bluuebunny/crossref_metadata_2025 huggingface dataset:
Personal Meaning Orientations and Psychosocial Adaptation in Older Adults
Authors: Reker Gary T. , Woo Louis C.
Published: April 2011

This study examined how different patterns of sources of meaning in life impact the psychosocial adaptation of older adults. A total of 120 (62 women and 58 men) community-residing older adults completed self-report measures of sources of meaning in life, physical health, life satisfaction, depression, personality, existential regrets, attitudes toward aging, and attitudes toward life. Cluster analysis of sources of meaning revealed four distinct meaning orientations: self-transcendent ( n = 32), collectivistic ( n = 24), individualistic ( n = 34), and self-preoccupied ( n = 30). MANCOVA analysis of the four groups, controlling for age, marital status, education, and financial satisfaction, revealed a strong multivariate main effect for meaning orientation. No statistically significant gender and Gender × Meaning orientation interaction effects were found. Older adults, who derive meaning from self-transcendent sources, are more extraverted, open to experience, agreeable, and conscientious; perceive greater purpose and coherence in life; feel more in control in directing their lives; express a stronger desire to get more out of life; and are less depressed compared with those who derive meaning through pursuing self-serving interests without any real commitment to personal, interpersonal, or societal development. The implications of the findings for positive aging are discussed.
Intangible Heritage of Standard English Learners
Authors: Okoye-Johnson Ogo
Published: April 2011

Standard English Learners (SELs) are ethnic minority native speakers of English whose mastery of the “standard English language” used in the curriculum of schools is limited due to their use of ethnic-specific nonstandard dialect. Research in language development highlights language as a tool that allows the individual access to basic civil rights and opportunities in the area of politics, economics, and education. A correlation exists between proficiency in the use of Standard English and academic achievement, thereby highlighting the importance of validating the intangible language heritage that these students bring to the school environment while they are schooled in the use of Standard English.
Designing for Explanation in Health Care Applications of Expert Systems
Authors: Darlington Keith W.
Published: April 2011

A great deal has been written about the role of clinical decision support systems in medicine in recent years—an important category of which are expert systems. Expert systems would normally contain an explanation module—the subject of a great deal of research interest in the 1980s when the main problem-solving task for medical expert systems was diagnostics. However, expert systems nowadays are more likely to perform tasks other than diagnosis, yet the role of explanation in expert systems has been largely ignored in the health care literature since this time. Furthermore, user requirements can vary considerably in the health care domain and may include physicians, medical researchers, administrators, and patients. Such user groups would have differing levels of knowledge and goals, which would impact on the type of explanatory support provided by the system. This article examines the potential benefits of explanation facilities for a range of clinical tasks and also considers the ways in which explanation facilities may be delivered so as to be of benefit to these categories of health care user for these tasks.
Hospitalization for pain in patients with sickle cell disease treated with sildenafil for elevated TRV and low exercise capacity
Authors: Machado Roberto F. , Barst Robyn J. , Yovetich Nancy A. , Hassell Kathryn L. , Kato Gregory J. , Gordeuk Victor R. , Gibbs J. Simon R. , Little Jane A. , Schraufnagel Dean E. , Krishnamurti Lakshmanan , Girgis Reda E. , Morris Claudia R. , Rosenzweig Erika B. , Badesch David B. , Lanzkron Sophie , Onyekwere Onyinye , Castro Oswaldo L. , Sachdev Vandana , Waclawiw Myron A. , Woolson Rob , Goldsmith Jonathan C. , Gladwin Mark T. ,   on behalf of the walk-PHaSST Investigators and Patients
Published: April 2011

In adults with sickle cell disease (SCD), an increased tricuspid regurgitation velocity (TRV) by Doppler echocardiography is associated with increased morbidity and mortality. Although sildenafil has been shown to improve exercise capacity in patients with pulmonary arterial hypertension, it has not been evaluated in SCD. We therefore sought to determine whether sildenafil could improve exercise capacity in SCD patients with increased TRV and a low exercise capacity. A TRV ≥ 2.7 m/s and a 6-minute walk distance (6MWD) between 150 and 500 m were required for enrollment in this 16-week, double-blind, placebo-controlled sildenafil trial. After 74 of the screened subjects were randomized, the study was stopped early due to a higher percentage of subjects experiencing serious adverse events in the sildenafil arm (45% of sildenafil, 22% of placebo, P = .022). Subject hospitalization for pain was the predominant cause for this difference: 35% with sildenafil compared with 14% with placebo (P = .029). There was no evidence of a treatment effect on 6MWD (placebo-corrected effect −9 m; 95% confidence interval [95% CI] −56-38; P = .703), TRV (P = .503), or N-terminal pro-brain natriuretic peptide (P = .410). Sildenafil appeared to increase hospitalization rates for pain in patients with SCD. This study is registered at www.clinicaltrials.gov as NCT00492531.
SNP array–based karyotyping: differences and similarities between aplastic anemia and hypocellular myelodysplastic syndromes
Authors: Afable Manuel G. , Wlodarski Marcin , Makishima Hideki , Shaik Mohammed , Sekeres Mikkael A. , Tiu Ramon V. , Kalaycio Matt , O'Keefe Christine L. , Maciejewski Jaroslaw P.
Published: April 2011

In aplastic anemia (AA), contraction of the stem cell pool may result in oligoclonality, while in myelodysplastic syndromes (MDS) a single hematopoietic clone often characterized by chromosomal aberrations expands and outcompetes normal stem cells. We analyzed patients with AA (N = 93) and hypocellular MDS (hMDS, N = 24) using single nucleotide polymorphism arrays (SNP-A) complementing routine cytogenetics. We hypothesized that clinically important cryptic clonal aberrations may exist in some patients with BM failure. Combined metaphase and SNP-A karyotyping improved detection of chromosomal lesions: 19% and 54% of AA and hMDS cases harbored clonal abnormalities including copy-neutral loss of heterozygosity (UPD, 7%). Remarkably, lesions involving the HLA locus suggestive of clonal immune escape were found in 3 of 93 patients with AA. In hMDS, additional clonal lesions were detected in 5 (36%) of 14 patients with normal/noninformative routine cytogenetics. In a subset of AA patients studied at presentation, persistent chromosomal genomic lesions were found in 10 of 33, suggesting that the initial diagnosis may have been hMDS. Similarly, using SNP-A, earlier clonal evolution was found in 4 of 7 AA patients followed serially. In sum, our results indicate that SNP-A identify cryptic clonal genomic aberrations in AA and hMDS leading to improved distinction of these disease entities.
Genomic characterization implicates iAMP21 as a likely primary genetic event in childhood B-cell precursor acute lymphoblastic leukemia
Authors: Rand Vikki , Parker Helen , Russell Lisa J. , Schwab Claire , Ensor Hannah , Irving Julie , Jones Lisa , Masic Dino , Minto Lynne , Morrison Heather , Ryan Sarra , Robinson Hazel , Sinclair Paul , Moorman Anthony V. , Strefford Jonathan C. , Harrison Christine J.
Published: April 2011

Intrachromosomal amplification of chromosome 21 (iAMP21) defines a distinct subgroup of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) that has a dismal outcome when treated with standard therapy. For improved diagnosis and risk stratification, the initiating genetic events need to be elucidated. To investigate the genetic basis of BCP-ALL, genomes of 94 iAMP21 patients were interrogated by arrays, FISH, and multiplex ligation-dependent probe amplification. Most copy number alterations targeted chromosome 21, reinforcing the complexity of this chromosome. The common region of amplification on chromosome 21 was refined to a 5.1-mb region that included RUNX1, miR-802, and genes mapping to the Down syndrome critical region. Recurrent abnormalities affecting genes in key pathways were identified: IKZF1 (22%), CDKN2A/B (17%), PAX5 (8%), ETV6 (19%), and RB1 (37%). Investigation of clonal architecture provided evidence that these abnormalities, and P2RY8-CRLF2, were secondary to chromosome 21 rearrangements. Patient outcome was uniformly poor with standard therapy irrespective of the presence or absence of these changes. This study has provided evidence that chromosome 21 instability is the only anomaly among those so far investigated that is common to all iAMP21 patients, and therefore the initiating event is likely to be found among the complex structural rearrangements of this abnormal chromosome.
Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts
Authors: Brunstein Claudio G. , Fuchs Ephraim J. , Carter Shelly L. , Karanes Chatchada , Costa Luciano J. , Wu Juan , Devine Steven M. , Wingard John R. , Aljitawi Omar S. , Cutler Corey S. , Jagasia Madan H. , Ballen Karen K. , Eapen Mary , O'Donnell Paul V. ,   on behalf of the Blood and Marrow Transplant Clinical Trials Network
Published: April 2011

The Blood and Marrow Transplant Clinical Trials Network conducted 2 parallel multicenter phase 2 trials for individuals with leukemia or lymphoma and no suitable related donor. Reduced intensity conditioning (RIC) was used with either unrelated double umbilical cord blood (dUCB) or HLA-haploidentical related donor bone marrow (Haplo-marrow) transplantation. For both trials, the transplantation conditioning regimen incorporated cyclophosphamide, fludarabine, and 200 cGy of total body irradiation. The 1-year probabilities of overall and progression-free survival were 54% and 46%, respectively, after dUCB transplantation (n = 50) and 62% and 48%, respectively, after Haplo-marrow transplantation (n = 50). The day +56 cumulative incidence of neutrophil recovery was 94% after dUCB and 96% after Haplo-marrow transplantation. The 100-day cumulative incidence of grade II-IV acute GVHD was 40% after dUCB and 32% after Haplo-marrow transplantation. The 1-year cumulative incidences of nonrelapse mortality and relapse after dUCB transplantation were 24% and 31%, respectively, with corresponding results of 7% and 45%, respectively, after Haplo-marrow transplantation. These multicenter studies confirm the utility of dUCB and Haplo-marrow as alternative donor sources and set the stage for a multicenter randomized clinical trial to assess the relative efficacy of these 2 strategies. The trials are registered at www.clinicaltrials.gov under NCT00864227 (BMT CTN 0604) and NCT00849147 (BMT CTN 0603).
Transcriptomic analysis of milk somatic cells in mastitis resistant and susceptible sheep upon challenge with Staphylococcus epidermidis and Staphylococcus aureus
Authors: Bonnefont Cécile MD , Toufeer Mehdi , Caubet Cécile , Foulon Eliane , Tasca Christian , Aurel Marie-Rose , Bergonier Dominique , Boullier Séverine , Robert-Granié Christèle , Foucras Gilles , Rupp Rachel
Published: April 2011

Background

The existence of a genetic basis for host responses to bacterial intramammary infections has been widely documented, but the underlying mechanisms and the genes are still largely unknown. Previously, two divergent lines of sheep selected for high/low milk somatic cell scores have been shown to be respectively susceptible and resistant to intramammary infections by Staphylococcus spp. Transcriptional profiling with an 15K ovine-specific microarray of the milk somatic cells of susceptible and resistant sheep infected successively by S. epidermidis and S. aureus was performed in order to enhance our understanding of the molecular and cellular events associated with mastitis resistance.

Results

The bacteriological titre was lower in the resistant than in the susceptible animals in the 48 hours following inoculation, although milk somatic cell concentration was similar. Gene expression was analysed in milk somatic cells, mainly represented by neutrophils, collected 12 hours post-challenge. A high number of differentially expressed genes between the two challenges indicated that more T cells are recruited upon inoculation by S. aureus than S. epidermidis. A total of 52 genes were significantly differentially expressed between the resistant and susceptible animals. Further Gene Ontology analysis indicated that differentially expressed genes were associated with immune and inflammatory responses, leukocyte adhesion, cell migration, and signal transduction. Close biological relationships could be established between most genes using gene network analysis. Furthermore, gene expression suggests that the cell turn-over, as a consequence of apoptosis/granulopoiesis, may be enhanced in the resistant line when compared to the susceptible line.

Conclusions

Gene profiling in resistant and susceptible lines has provided good candidates for mapping the biological pathways and genes underlying genetically determined resistance and susceptibility towards Staphylococcus infections, and opens new fields for further investigation.
Identification and characterization of plant Haspin kinase as a histone H3 threonine kinase
Authors: Kurihara Daisuke , Matsunaga Sachihiro , Omura Tomohiro , Higashiyama Tetsuya , Fukui Kiichi
Published: April 2011

Background

Haspin kinases are mitotic kinases that are well-conserved from yeast to human. Human Haspin is a histone H3 Thr3 kinase that has important roles in chromosome cohesion during mitosis. Moreover, phosphorylation of histone H3 at Thr3 by Haspin in fission yeast, Xenopus, and human is required for accumulation of Aurora B on the centromere, and the subsequent activation of Aurora B kinase activity for accurate chromosome alignment and segregation. Although extensive analyses of Haspin have been carried out in yeast and animals, the function of Haspin in organogenesis remains unclear.

Results

Here, we identified a Haspin kinase, designated AtHaspin, in Arabidopsis thaliana. The purified AtHaspin phosphorylated histone H3 at both Thr3 and Thr11 in vitro. Live imaging of AtHaspin-tdTomato and GFP-α-tubulin in BY-2 cells showed that AtHaspin-tdTomato localized on chromosomes during prometaphase and metaphase, and around the cell plate during cytokinesis. This localization of AtHaspin overlapped with that of phosphorylated Thr3 and Thr11 of histone H3 in BY-2 cells. AtHaspin-GFP driven by the native promoter was expressed in root meristems, shoot meristems, floral meristems, and throughout the whole embryo at stages of high cell division. Overexpression of a kinase domain mutant of AtHaspin decreased the size of the root meristem, which delayed root growth.

Conclusions

Our results indicated that the Haspin kinase is a histone H3 threonine kinase in A. thaliana. AtHaspin phosphorylated histone H3 at both Thr3 and Thr11 in vitro. The expression and dominant-negative analysis showed that AtHaspin may have a role in mitotic cell division during plant growth. Further analysis of coordinated mechanisms involving Haspin and Aurora kinases will shed new light on the regulation of chromosome segregation in cell division during plant growth and development.
New adipokines vaspin and omentin. Circulating levels and gene expression in adipose tissue from morbidly obese women
Authors: Auguet Teresa , Quintero Yunuen , Riesco David , Morancho Beatriz , Terra Ximena , Crescenti Anna , Broch Montserrat , Aguilar Carmen , Olona Montserrat , Porras José Antonio , Hernandez Mercè , Sabench Fátima , del Castillo Daniel , Richart Cristóbal
Published: April 2011

Background

Vaspin and omentin are recently described molecules that belong to the adipokine family and seem to be related to metabolic risk factors. The objectives of this study were twofold: to evaluate vaspin and omentin circulating levels and mRNA expression in subcutaneous and visceral adipose tissues in non-diabetic morbidly obese women; and to assess the relationship of vaspin and omentin with anthropometric and metabolic parameters, and other adipo/cytokines.

Design

We analysed vaspin and omentin circulating levels in 71 women of European descent (40 morbidly obese [BMI ≥ 40 kg/m2] and 31 lean [BMI ≤ 25]). We assessed vaspin and omentin gene expression in paired samples of visceral and subcutaneous abdominal adipose tissue from 46 women: 40 morbidly obese and 6 lean. We determined serum vaspin and plasma omentin levels with an Enzyme-Linked Immunosorbent Assay and adipose tissue mRNA expression by real time RT-PCR.

Results

Serum vaspin levels in the morbidly obese were not significantly different from those in controls. They correlated inversely with levels of lipocalin 2 and interleukin 6. Vaspin mRNA expression was significantly higher in the morbidly obese, in both subcutaneous and visceral adipose tissue.

Plasma omentin levels were significantly lower in the morbidly obese and they correlated inversely with glucidic metabolism parameters. Omentin circulating levels, then, correlated inversely with the metabolic syndrome (MS). Omentin expression in visceral adipose tissue was significantly lower in morbidly obese women than in controls.

Conclusions

The present study indicates that vaspin may have a compensatory role in the underlying inflammation of obesity. Decreased omentin circulating levels have a close association with MS in morbidly obese women.
Validation of the post sleep questionnaire for assessing subjects with restless legs syndrome: results from two double-blind, multicenter, placebo-controlled clinical trials
Authors: Canafax Daniel M , Bhanegaonkar Abhijeet , Bharmal Murtuza , Calloway Michael
Published: April 2011

Background

Because of the subjective nature of Restless Legs Syndrome (RLS) symptoms and the impact of these symptoms on sleep, patient-reported outcomes (PROs) play a prominent role as study endpoints in clinical trials investigating RLS treatments. The objective of this study was to validate a new measure, the Post Sleep Questionnaire (PSQ), to assess sleep dysfunction in subjects with moderate-to-severe RLS symptoms.

Methods

Pooled data were analyzed from two 12-week, randomized, placebo-controlled trials of gabapentin enacarbil (N = 540). At baseline and Week 12, subjects completed the PSQ and other validated health surveys: IRLS Rating Scale, Clinical Global Impression of Improvement (CGI-I), Profile of Mood States (POMS), Medical Outcomes Study Scale-Sleep (MOS-Sleep), and RLS-Quality of Life (RLSQoL). Pooled data were usedpost hocto examine the convergent, divergent, known-group validity and the responsiveness of the PSQ.

Results

Convergent validity was demonstrated by significant correlations between baseline PSQ items and total scores of IRLS, POMS, RLSQoL, and the MOS-Sleep Scale (p ≤ 0.007 each). Divergent validity was demonstrated through the lack of significant correlations between PSQ items and demographic characteristics. Correlations (p < 0.0001) between RLS severity groups and PSQ items demonstrated known-group validity. Mean changes in investigator- and subject-rated CGI-I scores for each PSQ item (p < 0.0001) demonstrated the PSQ's responsiveness to patient change as reported by their care provider.

Conclusions

Although these analyses were potentially limited by the use of clinical trial data and not prospective data from a study conducted solely for validation purposes, the PSQ demonstrated robust psychometric properties and is a valid instrument for assessing sleep and sleep improvements in subjects with moderate-to-severe RLS symptoms.

Trial Registration

This study analyzed data from two registered trials,NCT00298623andNCT00365352.
Echium acanthocarpum hairy root cultures, a suitable system for polyunsaturated fatty acid studies and production
Authors: Cequier-Sánchez Elena , Rodríguez Covadonga , Dorta-Guerra Roberto , Ravelo Ángel G , Zárate Rafael
Published: April 2011

Background

The therapeutic and health promoting role of highly unsaturated fatty acids (HUFAs) from fish, i.e. eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) are well known. These same benefits may however be shared by some of their precursors, the polyunsaturated fatty acids (PUFAs), such as stearidonic acid (SDA, 18:4 n-3). In order to obtain alternative sources for the large-scale production of PUFAs, new searches are being conducted focusing on higher plants oils which can contain these n-3 and n-6 C18 precursors, i.e. SDA and GLA (18:3n-6, γ-linolenic acid).

Results

The establishment of the novel Echium acanthocarpum hairy root cultures represents a powerful tool in order to research the accumulation and metabolism of fatty acids (FAs) in a plant particularly rich in GLA and SDA. Furthermore, this study constitutes the first example of a Boraginaceae species hairy root induction and establishment for FA studies and production. The dominant PUFAs, 18:2n-6 (LA, linoleic acid) and 18:3n-6 (GLA), accounted for about 50% of total FAs obtained, while the n-3 PUFAs, 18:3n-3 (ALA, α-linolenic acid) and 18:4n-3 (SDA), represented approximately 5% of the total. Production of FAs did not parallel hairy root growth, and the optimal productivity was always associated with the highest biomass density during the culture period. Assuming a compromise between FA production and hairy root biomass, it was determined that sampling times 4 and 5 gave the most useful FA yields. Total lipid amounts were in general comparable between the different hairy root lines (29.75 and 60.95 mg/g DW), with the major lipid classes being triacylglycerols. The FAs were chiefly stored in the hairy roots with very minute amounts being released into the liquid nutrient medium.

Conclusions

The novel results presented here show the utility and high potential of E. acanthocarpum hairy roots. They are capable of biosynthesizing and accumulating a large range of polyunsaturated FAs, including the target GLA and SDA fatty acids in appreciable quantities.
Rectal gel application of Withania somnifera root extract expounds anti-inflammatory and muco-restorative activity in TNBS-induced Inflammatory Bowel Disease
Authors: Pawar Pankaj , Gilda Suhit , Sharma Siddhesh , Jagtap Suresh , Paradkar Anant , Mahadik Kakasaheb , Ranjekar Prabhakar , Harsulkar Abhay
Published: April 2011

Background

Inflammatory Bowel Disease (IBD) is marked with chronic inflammation of intestinal epithelium driven by oxidative stress. Traditional treatments with plant extracts gained renewed interest due to their ability to ameliorate the multi factorial conditions like inflammation. We investigated the beneficial effects ofWithania somniferain Trinitro Benzyl Sulfonic Acid (TNBS) induced experimental IBD through a rectally applicable formulation.

Methods

The study included (i) preparation of gel formulation from aqueousWithania somniferaroot extract (WSRE), (ii) biochemical assays to determine its performance potential, (iii) testing of formulation efficacy in TNBS-induced IBD rat model, and (iv) histo-patholgical studies to assess its healing and muco-regenerative effect in IBD-induced rats. For this purpose, concentration dependant antioxidant activity of the extracts were evaluated using biochemical assays like (a) inhibition of lipid peroxidation, (b) NO scavenging, (c) H2O2scavenging, and (d) ferric reducing power assay.

Results

The extract, at 500 μg/ml, the highest concentration tested, showed 95.6% inhibition of lipid peroxidation, 14.8% NO scavenging, 81.79% H2O2scavenging and a reducing capacity of 0.80. The results were comparable with standard antioxidants, ascorbic acid and curcumin. WSRE treatment positively scored on histopathological parameters like necrosis, edema, neutrophil infiltration. The post treatment intestinal features showed restoration at par with the healthy intestine. In view of these results, gel formulation containing an aqueous extract ofW. somnifera, prepared for rectal application was tested for its anti-inflammatory activity in TNBS-induced rat models for IBD. Commercially available anti-inflammatory drug Mesalamine was used as the standard in this assay.

Conclusions

Dose of the rectal gel applied at 1000 mg of WSRE per kg rat weight showed significant muco-restorative efficacy in the IBD-induced rats, validated by histo-pathological studies.
Innate immunity and monocyte-macrophage activation in atherosclerosis
Authors: Shalhoub Joseph , Falck-Hansen Mika A , Davies Alun H , Monaco Claudia
Published: April 2011

Innate inflammation is a hallmark of both experimental and human atherosclerosis. The predominant innate immune cell in the atherosclerotic plaque is the monocyte-macrophage. The behaviour of this cell type within the plaque is heterogeneous and depends on the recruitment of diverse monocyte subsets. Furthermore, the plaque microenvironment offers polarisation and activation signals which impact on phenotype. Microenvironmental signals are sensed through pattern recognition receptors, including toll-like and NOD-like receptors thus dictating macrophage behaviour and outcome in atherosclerosis. Recently cholesterol crystals and modified lipoproteins have been recognised as able to directly engage these pattern recognition receptors. The convergent role of such pathways in terms of macrophage activation is discussed in this review.
A compact model for magnetic tunnel junction (MTJ) switched by thermally assisted Spin transfer torque (TAS + STT)
Authors: Zhao Weisheng , Duval Julien , Klein Jacques-Olivier , Chappert Claude
Published: April 2011

Thermally assisted spin transfer torque [TAS + STT] is a new switching approach for magnetic tunnel junction [MTJ] nanopillars that represents the best trade-off between data reliability, power efficiency and density. In this paper, we present a compact model for MTJ switched by this approach, which integrates a number of physical models such as temperature evaluation and STT dynamic switching models. Many experimental parameters are included directly to improve the simulation accuracy. It is programmed in the Verilog-A language and compatible with the standard IC CAD tools, providing an easy parameter configuration interface and allowing high-speed co-simulation of hybrid MTJ/CMOS circuits.
Butterfly eyespot serial homology: enter the Hox genes
Authors: Hombría James Castelli-Gair
Published: April 2011

Hox genes modify serial homology patterns in many organisms, exemplified in vertebrates by modification of the axial skeleton and in arthropods by diversification of the body segments. Butterfly wing eyespots also appear in a serial homologous pattern that, in certain species, is subject to local modification. A paper in EvoDevo reports the Hox gene Antp is the earliest known gene to have eyespot-specific expression; however, not all Lepidoptera express Antp in eyespots, suggesting some developmental flexibility.

See research article: http://www.evodevojournal.com/content/2/1/9
Expression of constitutively active erythropoietin receptor in pyramidal neurons of cortex and hippocampus boosts higher cognitive functions in mice
Authors: Sargin Derya , El-Kordi Ahmed , Agarwal Amit , Müller Michael , Wojcik Sonja M , Hassouna Imam , Sperling Swetlana , Nave Klaus-Armin , Ehrenreich Hannelore
Published: April 2011

Background

Erythropoietin (EPO) and its receptor (EPOR) are expressed in the developing brain and their transcription is upregulated in adult neurons and glia upon injury or neurodegeneration. We have shown neuroprotective effects and improved cognition in patients with neuropsychiatric diseases treated with EPO. However, the critical EPO targets in brain are unknown, and separation of direct and indirect effects has remained difficult, given the role of EPO in hematopoiesis and brain oxygen supply.

Results

Here we demonstrate that mice with transgenic expression of a constitutively active EPOR isoform (cEPOR) in pyramidal neurons of cortex and hippocampus exhibit enhancement of spatial learning, cognitive flexibility, social memory, and attentional capacities, accompanied by increased impulsivity. Superior cognitive performance is associated with augmented long-term potentiation of cEPOR expressing neurons in hippocampal slices.

Conclusions

Active EPOR stimulates neuronal plasticity independent of any hematopoietic effects and in addition to its neuroprotective actions. This property of EPOR signaling should be exploited for defining novel strategies to therapeutically enhance cognitive performance in disease conditions.
Effects of in ovo electroporation on endogenous gene expression: genome-wide analysis
Authors: Farley Emma K , Gale Emily , Chambers David , Li Meng
Published: April 2011

Background

In ovo electroporation is a widely used technique to study gene function in developmental biology. Despite the widespread acceptance of this technique, no genome-wide analysis of the effects of in ovo electroporation, principally the current applied across the tissue and exogenous vector DNA introduced, on endogenous gene expression has been undertaken. Here, the effects of electric current and expression of a GFP- containing construct, via electroporation into the midbrain of Hamburger-Hamilton stage 10 chicken embryos, are analysed by microarray.

Results

Both current alone and in combination with exogenous DNA expression have a small but reproducible effect on endogenous gene expression, changing the expression of the genes represented on the array by less than 0.1% (current) and less than 0.5% (current + DNA), respectively. The subset of genes regulated by electric current and exogenous DNA span a disparate set of cellular functions. However, no genes involved in the regional identity were affected. In sharp contrast to this, electroporation of a known transcription factor, Dmrt5, caused a much greater change in gene expression.

Conclusions

These findings represent the first systematic genome-wide analysis of the effects of in ovo electroporation on gene expression during embryonic development. The analysis reveals that this process has minimal impact on the genetic basis of cell fate specification. Thus, the study demonstrates the validity of the in ovo electroporation technique to study gene function and expression during development. Furthermore, the data presented here can be used as a resource to refine the set of transcriptional responders in future in ovo electroporation studies of specific gene function.
Seroprevalence of Human herpesvirus 8 (HHV-8) and incidence of Kaposi's sarcoma in Iran
Authors: Jalilvand Somayeh , Shoja Zabihollah , Mokhtari-Azad Talat , Nategh Rakhshandeh , Gharehbaghian Ahmad
Published: April 2011

Seroepidemiological surveys show that the prevalence of human herpesvirus 8 (HHV-8) infection mostly varies in various geographical areas and reflects the local incidence of classic and endemic KS, being widespread in sub-Saharan Africa and Mediterranean countries and uncommon in the USA and Northern Europe. In the Middle East only few populations, such as Ashkenazi and Sephardic groups in Israel, have been adequately evaluated for HHV-8 seroprevalence. Among Iranian population a striking higher seroprevalence of HHV8 has been reported among haemodialysis (16.9%), renal transplant recipients (25%) and HIV (45.7%) patients compared to blood donors (2%). Kaposi's sarcoma (KS) is the rarest cancer in Iran, with an annual age-standardized incidence varying from 0.10 to 0.17 per 100,000 in males and from 0.06 to 0.08 per 100,000 in females. KS, however, is one of the most important malignancies in Iranian renal transplanted patients affecting up to 2.4% of organ recipients. The epidemiology of HHV8 and KS in Iran needs further evaluation. While the high prevalence of HHV-8 antibodies in HIV positive and haemodialysis individuals may be attributed to high-risk sexual behavior and polytransfusions, respectively, unknown determinants may be responsible for high seroprevalence of HHV8 and high incidence of KS in solid organ recipients. A global survey on HHV8 seroprevalence in Iran is mandatory to define co-factors associated with HHV8 infection and KS risk in the general Iranian population and in specific patient groups.
IP6K gene identification in plant genomes by tag searching
Authors: Fassetti Fabio , Leone Ofelia , Palopoli Luigi , Rombo Simona E , Saiardi Adolfo
Published: April 2011

Background

Plants have played a special role in inositol polyphosphate (IP) research since in plant seeds was discovered the first IP, the fully phosphorylated inositol ring of phytic acid (IP6). It is now known that phytic acid is further metabolized by the IP6 Kinases (IP6Ks) to generate IP containing pyro-phosphate moiety. The IP6K are evolutionary conserved enzymes identified in several mammalian, fungi and amoebae species. Although IP6K has not yet been identified in plant chromosomes, there are many clues suggesting its presences in vegetal cells.

Results

In this paper we propose a new approach to search for the plant IP6K gene, that lead to the identification in plant genome of a nucleotide sequence corresponding to a specific tag of the IP6K family. Such a tag has been found in all IP6K genes identified up to now, as well as in all genes belonging to the Inositol Polyphosphate Kinases superfamily (IPK). The tag sequence corresponds to the inositol-binding site of the enzyme, and it can be considered as characterizing all IPK genes. To this aim we applied a technique based on motif discovery. We exploited DLSME, a software recently proposed, which allows for the motif structure to be only partially specified by the user. First we applied the new method on mitochondrial DNA (mtDNA) of plants, where such a gene could have been nested, possibly encrypted and hidden by virtue of the editing and/or trans-splicing processes. Then we looked for the gene in nuclear genome of two model plants, Arabidopsis thaliana and Oryza sativa.

Conclusions

The analysis we conducted in plant mitochondria provided the negative, though we argue relevant, result that IP6K does not actually occur in vegetable mtDNA. Very interestingly, the tag search in nuclear genomes lead us to identify a promising sequence in chromosome 5 of Oryza sativa. Further analyses are in course to confirm that this sequence actually corresponds to IP6K mammalian gene.
Mining the TRAF6/p62 interactome for a selective ubiquitination motif
Authors: Jadhav Trafina S , Wooten Marie W , Wooten Michael C
Published: April 2011

A new approach is described here to predict ubiquitinated substrates of the E3 ubiquitin ligase, TRAF6, which takes into account its interaction with the scaffold protein SQSTM1/p62. A novel TRAF6 ubiquitination motif defined as [–(hydrophobic)–k–(hydrophobic)–x–x–(hydrophobic)– (polar)–(hydrophobic)–(polar)–(hydrophobic)] was identified and used to screen the TRAF6/p62 interactome composed of 155 proteins, that were either TRAF6 or p62 interactors, or a negative dataset, composed of 54 proteins with no known association to either TRAF6 or p62. NRIF (K19), TrkA (K485), TrkB (K811), TrkC (K602 and K815), NTRK2 (K828), NTRK3 (K829) and MBP (K169) were found to possess a perfect match for the amino acid consensus motif for TRAF6/p62 ubiquitination. Subsequent analyses revealed that this motif was biased to the C-terminal regions of the protein (nearly 50% the sites), and had preference for loops (~50%) and helices (~37%) over beta-strands (15% or less). In addition, the motif was observed to be in regions that were highly solvent accessible (nearly 90%). Our findings suggest that specific Lysines may be selected for ubiquitination based upon an embedded code defined by a specific amino acid motif with structural determinants. Collectively, our results reveal an unappreciated role for the scaffold protein in targeting ubiquitination. The findings described herein could be used to aid in identification of other E3/scaffold ubiquitination sites.
Separation of blended data by iterative estimation and subtraction of blending interference noise
Authors: Mahdad Araz , Doulgeris Panagiotis , Blacquiere Gerrit
Published: April 2011

Seismic acquisition is a trade-off between economy and quality. In conventional acquisition the time intervals between successive records are large enough to avoid interference in time. To obtain an efficient survey, the spatial source sampling is therefore often (too) large. However, in blending, or simultaneous acquisition, temporal overlap between shot records is allowed. This additional degree of freedom in survey design significantly improves the quality or the economics or both. Deblending is the procedure of recovering the data as if they were acquired in the conventional, unblended way. A simple least-squares procedure, however, does not remove the interference due to other sources, or blending noise. Fortunately, the character of this noise is different in different domains, e.g., it is coherent in the common source domain, but incoherent in the common receiver domain. This property is used to obtain a considerable improvement. We propose to estimate the blending noise and subtract it from the blended data. The estimate does not need to be perfect because our procedure is iterative. Starting with the least-squares deblended data, the estimate of the blending noise is obtained via the following steps: sort the data to a domain where the blending noise is incoherent; apply a noise suppression filter; apply a threshold to remove the remaining noise, ending up with (part of) the signal; compute an estimate of the blending noise from this signal. At each iteration, the threshold can be lowered and more of the signal is recovered. Promising results were obtained with a simple implementation of this method for both impulsive and vibratory sources. Undoubtedly, in the future algorithms will be developed for the direct processing of blended data. However, currently a high-quality deblending procedure is an important step allowing the application of contemporary processing flows.
Application of the multiaxial perfectly matched layer (M-PML) to near-surface seismic modeling with Rayleigh waves
Authors: Zeng Chong , Xia Jianghai , Miller Richard D. , Tsoflias Georgios P.
Published: April 2011

Perfectly matched layer (PML) absorbing boundaries are widely used to suppress spurious edge reflections in seismic modeling. When modeling Rayleigh waves with the existence of the free surface, the classical PML algorithm becomes unstable when the Poisson’s ratio of the medium is high. Numerical errors can accumulate exponentially and terminate the simulation due to computational overflows. Numerical tests show that the divergence speed of the classical PML has a nonlinear relationship with the Poisson’s ratio. Generally, the higher the Poisson’s ratio, the faster the classical PML diverges. The multiaxial PML (M-PML) attenuates the waves in PMLs using different damping profiles that are proportional to each other in orthogonal directions. The proportion coefficients of the damping profiles usually vary with the specific model settings. If they are set appropriately, the M-PML algorithm is stable for high Poisson’s ratio earth models. Through numerical tests of 40 models with Poisson’s ratios that varied from 0.10 to 0.49, we found that a constant proportion coefficient of 1.0 for the x- and z-directional damping profiles is sufficient to stabilize the M-PML for all 2D isotropic elastic cases. Wavefield simulations indicate that the instability of the classical PML is strongly related to the wave phenomena near the free surface. When applying the multiaxial technique only in the corners of the PML near the free surface, the original M-PML technique can be simplified without losing its stability. The simplified M-PML works efficiently for homogeneous and heterogeneous earth models with high Poisson’s ratios. The analysis in this paper is based on 2D finite difference modeling in the time domain that can easily be extended into the 3D domain with other numerical methods.
3D induced-polarization data inversion for complex resistivity
Authors: Commer Michael , Newman Gregory A. , Williams Kenneth H. , Hubbard Susan S.
Published: April 2011

The conductive and capacitive material properties of the subsurface can be quantified through the frequency-dependent complex resistivity. However, the routine three-dimensional (3D) interpretation of voluminous induced polarization (IP) data sets still poses a challenge due to large computational demands and solution nonuniqueness. We have developed a flexible methodology for 3D (spectral) IP data inversion. Our inversion algorithm is adapted from a frequency-domain electromagnetic (EM) inversion method primarily developed for large-scale hydrocarbon and geothermal energy exploration purposes. The method has proven to be efficient by implementing the nonlinear conjugate gradient method with hierarchical parallelism and by using an optimal finite-difference forward modeling mesh design scheme. The method allows for a large range of survey scales, providing a tool for both exploration and environmental applications. We experimented with an image focusing technique to improve the poor depth resolution of surface data sets with small survey spreads. The algorithm’s underlying forward modeling operator properly accounts for EM coupling effects; thus, traditionally used EM coupling correction procedures are not needed. The methodology was applied to both synthetic and field data. We tested the benefit of directly inverting EM coupling contaminated data using a synthetic large-scale exploration data set. Afterward, we further tested the monitoring capability of our method by inverting time-lapse data from an environmental remediation experiment near Rifle, Colorado. Similar trends observed in both our solution and another 2D inversion were in accordance with previous findings about the IP effects due to subsurface microbial activity.
A compressed implicit Jacobian scheme for 3D electromagnetic data inversion
Authors: Li Maokun , Abubakar Aria , Liu Jianguo , Pan Guangdong , Habashy Tarek M.
Published: April 2011

We developed a compressed implicit Jacobian scheme for the regularized Gauss-Newton inversion algorithm for reconstructing 3D conductivity distributions from electromagnetic data. In this algorithm, the Jacobian matrix, whose storage usually requires a large amount of memory, is decomposed in terms of electric fields excited by sources located and oriented identically to the physical sources and receivers. As a result, the memory usage for the Jacobian matrix reduces from O(NFNSNRNP) to O[NF(NS + NR)NP], where NF is the number of frequencies, NS is the number of sources, NR is the number of receivers, and NP is the number of conductivity cells to be inverted. When solving the Gauss-Newton linear system of equations using iterative solvers, the multiplication of the Jacobian matrix with a vector is converted to matrix-vector operations between the matrices of the electric fields and the vector. In order to mitigate the additional computational overhead of this scheme, these fields are further compressed using the adaptive cross approximation (ACA) method. The compressed implicit Jacobian scheme provides a good balance between memory usage and computational time and renders the Gauss-Newton algorithm more efficient. We demonstrated the benefits of this scheme using numerical examples including both synthetic and field data for both crosswell and controlled-source electromagnetic (CSEM) applications.
Actin-Capping Protein and the Hippo pathway regulate F-actin and tissue growth in Drosophila
Authors: Fernández Beatriz García , Gaspar Pedro , Brás-Pereira Catarina , Jezowska Barbara , Rebelo Sofia Raquel , Janody Florence
Published: April 2011

The conserved Hippo tumor suppressor pathway is a key kinase cascade that controls tissue growth by regulating the nuclear import and activity of the transcription co-activator Yorkie. Here, we report that the actin-Capping Protein αβ heterodimer, which regulates actin polymerization, also functions to suppress inappropriate tissue growth by inhibiting Yorkie activity. Loss of Capping Protein activity results in abnormal accumulation of apical F-actin, reduced Hippo pathway activity and the ectopic expression of several Yorkie target genes that promote cell survival and proliferation. Reduction of two other actin-regulatory proteins, Cofilin and the cyclase-associated protein Capulet, cause abnormal F-actin accumulation, but only the loss of Capulet, like that of Capping Protein, induces ectopic Yorkie activity. Interestingly, F-actin also accumulates abnormally when Hippo pathway activity is reduced or abolished, independently of Yorkie activity, whereas overexpression of the Hippo pathway component expanded can partially reverse the abnormal accumulation of F-actin in cells depleted for Capping Protein. Taken together, these findings indicate a novel interplay between Hippo pathway activity and actin filament dynamics that is essential for normal growth control.
Cdc42-interacting protein 4 is a Src substrate that regulates invadopodia and invasiveness of breast tumors by promoting MT1-MMP endocytosis
Authors: Hu Jinghui , Mukhopadhyay Alka , Truesdell Peter , Chander Harish , Mukhopadhyay Utpal K. , Mak Alan S. , Craig Andrew W. B.
Published: April 2011

Invadopodia are actin-rich membrane protrusions that promote extracellular matrix degradation and invasiveness of tumor cells. Src protein-tyrosine kinase is a potent inducer of invadopodia and tumor metastases. Cdc42-interacting protein 4 (CIP4) adaptor protein interacts with actin regulatory proteins and regulates endocytosis. Here, we show that CIP4 is a Src substrate that localizes to invadopodia in MDA-MB-231 breast tumor cells expressing activated Src (MDA-SrcYF). To probe the function of CIP4 in invadopodia, we established stable CIP4 knockdown in MDA-SrcYF cell lines by RNA interference. Compared with control cells, CIP4 knockdown cells degrade more extracellular matrix (ECM), have increased numbers of mature invadopodia and are more invasive through matrigel. Similar results are observed with knockdown of CIP4 in EGF-treated MDA-MB-231 cells. This inhibitory role of CIP4 is explained by our finding that CIP4 limits surface expression of transmembrane type I matrix metalloprotease (MT1-MMP), by promoting MT1-MMP internalization. Ectopic expression of CIP4 reduces ECM digestion by MDA-SrcYF cells, and this activity is enhanced by mutation of the major Src phosphorylation site in CIP4 (Y471). Overall, our results identify CIP4 as a suppressor of Src-induced invadopodia and invasion in breast tumor cells by promoting endocytosis of MT1-MMP.