bluuebunny/crossref_metadata_2025_split huggingface dataset:
PRMT1 interacts with AML1-ETO to promote its transcriptional activation and progenitor cell proliferative potential
Authors: Shia Wei-Jong , Okumura Akiko J. , Yan Ming , Sarkeshik Ali , Lo Miao-Chia , Matsuura Shinobu , Komeno Yukiko , Zhao Xinyang , Nimer Stephen D. , Yates John R. , Zhang Dong-Er 
Published: April 2012

Abstract
Fusion protein AML1-ETO, resulting from t(8;21) translocation, is highly related to leukemia development. It has been reported that full-length AML1-ETO blocks AML1 function and requires additional mutagenic events to promote leukemia. We have previously shown that the expression of AE9a, a splice isoform of AML1-ETO, can rapidly cause leukemia in mice. To understand how AML1-ETO is involved in leukemia development, we took advantage of our AE9a leukemia model and sought to identify its interacting proteins from primary leukemic cells. Here, we report the discovery of a novel AE9a binding partner PRMT1 (protein arginine methyltransferase 1). PRMT1 not only interacts with but also weakly methylates arginine 142 of AE9a. Knockdown of PRMT1 affects expression of a specific group of AE9a-activated genes. We also show that AE9a recruits PRMT1 to promoters of AE9a-activated genes, resulting in enrichment of H4 arginine 3 methylation, H3 Lys9/14 acetylation, and transcription activation. More importantly, knockdown of PRMT1 suppresses the self-renewal capability of AE9a, suggesting a potential role of PRMT1 in regulating leukemia development.
Effects of induction and maintenance plus long-term bisphosphonates on bone disease in patients with multiple myeloma: the Medical Research Council Myeloma IX Trial
Authors: Morgan Gareth J. , Davies Faith E. , Gregory Walter M. , Szubert Alex J. , Bell Sue E. , Drayson Mark T. , Owen Roger G. , Ashcroft A. John , Jackson Graham H. , Child J. Anthony 
Published: April 2012

AbstractThe Medical Research Council Myeloma IX Trial (ISRCTNG8454111) examined traditional and thalidomide-based induction and maintenance regimens and IV zoledronic acid (ZOL) and oral clodronate (CLO) in 1960 patients with newly diagnosed multiple myeloma. Overall survival (OS) and skeletal-related event (SRE) data have been reported for the overall trial population. The present analysis investigated optimal therapy regimens for different patient populations in Myeloma IX. Patients were assigned to intensive or nonintensive treatment pathways and randomized to induction cyclophosphamide, vincristine, doxorubicin, and dexamethasone (CVAD) versus cyclophosphamide, thalidomide, and dexamethasone (CTD; intensive) or melphalan and prednisolone versus attenuated oral CTD (CTDa; nonintensive). Patients were also randomized to ZOL or CLO. In the nonintensive pathway, CTDa produced better responses and lower SRE rates than melphalan and prednisolone. ZOL improved OS compared with CLO independently of sex, stage, or myeloma subtype, most profoundly in patients with baseline bone disease or other SREs. In patients treated for ≥ 2 years, ZOL improved OS compared with CLO from randomization (median not reached for either; P = .02) and also from first on-study disease progression (median, 34 months for ZOL vs 27 months for CLO; P = .03). Thalidomide-containing regimens had better efficacy than traditional regimens, and ZOL demonstrated greater benefits than CLO.
Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma
Authors: Cavo Michele , Pantani Lucia , Petrucci Maria Teresa , Patriarca Francesca , Zamagni Elena , Donnarumma Daniela , Crippa Claudia , Boccadoro Mario , Perrone Giulia , Falcone Antonietta , Nozzoli Chiara , Zambello Renato , Masini Luciano , Furlan Anna , Brioli Annamaria , Derudas Daniele , Ballanti Stelvio , Dessanti Maria Laura , De Stefano Valerio , Carella Angelo Michele , Marcatti Magda , Nozza Andrea , Ferrara Felicetto , Callea Vincenzo , Califano Catello , Pezzi Annalisa , Baraldi Anna , Grasso Mariella , Musto Pellegrino , Palumbo Antonio 
Published: April 2012

Abstract
In a randomized, phase 3 study, superior complete/near-complete response (CR/nCR) rates and extended progression-free survival were demonstrated with bortezomib-thalidomide-dexamethasone (VTD) versus thalidomide-dexamethasone (TD) as induction therapy before, and consolidation after, double autologous stem cell transplantation for newly diagnosed myeloma patients (intention-to-treat analysis; VTD, n = 236; TD, n = 238). This per-protocol analysis (VTD, n = 160; TD, n = 161) specifically assessed the efficacy and safety of consolidation with VTD or TD. Before starting consolidation, CR/nCR rates were not significantly different in the VTD (63.1%) and TD arms (54.7%). After consolidation, CR (60.6% vs 46.6%) and CR/nCR (73.1% vs 60.9%) rates were significantly higher for VTD-treated versus TD-treated patients. VTD consolidation significantly increased CR and CR/nCR rates, but TD did not (McNemar test). With a median follow-up of 30.4 months from start of consolidation, 3-year progression-free survival was significantly longer for the VTD group (60% vs 48% for TD). Grade 2 or 3 peripheral neuropathy (8.1% vs 2.4%) was more frequent with VTD (grade 3, 0.6%) versus TD consolidation. The superior efficacy of VTD versus TD as induction was retained despite readministration as consolidation therapy after double autologous transplantation. VTD consolidation therapy significantly contributed to improved clinical outcomes observed for patients randomly assigned to the VTD arm of the study. The study is registered at www.clinicaltrials.gov as #NCT01134484.
Facile synthesis of superhydrophobic surface of ZnO nanoflakes: chemical coating and UV-induced wettability conversion
Authors: Yao Lujun , Zheng Maojun , Li Changli , Ma Li , Shen Wenzhong 
Published: April 2012

AbstractThis work reports an oriented growth process of two-dimensional (2D) ZnO nanoflakes on aluminum substrate through a low temperature hydrothermal technique and proposes the preliminary growth mechanism. A bionic superhydrophobic surface with excellent corrosion protection over a wide pH range in both acidic and alkaline solutions was constructed by a chemical coating treatment with stearic acid (SA) molecules on ZnO nanoflakes. It is found that the superhydrophobic surface of ZnO nanoflake arrays shows a maximum water contact angle (CA) of 157° and a low sliding angle of 8°, and it can be reversibly switched to its initial superhydrophilic state under ultraviolet (UV) irradiation, which is due to the UV-induced decomposition of the coated SA molecules. This study is significant for simple and inexpensive building of large-scale 2D ZnO nanoflake arrays with special wettability which can extend the applications of ZnO films to many other important fields.
Apolipoprotein epsilon 3 alleles are associated with indicators of neuronal resilience
Authors: Aboud Orwa , Mrak Robert E , Boop Frederick , Griffin Sue T 
Published: April 2012

Abstract

Background
Epilepsy is associated with precocious development of Alzheimer-type neuropathological changes, including appearance of senile plaques, neuronal loss and glial activation. As inheritance of APOE ε4 allele(s) is reported to favor this outcome, we sought to investigate neuronal and glial responses that differ according to APOE genotype. With an eye toward defining ways in which APOE ε3 alleles may foster neuronal well-being in epilepsy and/or APOE ε4 alleles exacerbate neuronal decline, neuronal and glial characteristics were studied in temporal lobectomy specimens from epilepsy patients of either APOE ε4,4 or APOE ε3,3 genotype.

Methods
Tissue and/or cellular expressions of interleukin-1 alpha (IL-1α), apolipoprotein E (ApoE), amyloid β (Aβ) precursor protein (βAPP), synaptophysin, phosphorylated tau, and Aβ were determined in frozen and paraffin-embedded tissues from 52 APOE ε3,3 and 7 APOE ε4,4 (0.25 to 71 years) epilepsy patients, and 5 neurologically normal patients using Western blot, RT-PCR, and fluorescence immunohistochemistry.

Results
Tissue levels of IL-1α were elevated in patients of both APOE ε3,3 and APOE ε4,4 genotypes, and this elevation was apparent as an increase in the number of activated microglia per neuron (APOE ε3,3 vs APOE ε4,4 = 3.7 ± 1.2 vs 1.5 ± 0.4; P < 0.05). This, together with increases in βAPP and ApoE, was associated with apparent neuronal sparing in that APOE ε4,4 genotype was associated with smaller neuron size (APOE ε4,4 vs APOE ε3,3 = 173 ± 27 vs 356 ± 45; P ≤ 0.01) and greater DNA damage (APOE ε4,4 vs APOE ε3,3 = 67 ± 10 vs 39 ± 2; P = 0.01). 3) Aβ plaques were noted at early ages in our epilepsy patients, regardless of APOE genotype (APOE ε4,4 age 10; APOE ε3,3 age 17).

Conclusions
Our findings of neuronal and glial events, which correlate with lesser neuronal DNA damage and larger, more robust neurons in epilepsy patients of APOE ε3,3 genotype compared to APOE ε4,4 genotype carriers, are consistent with the idea that the APOE ε3,3 genotype better protects neurons subjected to the hyperexcitability of epilepsy and thus confers less risk of AD (Alzheimer's disease).
Please see related article: http://www.biomedcentral.com/1741-7015/10/36
Polycystic liver disease presenting with an exudative pleural effusion: a case report
Authors: Woolnough Kerry , Palejwala Altav , Bramall Simon 
Published: April 2012

Abstract

Introduction
Polycystic liver disease is asymptomatic in 95% of patients. In the remaining 5% it causes symptoms due to the local mass effect of the polycystic liver. We describe the case of a patient who presented with symptoms of a pleural effusion and was also found to have polycystic liver disease. The effusion recurred despite repeated efforts at drainage and only resolved following surgical debridement of the cystic liver.

Case presentation
A 50-year-old Caucasian woman presented with a two-week history of increasing dyspnoea. An examination revealed a large right pleural effusion and gross hepatomegaly. An ultrasound confirmed a large polycystic liver and diagnostic thoracocentesis revealed an exudate, which was sterile to culture. The pleural effusion proved refractory to drainage and our patient underwent surgery to deroof the main hepatic cysts in an attempt to reduce the pressure on her right diaphragm. The histology was compatible with that of polycystic liver disease. No evidence of malignancy was found. After surgery, our patient had no recurrence of her effusion and, to date, has remained asymptomatic from her polycystic liver disease.

Conclusion
The case in this report illustrates that an exudative pleural effusion is a rare complication of polycystic liver disease. We feel that the mechanical effects of a large polycystic liver, and subsequent disruption of sub-diaphragmatic capillaries, resulted in a persistent exudative pleural effusion. Thus, surgical debulking of the hepatic cysts is required to manage these effusions.
Loss of PPARγ expression by fibroblasts enhances dermal wound closure
Authors: Sha Wei , Thompson Katherine , South Jennifer , Baron Murray , Leask Andrew 
Published: April 2012

Abstract

Background
Peroxisome proliferator-activated receptor (PPAR)γ may be a key regulator of connective tissue deposition and remodeling in vivo. PPARγ expression is reduced in dermal fibroblasts isolated from fibrotic areas of scleroderma patients; PPARγ agonists suppress the persistent fibrotic phenotype of this cell type. Previously, we showed that loss of PPARγ expression in fibroblasts resulted in enhanced bleomycin-induced skin fibrosis. However, whether loss of PPARγ expression in skin fibroblasts affects cutaneous tissue repair or homeostasis is unknown.

Results
Mice deleted for PPARγ in skin fibroblasts show an enhanced rate of dermal wound closure, concomitant with elevated phosphorylation of Smad3, Akt and ERK, and increased expression of proliferating cell nuclear antigen (PCNA), collagen, α-smooth muscle actin (α-SMA) and CCN2. Conversely, dermal homeostasis was not appreciably affected by loss of PPARγ expression.

Conclusion
PPARγ expression by fibroblasts suppresses cutaneous tissue repair. In the future, direct PPARγ antagonists and agonists might be of clinical benefit in controlling chronic wounds or scarring, respectively.
Knockdown of the nucleosome binding protein 1 inhibits the growth and invasion of clear cell renal cell carcinoma cells in vitro and in vivo
Authors: Ji Shi-Qi , Yao Lin , Zhang Xiao-Yu , Li Xue-Song , Zhou Li-Qun 
Published: April 2012

Abstract

Background
The nucleosome binding protein 1 (HMGN5/NSBP1) is a member of the HMGN protein family and is highly expressed in several kinds of cancer. Nevertheless, the role of NSBP1 in clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to confirm the oncogenic role of NSBP1 in ccRCC using in vitro and in vivo models and explore the mechanism by which NSBP1 contributes to ccRCC tumorigenesis.

Methods
NSBP1 expression was detected in renal tissues from 152 ccRCC patients by immunohistochemistry, and examined in ccRCC cell lines by RT-PCR and Western blot analysis. ccRCC cells were transfected by NSBP1 RNAi and cell viability, apoptosis and invasion were detected by cell vitality test, flow cytometry and transwell assay in vitro. Xenograft in nude mice was also employed to examine the tumorigenesis of ccRCC cells depleted of NSBP1.

Results
Immunohistostaining showed strong immunoreactivity of NSBP1 in all ccRCC tissues and NSBP1 expression level was associated with tumor grade (p = 0.04). NSBP1 expression at mRNA and protein levels was high in ccRCC cell lines. Knockdown of NSBP1 induced cell cycle arrest and apoptosis, and inhibited invasion in 786-O cells. Western blot analysis demonstrated increased expression of Bax and decreased expression of Bcl-2, CyclinB1, VEGF, VEGFR-2, MMP-2, MMP-9, c-fos and c-jun in 786-O cells depleted of NSBP1. In vivo study further showed that knockdown of NSBP1 affected the tumorigenesis of ccRCC cells in nude mice.

Conclusions
NSBP1 plays oncogenic role in ccRCCs by promoting cell proliferation and invasion, and could be exploited as a target for ccRCC treatment.
Towards a more accurate annotation of tyrosine-based site-specific recombinases in bacterial genomes
Authors: Van Houdt Rob , Leplae Raphael , Lima-Mendez Gipsi , Mergeay Max , Toussaint Ariane 
Published: April 2012

Abstract

Background
Tyrosine-based site-specific recombinases (TBSSRs) are DNA breaking-rejoining enzymes. In bacterial genomes, they play a major role in the comings and goings of mobile genetic elements (MGEs), such as temperate phage genomes, integrated conjugative elements (ICEs) or integron cassettes. TBSSRs are also involved in the segregation of plasmids and chromosomes, the resolution of plasmid dimers and of co-integrates resulting from the replicative transposition of transposons. With the aim of improving the annotation of TBSSR genes in genomic sequences and databases, which so far is far from robust, we built a set of over 1,300 TBSSR protein sequences tagged with their genome of origin. We organized them in families to investigate: i) whether TBSSRs tend to be more conserved within than between classes of MGE types and ii) whether the (sub)families may help in understanding more about the function of TBSSRs associated in tandem or trios on plasmids and chromosomes.

Results
A total of 67% of the TBSSRs in our set are MGE type specific. We define a new class of actinobacterial transposons, related to Tn554, containing one abnormally long TBSSR and one of typical size, and we further characterize numerous TBSSRs trios present in plasmids and chromosomes of α- and β-proteobacteria.

Conclusions
The simple in silico procedure described here, which uses a set of reference TBSSRs from defined MGE types, could contribute to greatly improve the annotation of tyrosine-based site-specific recombinases in plasmid, (pro)phage and other integrated MGE genomes. It also reveals TBSSRs families whose distribution among bacterial taxa suggests they mediate lateral gene transfer.
Effects of cyclin D1 gene amplification and protein expression on time to recurrence in postmenopausal breast cancer patients treated with anastrozole or tamoxifen: a TransATAC study
Authors: Lundgren Katja , Brown Matthew , Pineda Silvia , Cuzick Jack , Salter Janine , Zabaglo Lila , Howell Anthony , Dowsett Mitch , Landberg Göran ,   the TransATAC investigators
Published: April 2012

Abstract
Introduction
Gene amplification of CCND1 is observed in a subgroup of breast cancers with poor prognosis, whereas overexpression of the protein cyclin D1 has been linked to both worse and better clinical outcome. CCND1 amplification and protein overexpression have also been associated with resistance to treatment with tamoxifen or even to a potentially detrimental effect of tamoxifen.

Methods
To clarify these challenging and partly contrasting treatment predictive and prognostic links for cyclin D1 we analysed a large cohort of postmenopausal breast cancer patients randomised to receive either adjuvant anastrozole or tamoxifen, as part of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial. The CCND1 amplification status and protein expression of cyclin D1 were assessed by chromogenic in situ hybridisation and immunohistochemistry, respectively, in 1,155 postmenopausal, oestrogen-receptor-positive breast cancer patients included in the TransATAC substudy.

Results
Amplification of CCND1 was observed in 8.7% of the tumours and was associated with increased risk of disease recurrence (hazard ratio = 1.61; 95% confidence interval, 1.08 to 2.41) after adjustment for other clinicopathological parameters. In contrast, nuclear expression of cyclin D1 protein was associated with decreased recurrence rate (hazard ratio = 0.6; 95% confidence interval, 0.39 to 0.92). The intensity of nuclear or cytoplasmic expression was not of prognostic value. There was no significant interaction between cyclin D1 status and treatment efficacy, ruling out any major detrimental effect of tamoxifen in CCND1-amplified postmenopausal breast cancer.

Conclusions
In summary, CCND1 amplification and low nuclear expression of cyclin D1 predicted poor clinical outcome in postmenopausal breast cancer patients treated with either anastrozole or tamoxifen.

Trial Registration
Current Controlled Trials ISRCTN18233230.
GEOPHYSICS BRIGHT SPOTS
Authors: Sun Yonghe 
Published: April 2012

Bright Spots is a recurring column written by Yonghe Sun that spotlights articles in our sister publication, Geophysics. The articles featured this month are from the March–April issue of GEOPHYSICS: • A new approach for detecting topographic and geologic information in seismic data by Adam Gersztenkorn • Multicomponent f-x seismic random noise attenuation via vector autoregressive operators by Mostafa Naghizadeh and Mauricio Sacchi. • Hierarchical Bayesian lithology/fluid prediction: a North Sea case study by Kjartan Rimstad, Per Avseth, and Henning Omre. • A new approach for detecting topographic and geologic information in seismic data by Adam Gersztenkorn. • Seismic imaging of the water column deep layer associated with the Deepwater Horizon oil spill by John Hildebrand, Laurence Armi, and Paul Henkart. • 3D migration for rapid imaging of total magnetic intensity data by Glenn Wilson, Michael Zhdanov, Xiaojun Liu, and Le Wan.
Reducing child conduct problems and promoting social skills in a
middle-income country: cluster randomised controlled trial
Authors: Baker-Henningham Helen , Scott Stephen , Jones Kelvyn , Walker Susan 
Published: April 2012

BackgroundThere is an urgent need for effective, affordable interventions to
prevent child mental health problems in low- and middle-income
countries.AimsTo determine the effects of a universal pre-school-based intervention on
child conduct problems and social skills at school and at home.MethodIn a cluster randomised design, 24 community pre-schools in inner-city
areas of Kingston, Jamaica, were randomly assigned to receive the
Incredible Years Teacher Training intervention (n = 12)
or to a control group (n = 12). Three children from each
class with the highest levels of teacher-reported conduct problems were
selected for evaluation, giving 225 children aged 3–6 years. The primary
outcome was observed child behaviour at school. Secondary outcomes were
child behaviour by parent and teacher report, child attendance and
parents' attitude to school. The study is registered as
ISRCTN35476268.ResultsChildren in intervention schools showed significantly reduced conduct
problems (effect size (ES) = 0.42) and increased friendship skills (ES =
0.74) through observation, significant reductions to teacher-reported (ES
= 0.47) and parent-reported (ES = 0.22) behaviour difficulties and
increases in teacher-reported social skills (ES = 0.59) and child
attendance (ES = 0.30). Benefits to parents' attitude to school were not
significant.ConclusionsA low-cost, school-based intervention in a middle-income country
substantially reduces child conduct problems and increases child social
skills at home and at school.
Clinicopathological significance of psychotic experiences in non-psychotic young people: evidence from four population-based studies
Authors: Kelleher I. , Keeley H. , Corcoran P. , Lynch F. , Fitzpatrick C. , Devlin N. , Molloy C. , Roddy S. , Clarke M. C. , Harley M. , Arseneault L. , Wasserman C. , Carli V. , Sarchiapone M. , Hoven C. , Wasserman D. , Cannon M. 
Published: April 2012

BackgroundEpidemiological research has shown that hallucinations and delusions, the classic symptoms of psychosis, are far more prevalent in the population than actual psychotic disorder. These symptoms are especially prevalent in childhood and adolescence. Longitudinal research has demonstrated that psychotic symptoms in adolescence increase the risk of psychotic disorder in adulthood. There has been a lack of research, however, on the immediate clinicopathological significance of psychotic symptoms in adolescence.AimsTo investigate the relationship between psychotic symptoms and non-psychotic psychopathology in community samples of adolescents in terms of prevalence, co-occurring disorders, comorbid (multiple) psychopathology and variation across early v. middle adolescence.MethodData from four population studies were used: two early adolescence studies (ages 11–13 years) and two mid-adolescence studies (ages 13–16 years). Studies 1 and 2 involved school-based surveys of 2243 children aged 11–16 years for psychotic symptoms and for emotional and behavioural symptoms of psychopathology. Studies 3 and 4 involved in-depth diagnostic interview assessments of psychotic symptoms and lifetime psychiatric disorders in community samples of 423 children aged 11–15 years.ResultsYounger adolescents had a higher prevalence (21–23%) of psychotic symptoms than older adolescents (7%). In both age groups the majority of adolescents who reported psychotic symptoms had at least one diagnosable non-psychotic psychiatric disorder, although associations with psychopathology increased with age: nearly 80% of the mid-adolescence sample who reported psychotic symptoms had at least one diagnosis, compared with 57% of the early adolescence sample. Adolescents who reported psychotic symptoms were at particularly high risk of having multiple co-occurring diagnoses.ConclusionsPsychotic symptoms are important risk markers for a wide range of non-psychotic psychopathological disorders, in particular for severe psychopathology characterised by multiple co-occurring diagnoses. These symptoms should be carefully assessed in all patients.