bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychometric Properties of the Index of Relocation Adjustment
Authors: Bekhet Abir K. , Zauszniewski Jaclene A.
Published: June 2012

More and more American older adults are relocating to retirement communities, and they experience challenges in adjusting to new surroundings that may increase their depression and mortality. An instrument not previously tested in the United States, the Index of Relocation Adjustment (IRA), may help in early identification of poor relocation adjustment. This study examined the psychometric properties of the IRA using secondary data from a convenience sample of 104 older adults who relocated to 6 retirement communities in Northeast Ohio. Cronbach’s alpha was .86. The IRA was correlated with measures of positive cognitions ( r = .48, p < .01) and relocation controllability ( r = –.62, p < .01), suggesting construct validity. Results indicated a single factor reflecting relocation adjustment with loadings for all items ranging from .62 to .83. The IRA is potentially useful as a screening measure for early detection of poor adjustment among relocated older adults.
Incidence of Gastric Mucosal Injury as Measured by Reactance in Critically Ill Patients
Authors: Beltran Nohra E. , Ceron Ulises , Sanchez-Miranda Gustavo , Remolina Miguel , Godinez Maria M. , Peralta Itzel Y. , Sacristan Emilio
Published: June 2012

Gastric reactance has been proposed as a measure of mucosal ischemic injury in the critically ill. The purpose of this study was to evaluate the incidence of gastric mucosal injury as measured by gastric reactance in different subgroups of critical patients. We studied 100 adult patients admitted to 7 different hospital intensive care units, requiring a nasogastric tube. Gastric impedance measurements were continuously obtained from each patient for 24 hours. Patients were managed based on conventional protocols by hospital staff, blinded to the changes in gastric impedance parameters. The low-frequency central reactance ( XL) reflects tissue edema caused by prolonged ischemia. The previously reported threshold of XL ≥ 13 − jΩ was used to classify injured mucosa; 80% of all patients had mean XL above this threshold. No significant differences were found in the incidence of mucosal ischemia between medical versus surgical, hemodynamic versus respiratory or neurological patients. Significant lower urine output was found in patients with XL above threshold ( P < .01); also, there was a significant effect of fluid balance in those patients ( P < .05). More complicated patients had higher average reactance. This study shows that gastric ischemia as estimated by gastric reactance has a very high incidence in the critically ill, independently of the reason for admission. High reactance is related with higher morbidity in agreement with other reports using different methods of assessing splanchnic hypoperfusion in this patient population.
Clinical Evidence of Early Acute Lung Injury Often Precedes the Diagnosis of ALI
Authors: Rackley Craig R. , Levitt Joseph E. , Zhuo Hanjing , Matthay Michael A. , Calfee Carolyn S.
Published: June 2012

Background:

Acute lung injury (ALI) has been primarily defined in patients who require positive pressure ventilation. As a result, the clinical characteristics of patients with early ALI (EALI) prior to the need for mechanical ventilation have not been well characterized. Early identification of patients with ALI and the impending need for positive pressure ventilation could define a study population for trials of novel therapies.

Methods:

We analyzed clinical data from 93 patients at 12, 24, and 48 hours prior to the standard diagnosis of ALI. The time of ALI diagnosis was defined when patients were mechanically ventilated and met the 1994 American–European Consensus Conference diagnostic criteria for ALI.

Results:

The majority of patients with ALI presented to the hospital more than 24 hours prior to developing ALI. Specifically, 73% presented more than 12 hours prior to diagnosis, and 57% presented more than 24 hours prior to diagnosis. Of patients hospitalized for at least 12 hours prior to ALI diagnosis, 94% had either bilateral infiltrates on chest radiograph, tachypnea, or an oxygen requirement greater than 2 L/min; 79% and 48% had 2 and 3 of these abnormalities, respectively.

Conclusion:

The majority of hospitalized patients who are destined to develop ALI demonstrate tachypnea, increased oxygen requirements, and/or bilateral infiltrates on chest radiograph more than 12 hours prior to meeting criteria for diagnosis. Some patients with EALI may be identified prior to meeting diagnostic criteria during a potential therapeutic window.
From the Trenches
Authors: Thomsen David J.
Published: June 2012

Compensation and benefits make up over 50% of most organizations’ costs and like stars in the Heaven, exist among physical forces that can be predict future positions in the sky mathematically. The Rule of 72 (divide an interest rate into 72 to ascertain the years to double a sum) affects wages and salaries earned, college debt repayments, executive compensation, healthcare costs, America’s use of “non-employees,” wealth accumulation, disability recipients, retirement funding and a host of other compensation & benefit issues. Examine and review what the future portends if no changes in policies and practices are enacted (which has been the author’s 40 year career history), as the future is already decided (because not making changes are in themselves, decisions).
Oxidative stress induced in the workers of natural gas refineries, no role for GSTM1 and GSTT1 polymorphisms
Authors: Mandegary A , Sezavar M , Saeedi A , Amirheidari B , Naghibi B
Published: June 2012

Oxidative stress has an important role in the pathophysiology of many occupational diseases. In this controlled exposure study, the intensity of oxidative stress biomarkers was assessed in the workers of natural sweet and sour gas refineries (SwGR and SoGR, respectively) and compared with controls. In addition, the role of gluthatione S-transferase M1 (GSTM1)-null and GSTT1-null polymorphisms on the intensity of oxidative stress and liver function tests (LFTs) was investigated. Blood samples were taken and measured for lipid peroxidation (LPO) level, total antioxidant capacity (TAC) and total thiol molecules (TTMs). GSTM1- and GSTT1-null genotypes were determined using polymerase chain reaction. LPO was significantly ( p < 0.05) higher in the workers of SoGR. TAC was significantly lower in SwGR subjects ( p < 0.001). TTMs were significantly lower in SoGR and SwGR subjects. Among LFTs, activities of aspartate aminotransferase and alanine aminotransferase but not alkaline phosphatase were elevated significantly ( p < 0.001) in SoGR subjects. Multivariate linear regression revealed no association between studied polymorphisms, oxidative stress biomarkers, and LFTs. These results indicate that working in the SoGR and SwGR can lead to oxidative stress and abnormal LFTs. Continuous monitoring of natural gas workers for probable ongoing problems is therefore suggested.
Restricted ROC curves are useful tools to evaluate the performance of tumour markers
Authors: Parodi S , Muselli M , Carlini B , Fontana V , Haupt R , Pistoia V , Corrias MV
Published: June 2012

In Clinical Epidemiology, receiver operating characteristic (ROC) analysis is a standard approach for the evaluation of the performance of diagnostic tests for binary classification based on a tumour marker distribution. The area under a ROC curve is a popular indicator of test accuracy, but its use has been questioned when the curve is asymmetric. This situation often happens when the marker concentrations overlap in the two groups under study in the range of low specificity, corresponding to a subset of values useless for classification purposes (non-informative values). The partial area under the curve at a high specificity threshold has been proposed as an alternative, but a method to identify an optimal cut-off that separates informative from non-informative values is not yet available. In this study, a new statistical approach is proposed to perform this task. Furthermore, a statistical test associated with the area under a ROC curve corresponding to informative values only (restricted ROC curve) is provided and its properties are explored by extensive simulations. Finally, the proposed method is applied to a real data set containing peripheral blood levels of six tumour markers proposed for the diagnosis of neuroblastoma. A new approach to combine couples of markers for classification purposes is also illustrated.
Beyond here-and-now: extending shared physical experiences to shared conceptual experiences
Authors: Schulz Ruth , Wyeth Gordon , Wiles Janet
Published: June 2012

For robots to use language effectively, they need to refer to combinations of existing concepts, as well as concepts that have been directly experienced. In this paper, we introduce the term generative grounding to refer to the establishment of shared meaning for concepts referred to using relational terms. We investigated a spatial domain, which is both experienced and constructed using mobile robots with cognitive maps. The robots, called Lingodroids, established lexicons for locations, distances, and directions through structured conversations called where-are-we, how-far, what-direction, and where-is-there conversations. Distributed concept construction methods were used to create flexible concepts, based on a data structure called a distributed lexicon table. The lexicon was extended from words for locations, termed toponyms, to words for the relational terms of distances and directions. New toponyms were then learned using these relational operators. Effective grounding was tested by using the new toponyms as targets for go-to games, in which the robots independently navigated to named locations. The studies demonstrate how meanings can be extended from grounding in shared physical experiences to grounding in constructed cognitive experiences, giving the robots a language that refers to their direct experiences, and to constructed worlds that are beyond the here-and-now.
Experience on Using Prothrombin Complex Concentrate in Urgent Warfarin Reversal
Authors: Haghpanah Sezaneh , Karimi Mehran , Bordbar Mohammadreza , Kamfiroozi Rosa , Asgharzadeh Hafezeh
Published: June 2012

We evaluated the effectiveness and safety of prothrombin complex concentrate (PCC) in urgent warfarin reversal in Iran. This is a nonrandomized, pre–post intervention study. Thirty-seven high-risk patients with prolonged international normalized ratio ([INR] >8) or with bleeding symptoms were enrolled in this study. Prothrombin complex concentrate was infused with a dose of 22.4 ± 11.2 IU/kg. The INR was measured 30 minutes postinfusion. Mean age of the participants was 63.9 ± 14.5 (22-89 years). After 30 minutes of PCC injection, INR reversed to <3.5 in 31 patients (84%) in whom 12 patients achieved INR 1.5 to 2.5, and 19 patients achieved INR 2.5 to 3.5. Bleeding symptoms were subsided during 0.5 hour after PCC infusion in patients with hemorrhagic symptoms. Not any adverse reaction was observed in patients during 3-month follow-up. Our experience in use of single injection of PCC in high-risk patients with prolonged INR or with bleeding symptoms was successful without any complication.
(Re)appropriating The Petroglyphs: Commercial representations of a cultural landscape
Authors: Dickinson Elizabeth
Published: June 2012

This article examines the case of the Albuquerque Petroglyphs to explore how government and business commercially appropriate and reappropriate cultural landscapes for use in capitalistic development. The Petroglyph National Monument was established in Albuquerque, New Mexico, to protect an area and rock carvings from looting and development. Stakeholders evoked Pueblo and Spanish sacredness in their protection arguments to establish the monument. When governmental officials then controversially moved protected rock carvings to build a commuter road through the monument to access development, the rights of developers and consumers were privileged over Pueblo and environmental groups. Developers then drew from governmental framings and evoked a heightened Spanish colonial and commercial heritage to market nearby homes to consumers. This article argues that protection discourses can contribute to, rather than restrict, subsequent commercial development.
Grief, commiseration, and consumption following the death of a celebrity
Authors: Radford Scott K. , Bloch Peter H.
Published: June 2012

Celebrated individuals often take on a sacred status, producing intense feelings among their fans. Because celebrities are usually protected and distant, their fans turn to celebrity-related products, which themselves may become cherished and sacred. After a celebrity dies, relevant products become even more significant as remedies for feelings of loss. This research examined expressions of grief and consumption-related emotions posted on internet message boards in response to the death of race car driver Dale Earnhardt, Sr. The research finds that fans use two processes: introjection and incorporation to deal with the loss of the celebrity. These processes help fans cope with grief and serve as narratives in their post-death self-identity creation, and also contribute to the mythology of the celebrity after death.
Rights, goals, and capabilities
Authors: van Hees Martin
Published: June 2012

This article analyses the relationship between rights and capabilities in order to get a better grasp of the kind of consequentialism that the capability theory represents. Capability rights have been defined as rights that have a capability as their object (rights to capabilities). Such a definition leaves the relationship between capabilities and rights to a great extent underspecified since nothing is said about the nature of those rights. Hence, it is not precluded that they are mere negative liberties, something that capability theorists deny. On the other hand, to say that all capability rights are substantive in the sense that they themselves are capabilities (rights as capabilities) will in a significant number of cases fail to match well with our intuitions. This article presents an account of the relationship between rights and capabilities that avoids these problems of underspecification and of plausibility, respectively. First, it is argued that to take the idea of capability rights seriously, three new ‘list issues’ need to be addressed. Second, developing a point made by Nussbaum, it is argued that capability rights are to be defined as being purely instrumental. Whereas the resulting analysis of capability rights solves the problems of underspecification and plausibility, it raises doubts about the claim that the capability approach gives more importance to rights than do traditional forms of consequentialism.
Investigation of Eating Actions of People With Dementia From the Viewpoint of Self-Awareness
Authors: Yokoi Teruo , Haraguchi Eriko , Hashimoto Tomohiro , Okamura Hitoshi
Published: June 2012

The key to improve the quality of life of people with dementia and caregivers is whether caregivers can understand the meanings of the puzzling words and deeds of people with dementia. Therefore, 2 of the authors observed and wrote down the puzzling words and deeds of 28 people with dementia in eating scenes, and these words and deeds were interpreted using our original model consisting of “theory of mind,” “self-evaluation,” and “self-consciousness.” The results indicated that the bases for why caregivers perceive the words and deeds of people with dementia in eating scenes as puzzling are (1) those unable to pass the task of self-evaluation cannot evaluate their own eating situations in comparison with social standards, and the food culture collapses and (2) those unable to pass the task of self-consciousness cannot perceive through their senses.
Solution-Focused Brief Therapy for Depression and Alcohol Dependence
Authors: Spilsbury Georgina
Published: June 2012

This case study employs solution-focused brief therapy (SFBT) to alleviate depressive symptoms in an alcohol-dependent patient with comorbid personality disorder. Alcohol dependence and depression are frequent comorbid conditions in patients presenting for treatment. For some of these, personality disorders may further complicate treatment and even present a barrier to patients seeking or being offered treatment. In the case described, the patient only sought treatment after his gingivitis led to discovery of liver damage. In addition to SFBT, the patient was prescribed acamprosate to assist with abstinence from alcohol and fluoxetine for depression. Following three sessions of SFBT spaced at 1-month intervals, the patient reported maintaining abstinence from alcohol. His symptoms of depression as measured by Depression Anxiety Stress Scale reduced from severe to normal range, and he reported a reduction in the frequency and intensity of dark thoughts that had previously plagued him when sober. Outcomes were maintained 12 months following treatment.
Comparison of three dimensional and radiographic measurements in the analysis of distal radius malunion
Authors: Miyake J. , Murase T. , Yamanaka Y. , Moritomo H. , Sugamoto K. , Yoshikawa H.
Published: June 2012

To estimate the accuracy of radiographic deformity evaluation for distal radius malunion, we compared the results obtained from radiographic measurements (palmar tilt, radial angle, and ulnar variance) with those from the three-dimensional (3D) method using computer bone models in 20 dorsally tilted malunions. Dorsal tilt deformity, radial tilt deformity, and shortening deformity were calculated using the unaffected side as a reference. The 3D method showed a slightly lower value for dorsal tilt deformity than the radiographic evaluation, but the difference was < 10° in all cases. In patients with dorsal tilt ≥ 40°, notable differences in radial tilt evaluation were observed between the two methods compared with patients with less dorsal tilt. The 3D shortening showed positive correlations with radiographic evaluation, but a discrepancy of ≥ 2 mm was observed in eight cases. Palmar tilt is reliable for surgical planning, but radial angle and ulnar variance may be less accurate than previously thought.
How I treat immune thrombocytopenia: the choice between splenectomy or a medical therapy as a second-line treatment
Authors: Ghanima Waleed , Godeau Bertrand , Cines Douglas B. , Bussel James B.
Published: June 2012

The paradigm for managing primary immune thrombocytopenia (ITP) in adults has changed with the advent of rituximab and thrombopoietin receptor agonists (TPO-RAs) as options for second-line therapy. Splenectomy continues to provide the highest cure rate (60%-70% at 5+ years). Nonetheless, splenectomy is invasive, irreversible, associated with postoperative complications, and its outcome is currently unpredictable, leading some physicians and patients toward postponement and use of alternative approaches. An important predicament is the lack of studies comparing second-line options to splenectomy and to each other. Furthermore, some adults will improve spontaneously within 1-2 years. Rituximab has been given to more than 1 million patients worldwide, is generally well tolerated, and its short-term toxicity is acceptable. In adults with ITP, 40% of patients are complete responders at one year and 20% remain responders at 3-5 years. Newer approaches to using rituximab are under study. TPO-RAs induce platelet counts > 50 000/μL in 60%-90% of adults with ITP, are well-tolerated, and show relatively little short-term toxicity. The fraction of TPO-RA–treated patients who will be treatment-free after 12-24 months of therapy is unknown but likely to be low. As each approach has advantages and disadvantages, treatment needs to be individualized, and patient participation in decision-making is paramount.
Stress hematopoiesis reveals abnormal control of self-renewal, lineage bias, and myeloid differentiation in Mll partial tandem duplication (Mll-PTD) hematopoietic stem/progenitor cells
Authors: Zhang Yue , Yan Xiaomei , Sashida Goro , Zhao Xinghui , Rao Yalan , Goyama Susumu , Whitman Susan P. , Zorko Nicholas , Bernot Kelsie , Conway Rajeana M. , Witte David , Wang Qian-fei , Tenen Daniel G. , Xiao Zhijian , Marcucci Guido , Mulloy James C. , Grimes H. Leighton , Caligiuri Michael A. , Huang Gang
Published: June 2012

One mechanism for disrupting the MLL gene in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is through partial tandem duplication (MLL-PTD); however, the mechanism by which MLL-PTD contributes to MDS and AML development and maintenance is currently unknown. Herein, we investigated hematopoietic stem/progenitor cell (HSPC) phenotypes of Mll-PTD knock-in mice. Although HSPCs (Lin−Sca1+Kit+ (LSK)/SLAM+ and LSK) in MllPTD/WT mice are reduced in absolute number in steady state because of increased apoptosis, they have a proliferative advantage in colony replating assays, CFU-spleen assays, and competitive transplantation assays over wild-type HSPCs. The MllPTD/WT-derived phenotypic short-term (ST)–HSCs/multipotent progenitors and granulocyte/macrophage progenitors have self-renewal capability, rescuing hematopoiesis by giving rise to long-term repopulating cells in recipient mice with an unexpected myeloid differentiation blockade and lymphoid-lineage bias. However, MllPTD/WT HSPCs never develop leukemia in primary or recipient mice, suggesting that additional genetic and/or epigenetic defects are necessary for full leukemogenic transformation. Thus, the Mll-PTD aberrantly alters HSPCs, enhances self-renewal, causes lineage bias, and blocks myeloid differentiation. These findings provide a framework by which we can ascertain the underlying pathogenic role of MLL-PTD in the clonal evolution of human leukemia, which should facilitate improved therapies and patient outcomes.
Ancient origin of the divergent forms of leucyl-tRNA synthetases in the Halobacteriales
Authors: Andam Cheryl P , Harlow Timothy J , Papke R Thane , Gogarten J Peter
Published: June 2012

Background

Horizontal gene transfer (HGT) has greatly impacted the genealogical history of many lineages, particularly for prokaryotes, with genes frequently moving in and out of a line of descent. Many genes that were acquired by a lineage in the past likely originated from ancestral relatives that have since gone extinct. During the course of evolution, HGT has played an essential role in the origin and dissemination of genetic and metabolic novelty.

Results

Three divergent forms of leucyl-tRNA synthetase (LeuRS) exist in the archaeal order Halobacteriales, commonly known as haloarchaea. Few haloarchaeal genomes have the typical archaeal form of this enzyme and phylogenetic analysis indicates it clusters within the Euryarchaeota as expected. The majority of sequenced halobacterial genomes possess a bacterial form of LeuRS. Phylogenetic reconstruction puts this larger group of haloarchaea at the base of the bacterial domain. The most parsimonious explanation is that an ancient transfer of LeuRS took place from an organism related to the ancestor of the bacterial domain to the haloarchaea. The bacterial form of LeuRS further underwent gene duplications and/or gene transfers within the haloarchaea, with some genomes possessing two distinct types of bacterial LeuRS. The cognate tRNALeualso reveals two distinct clusters for the haloarchaea; however, these tRNALeuclusters do not coincide with the groupings found in the LeuRS tree, revealing that LeuRS evolved independently of its cognate tRNA.

Conclusions

The study of leucyl-tRNA synthetase in haloarchaea illustrates the importance of gene transfer originating in lineages that went extinct since the transfer occurred. The haloarchaeal LeuRS and tRNALeudid not co-evolve.
Identification and validation of copy number variants using SNP genotyping arrays from a large clinical cohort
Authors: Valsesia Armand , Stevenson Brian J , Waterworth Dawn , Mooser Vincent , Vollenweider Peter , Waeber Gérard , Jongeneel C Victor , Beckmann Jacques S , Kutalik Zoltán , Bergmann Sven
Published: June 2012

Background

Genotypes obtained with commercial SNP arrays have been extensively used in many large case-control or population-based cohorts for SNP-based genome-wide association studies for a multitude of traits. Yet, these genotypes capture only a small fraction of the variance of the studied traits. Genomic structural variants (GSV) such as Copy Number Variation (CNV) may account for part of the missing heritability, but their comprehensive detection requires either next-generation arrays or sequencing. Sophisticated algorithms that infer CNVs by combining the intensities from SNP-probes for the two alleles can already be used to extract a partial view of such GSV from existing data sets.

Results

Here we present several advances to facilitate the latter approach. First, we introduce a novel CNV detection method based on a Gaussian Mixture Model. Second, we propose a new algorithm, PCA merge, for combining copy-number profiles from many individuals into consensus regions. We applied both our new methods as well as existing ones to data from 5612 individuals from the CoLaus study who were genotyped on Affymetrix 500K arrays. We developed a number of procedures in order to evaluate the performance of the different methods. This includes comparison with previously published CNVs as well as using a replication sample of 239 individuals, genotyped with Illumina 550K arrays. We also established a new evaluation procedure that employs the fact that related individuals are expected to share their CNVs more frequently than randomly selected individuals. The ability to detect both rare and common CNVs provides a valuable resource that will facilitate association studies exploring potential phenotypic associations with CNVs.

Conclusion

Our new methodologies for CNV detection and their evaluation will help in extracting additional information from the large amount of SNP-genotyping data on various cohorts and use this to explore structural variants and their impact on complex traits.
An elm EST database for identifying leaf beetle egg-induced defense genes
Authors: Büchel Kerstin , McDowell Eric , Nelson Will , Descour Anne , Gershenzon Jonathan , Hilker Monika , Soderlund Carol , Gang David R , Fenning Trevor , Meiners Torsten
Published: June 2012

Background

Plants can defend themselves against herbivorous insects prior to the onset of larval feeding by responding to the eggs laid on their leaves. In the European field elm (Ulmus minor), egg laying by the elm leaf beetle (Xanthogaleruca luteola) activates the emission of volatiles that attract specialised egg parasitoids, which in turn kill the eggs. Little is known about the transcriptional changes that insect eggs trigger in plants and how such indirect defense mechanisms are orchestrated in the context of other biological processes.

Results

Here we present the first large scale study of egg-induced changes in the transcriptional profile of a tree. Five cDNA libraries were generated from leaves of (i) untreated control elms, and elms treated with (ii) egg laying and feeding by elm leaf beetles, (iii) feeding, (iv) artificial transfer of egg clutches, and (v) methyl jasmonate. A total of 361,196 ESTs expressed sequence tags (ESTs) were identified which clustered into 52,823 unique transcripts (Unitrans) and were stored in a database with a public web interface. Among the analyzed Unitrans, 73% could be annotated by homology to known genes in the UniProt (Plant) database, particularly to those fromVitis,Ricinus,PopulusandArabidopsis. Comparativein silicoanalysis among the different treatments revealed differences in Gene Ontology term abundances. Defense- and stress-related gene transcripts were present in high abundance in leaves after herbivore egg laying, but transcripts involved in photosynthesis showed decreased abundance. Many pathogen-related genes and genes involved in phytohormone signaling were expressed, indicative of jasmonic acid biosynthesis and activation of jasmonic acid responsive genes. Cross-comparisons between different libraries based on expression profiles allowed the identification of genes with a potential relevance in egg-induced defenses, as well as other biological processes, including signal transduction, transport and primary metabolism.

Conclusion

Here we present a dataset for a large-scale study of the mechanisms of plant defense against insect eggs in a co-evolved, natural ecological plant–insect system. The EST database analysis provided here is a first step in elucidating the transcriptional responses of elm to elm leaf beetle infestation, and adds further to our knowledge on insect egg-induced transcriptomic changes in plants. The sequences identified in our comparative analysis give many hints about novel defense mechanisms directed towards eggs.
Use of mRNA-seq to discriminate contributions to the transcriptome from the constituent genomes of the polyploid crop species Brassica napus
Authors: Higgins Janet , Magusin Andreas , Trick Martin , Fraser Fiona , Bancroft Ian
Published: June 2012

Background

Polyploidy often results in considerable changes in gene expression, both immediately and over evolutionary time. New phenotypes often arise with polyploid formation and may contribute to the fitness of polyploids in nature or their selection for use in agriculture. Oilseed rape (Brassica napus) is widely used to study the process of polyploidy both in artificially resynthesised and natural forms. mRNA-Seq, a recently developed approach to transcriptome profiling using deep-sequencing technologies is an alternative to microarrays for the study of gene expression in a polyploid.

Results

Illumina mRNA-Seq is comparable to microarray analysis for transcript quantification but has increased sensitivity and, very importantly, the potential to distinguish between homoeologous genes in polyploids. Using a novel curing process, we adapted a reference sequence that was a consensus derived from ESTs from bothBrassicaA and C genomes to one containing separate A and C genome versions for each of the 94,558 original unigenes. We aligned reads fromB. napusto this cured reference, finding 38% more reads mapping from resynthesised lines and 28% more reads mapping from natural lines. Where the A and C versions differed at single nucleotide positions, termed inter-homoeologue polymorphisms (IHPs), we were able to apportion expression in the polyploid between the A and C genome homoeologues. 43,761 unigenes contained at least one IHP, with a mean frequency of 10.5 per kb unigene sequence. 6,350 of the unigenes with IHPs were differentially expressed between homoeologous gene pairs in resynthesisedB. napus. 3,212 unigenes showed a similar pattern of differential expression across a range of naturalB. napuscrop varieties and, of these, 995 were in common with resynthesisedB. napus.Functional classification showed over-representation in gene ontology categories not associated with dosage-sensitivity.

Conclusion

mRNA-Seq is the method of choice for measuring transcript abundance in polyploids due to its ability to measure the contributions of homoeologues to gene expression. The identification of large numbers of differentially expressed genes in both a newly resynthesised polyploid and naturalB. napusconfirms that there are both immediate and long-term alterations in the expression of homoeologous gene pairs following polyploidy.
Transcriptomic analysis of the stress response to weaning at housing in bovine leukocytes using RNA-seq technology
Authors: O’Loughlin Aran , Lynn David J , McGee Mark , Doyle Sean , McCabe Matthew , Earley Bernadette
Published: June 2012

Background

Weaning of beef calves is a necessary husbandry practice and involves separating the calf from its mother, resulting in numerous stressful events including dietary change, social reorganisation and the cessation of the maternal-offspring bond and is often accompanied by housing. While much recent research has focused on the physiological response of the bovine immune system to stress in recent years, little is known about the molecular mechanisms modulating the immune response. Therefore, the objective of this study was to provide new insights into the molecular mechanisms underlying the physiological response to weaning at housing in beef calves using Illumina RNA-seq.

Results

The leukocyte transcriptome was significantly altered for at least 7 days following either housing or weaning at housing. Analysis of differentially expressed genes revealed that four main pathways, cytokine signalling, transmembrane transport, haemostasis and G-protein-coupled receptor (GPRC) signalling were differentially regulated between control and weaned calves and underwent significant transcriptomic alterations in response to weaning stress on day 1, 2 and 7. Of particular note, chemokines, cytokines and integrins were consistently found to be up-regulated on each day following weaning. Evidence for alternative splicing of genes was also detected, indicating a number of genes involved in the innate and adaptive immune response may be alternatively transcribed, including those responsible for toll receptor cascades and T cell receptor signalling.

Conclusions

This study represents the first application of RNA-Seq technology for genomic studies in bovine leukocytes in response to weaning stress. Weaning stress induces the activation of a number of cytokine, chemokine and integrin transcripts and may alter the immune system whereby the ability of a number of cells of the innate and adaptive immune system to locate and destroy pathogens is transcriptionally enhanced. Stress alters the homeostasis of the transcriptomic environment of leukocytes for at least 7 days following weaning, indicating long term effects of stress exposure in the bovine. The identification of gene signature networks that are stress activated provides a mechanistic framework to characterise the multifaceted nature of weaning stress adaptation in beef calves. Thus, capturing subtle transcriptomic changes provides insight into the molecular mechanisms that underlie the physiological response to weaning stress.
Functional diversification of yeast telomere associated protein, Rif1, in higher eukaryotes
Authors: Sreesankar Easwaran , Senthilkumar Ramamoorthy , Bharathi Vellaichamy , Mishra Rakesh K , Mishra Krishnaveni
Published: June 2012

Background

Telomeres are nucleoprotein complexes at the end of linear eukaryotic chromosomes which maintain the genome integrity by regulating telomere length, preventing recombination and end to end fusion events. Multiple proteins associate with telomeres and function in concert to carry out these functions. Rap1 interacting factor 1 (Rif1), was identified as a protein involved in telomere length regulation in yeast. Rif1 is conserved upto mammals but its function has diversified from telomere length regulation to maintenance of genome integrity.

Results

We have carried out detailed bioinformatic analyses and identified Rif1 homologues in 92 organisms from yeast to human. We identified Rif1 homologues in Drosophila melanogaster, even though fly telomeres are maintained by a telomerase independent pathway. Our analysis shows that Drosophila Rif1 (dRif1) sequence is phylogenetically closer to the one of vertebrates than yeast and has identified a few Rif1 specific motifs conserved through evolution. This includes a Rif1 family specific conserved region within the HEAT repeat domain and a motif involved in protein phosphatase1 docking. We show that dRif1 is nuclear localized with a prominent heterochromatin association and unlike human Rif1, it does not respond to DNA damage by localizing to damaged sites. To test the evolutionary conservation of dRif1 function, we expressed the dRif1 protein in yeast and HeLa cells. In yeast, dRif1 did not perturb yeast Rif1 (yRif1) functions; and in HeLa cells it did not colocalize with DNA damage foci.

Conclusions

Telomeres are maintained by retrotransposons in all Drosophila species and consequently, telomerase and many of the telomere associated protein homologues are absent, including Rap1, which is the binding partner of Rif1. We found that a homologue of yRif1 protein is present in fly and dRif1 has evolutionarily conserved motifs. Functional studies show that dRif1 responds differently to DNA damage, implying that dRif1 may have a different function and this may be conserved in other organisms as well.
TGFβ signaling plays a critical role in promoting alternative macrophage activation
Authors: Gong Dapeng , Shi Wei , Yi Sun-ju , Chen Hui , Groffen John , Heisterkamp Nora
Published: June 2012

Background

Upon stimulation with different cytokines, macrophages can undergo classical or alternative activation to become M1 or M2 macrophages. Alternatively activated (or M2) macrophages are defined by their expression of specific gene products and play an important role in containing inflammation, removing apoptotic cells and repairing tissue damage. Whereas it is well-established that IL-4 can drive alternative activation, if lack of TGFβ signaling at physiological levels affects M2 polarization has not been addressed.

Results

Vav1-Cre x TβRIIfx/fxmice, lacking TβRII function in hematopoietic cells, exhibited uncontrolled pulmonary inflammation and developed a lethal autoimmune syndrome at young age. This was accompanied by significantly increased numbers of splenic neutrophils and T cells as well as elevated hepatic macrophage infiltration and bone marrow monocyte counts.TβRII-/-CD4+and CD8+T-cells in the lymph nodes and spleen expressed increased cell surface CD44, and CD69 was also higher on CD4+lymph node T-cells. Loss of TβRII in bone marrow-derived macrophages (BMDMs) did not affect the ability of these cells to perform efferocytosis. However, these cells were defective in basal and IL-4-inducedarg1mRNA and Arginase-1 protein production. Moreover, the transcription of genes that are typically upregulated in M2-polarized macrophages, such asym1, mcr2 and mgl2,was also decreased in peritoneal macrophages and IL-4-stimulatedTβRII-/-BMDMs. We found that cell surface and mRNA expression of Galectin-3, which also regulates M2 macrophage polarization, was lower inTβRII-/-BMDMs. Very interestingly, the impaired ability of these null mutant BMDMs to differentiate into IL-4 polarized macrophages was Stat6- and Smad3-independent, but correlated with reduced levels of phospho-Akt and β-catenin.

Conclusions

Our results establish a novel biological role for TGFβ signaling in controlling expression of genes characteristic for alternatively activated macrophages. We speculate that lack of TβRII signaling reduces the anti-inflammatory M2 phenotype of macrophages because of reduced expression of these products. This would cause defects in the ability of the M2 macrophages to negatively regulate other immune cells such as T-cells in the lung, possibly explaining the systemic inflammation observed inVav1-Cre x TβRIIfx/fxmice.
Interaction of C/EBP-beta and NF-Y factors constrains activity levels of the nutritionally controlled promoter IA expressing the acetyl-CoA carboxylase-alpha gene in cattle
Authors: Shi Xuanming , Metges Cornelia C , Seyfert Hans-Martin
Published: June 2012

Background

The enzyme acetyl-CoA carboxylase-alpha (ACC-α) is rate limiting for de novo fatty acid synthesis. Among the four promoters expressing the bovine gene, promoter IA (PIA) is dominantly active in lipogenic tissues. This promoter is in principal repressed but activated under favorable nutritional conditions. Previous analyses already coarsely delineated the repressive elements on the distal promoter but did not resolve the molecular nature of the repressor. Knowledge about the molecular functioning of this repressor is fundamental to understanding the nutrition mediated regulation of PIA activity. We analyzed here the molecular mechanism calibrating PIA activity.

Results

We finely mapped the repressor binding sites in reporter gene assays and demonstrate together with Electrophoretic Mobility Shift Assays that nuclear factor-Y (NF-Y) and CCAAT/enhancer binding protein-β(C/EBPβ) each separately repress PIA activity by binding to their cognate low affinity sites, located on distal elements of the promoter. Simultaneous binding of both factors results in strongest repression. Paradoxically, over expression of NFY factors, but also - and even more so - of C/EBPβ significantly activated the promoter when bound to high affinity sites on the proximal promoter. However, co-transfection experiments revealed that NF-Y may eventually diminish the strong stimulatory effect of C/EBPβ at the proximal PIA in a dose dependent fashion. We validated by chromatin immunoprecipitation, that NF-Y and C/EBP factors may physically interact.

Conclusion

The proximal promoter segment of PIA appears to be principally in an active state, since even minute concentrations of both, NF-Y and C/EBPβ factors can saturate the high affinity activator sites. Higher factor concentrations will saturate the low affinity repressive sites on the distal promoter resulting in reduced and calibrated promoter activity. Based on measurements of the mRNA concentrations of those factors in different tissues we propose that the interplay of both factors may set tissue-specific limits for PIA activity.
Modulations of neural activity in auditory streaming caused by spectral and temporal alternation in subsequent stimuli: a magnetoencephalographic study
Authors: Chakalov Ivan , Draganova Rossitza , Wollbrink Andreas , Preissl Hubert , Pantev Christo
Published: June 2012

Background

The aim of the present study was to identify a specific neuronal correlate underlying the pre-attentive auditory stream segregation of subsequent sound patterns alternating in spectral or temporal cues. Fifteen participants with normal hearing were presented with series’ of two consecutive ABA auditory tone-triplet sequences, the initial triplets being the Adaptation sequence and the subsequent triplets being the Test sequence. In the first experiment, the frequency separation (delta-f) between A and B tones in the sequences was varied by 2, 4 and 10 semitones. In the second experiment, a constant delta-f of 6 semitones was maintained but the Inter-Stimulus Intervals (ISIs) between A and B tones were varied. Auditory evoked magnetic fields (AEFs) were recorded using magnetoencephalography (MEG). Participants watched a muted video of their choice and ignored the auditory stimuli. In a subsequent behavioral study both MEG experiments were replicated to provide information about the participants’ perceptual state.

Results

MEG measurements showed a significant increase in the amplitude of the B-tone related P1 component of the AEFs as delta-f increased. This effect was seen predominantly in the left hemisphere. A significant increase in the amplitude of the N1 component was only obtained for a Test sequence delta-f of 10 semitones with a prior Adaptation sequence of 2 semitones. This effect was more pronounced in the right hemisphere. The additional behavioral data indicated an increased probability of two-stream perception for delta-f = 4 and delta-f = 10 semitones with a preceding Adaptation sequence of 2 semitones. However, neither the neural activity nor the perception of the successive streaming sequences were modulated when the ISIs were alternated.

Conclusions

Our MEG experiment demonstrated differences in the behavior of P1 and N1 components during the automatic segregation of sounds when induced by an initial Adaptation sequence. The P1 component appeared enhanced in all Test-conditions and thus demonstrates the preceding context effect, whereas N1 was specifically modulated only by large delta-f Test sequences induced by a preceding small delta-f Adaptation sequence. These results suggest that P1 and N1 components represent at least partially-different systems that underlie the neural representation of auditory streaming.
Genome-wide identification of differentially expressed genes under water deficit stress in upland cotton (Gossypium hirsutum L.)
Authors: Park Wonkeun , Scheffler Brian E , Bauer Philip J , Campbell B Todd
Published: June 2012

Background

Cotton is the world’s primary fiber crop and is a major agricultural commodity in over 30 countries. Like many other global commodities, sustainable cotton production is challenged by restricted natural resources. In response to the anticipated increase of agricultural water demand, a major research direction involves developing crops that use less water or that use water more efficiently. In this study, our objective was to identify differentially expressed genes in response to water deficit stress in cotton. A global expression analysis using cDNA-Amplified Fragment Length Polymorphism was conducted to compare root and leaf gene expression profiles from a putative drought resistant cotton cultivar grown under water deficit stressed and well watered field conditions.

Results

We identified a total of 519 differentially expressed transcript derived fragments. Of these, 147 transcript derived fragment sequences were functionally annotated according to their gene ontology. Nearly 70 percent of transcript derived fragments belonged to four major categories: 1) unclassified, 2) stress/defense, 3) metabolism, and 4) gene regulation. We found heat shock protein-related and reactive oxygen species-related transcript derived fragments to be among the major parts of functional pathways induced by water deficit stress. Also, twelve novel transcripts were identified as both water deficit responsive and cotton specific. A subset of differentially expressed transcript derived fragments was verified using reverse transcription-polymerase chain reaction. Differential expression analysis also identified five pairs of duplicated transcript derived fragments in which four pairs responded differentially between each of their two homologues under water deficit stress.

Conclusions

In this study, we detected differentially expressed transcript derived fragments from water deficit stressed root and leaf tissues in tetraploid cotton and provided their gene ontology, functional/biological distribution, and possible roles of gene duplication. This discovery demonstrates complex mechanisms involved with polyploid cotton’s transcriptome response to naturally occurring field water deficit stress. The genes identified in this study will provide candidate targets to manipulate the water use characteristics of cotton at the molecular level.
Capsule colonoscopy increases uptake of colorectal cancer screening
Authors: Groth Stefan , Krause Horst , Behrendt Rainer , Hill Helge , Börner Michael , Bastürk Murat , Plathner Nora , Schütte Friedrich , Gauger Ulrich , Riemann Jürgen Ferdinand , Altenhofen Lutz , Rösch Thomas
Published: June 2012

Background

Screening colonoscopy effectiveness is hampered by limited adherence by the general population. The present prospective study was performed to evaluate whether adding capsule colonoscopy to the endoscopic screening options increases uptake.

Methods

Invitation letters were sent to 2150 persons above the age of 55 insured with a German medical insurance company in the area of Rinteln, Lower Saxony with a baseline spontaneous annual screening colonoscopy uptake of 1 %. Both capsule or conventional colonoscopy were offered. Interested persons were given information about the two screening options by four local gastroenterologists and examinations were then performed according to screenees’ final choice.

Results

154 persons sought further information, and 34 and 90 underwent conventional and capsule colonoscopy, respectively. Colonoscopy uptake was thus increased by the invitation process by 60 % (1.6 % vs. 1 %; p = 0.075), while the option of capsule endoscopy led to a fourfold increase of screening uptake (4.2 % vs. 1 %, p < 0.001). Despite similar age distribution in both sex groups, uptake in men was significantly higher (5.6 % vs. 2.8 %, p = 002). However, overall adenoma yield was not different in both groups.

Conclusions

The present study suggests that offering the option of capsule colonoscopy increases uptake of endoscopic colorectal cancer screening. However, capsule endoscopy sensitivity for adenoma detection needs to be improved.