessions that involved the performance of maximum voluntary contractions (MVCs), a constant‐force task at 30% MVC, and a fatiguing isometric contraction at 30% MVC. The three sessions were performed before, 2 h after and 2 days after eccentric exercise to induce muscle damage in elbow flexor muscles. Task performance was quantified with electromyography (EMG) from the elbow flexor (biceps brachii, brachialis and brachioradialis) and extensor (triceps brachii) muscles, M‐wave amplitude of biceps brachii, elbow flexor force fluctuations and endurance time of a fatiguing contraction. Intermuscular coherence during the fatiguing contraction was quantified from the rectified surface EMGs between muscle pairs.ResultsEccentric exercise resulted in several indicators of muscle damage, such as a prolonged decline in muscle strength and an increase in muscle soreness 2 days after exercise. A 29% reduction in endurance time was observed 2 h after eccentric muscle damage, which returned to baseline 2 days later. The reduced endurance time 2 h after muscle damage was accompanied by an increase in EMG‐EMG coherence between biceps brachii and brachialis muscles, which was observed at the end of the fatiguing contraction.ConclusionThese findings suggest that eccentric muscle damage produces a decrease in endurance time that is accompanied by an increase in intermuscular coherence in the presence of fatigue.
Seasonal variation of manic and depressive symptoms in bipolar disorder
Authors: Akhter Ahmed , Fiedorowicz Jess G , Zhang Tao , Potash James B , Cavanaugh Joseph , Solomon David A , Coryell William H 
Published: April 2013

ObjectivesAnalyses of seasonal variation of manic and depressive symptoms in bipolar disorder in retrospective studies examining admission data have yielded conflicting results. We examined seasonal variation of mood symptoms in a prospective cohort with long‐term follow‐up: the Collaborative Depression Study (CDS).MethodsThe CDS included participants from five academic centers with a prospective diagnosis of bipolar I or II disorder. The sample was limited to those who were followed for at least 10 years of annual or semi‐annual assessments. Time series analyses and autoregressive integrated moving average (ARIMA) models were used to assess seasonal patterns of manic and depressive symptoms.ResultsA total of 314 individuals were analyzed (bipolar I disorder, n = 202; bipolar II disorder, n = 112), with both disorders exhibiting the lowest frequency of depressive symptoms in summer and the highest around the winter solstice, though the winter peak in symptoms was statistically significant only with bipolar I disorder. Variation of manic symptoms was more pronounced in bipolar II disorder, with a significant peak in hypomanic symptomatology in the months surrounding the fall equinox.ConclusionsSignificant seasonal variation exists in bipolar disorder, with manic/hypomanic symptoms peaking around the fall equinox and depressive symptoms peaking in the months surrounding the winter solstice in bipolar I disorder.
Majority Children's Evaluation of Acculturation Preferences of Immigrant and Emigrant Peers
Authors: Verkuyten Maykel , Thijs Jochem , Sierksma Jellie 
Published: April 2013

Using an experimental design, native majority group children (8–13 years,N = 842) evaluated acculturation strategies (assimilation, integration, and separation) adopted by immigrant and emigrant peers. There were medium to large effects of the perceived acculturation strategies on children's peer evaluations. Overall, assimilation was valued most, followed by integration and separation. These effects were in part mediated by perceived national belonging. In addition, the effects were stronger for lower status compared to higher status immigrant groups, and for children with higher compared to lower national identification. For emigrants, separation was valued most, followed by integration and assimilation. This indicates that the intergroup processes rather than migration per se are important for children's acculturation perceptions and evaluations.
Perceived triggers of asthma: key to symptom perception and management
Authors: Janssens T. , Ritz T. 
Published: April 2013

SummaryAdequate asthma management depends on an accurate identification of asthma triggers. A review of the literature on trigger perception in asthma shows that individuals vary in their perception of asthma triggers and that the correlation between self‐reported asthma triggers and allergy tests is only modest. In this article, we provide an overview of psychological mechanisms involved in the process of asthma triggers identification. We identify sources of errors in trigger identification and targets for behavioural interventions that aim to improve the accuracy of asthma trigger identification and thereby enhance asthma control.
The Impact of Multiple Risk Factors on Young Children's Cognitive and Behavioural Development
Authors: Sabates Ricardo , Dex Shirley 
Published: April 2013

The paper maps out 10 risk factors measuring deficits in parent–child interaction, family–child interaction and the home environment. The prevalence of risk factor combinations is quantified using theUKMillennium Cohort Study data. In 2001, 28 per cent of families with young children were facing two or more risk factors at age 9–10 months old. Each combination of multiple risk factors accounted for a very small proportion of allMCSfamilies. Specific risk factors were associated with particular developmental outcomes at age 5 and with changes from age 3 to age 5, but all leading to worse outcomes. The great diversity of risk‐factor combinations and their very small prevalence make the tasks of identifying such families and defining eligibility for support very difficult for policy‐makers. These results support the large body of policy literature advocating early intervention to improve children's development.