bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein kinase A antagonist inhibits β-catenin nuclear translocation, c-Myc and COX-2 expression and tumor promotion in ApcMin/+ mice
Authors: Brudvik Kristoffer W , Paulsen Jan E , Aandahl Einar M , Roald Borghild , Taskén Kjetil 
Published: December 2011

Abstract

Background
The adenomatous polyposis coli (APC) protein is part of the destruction complex controlling proteosomal degradation of β-catenin and limiting its nuclear translocation, which is thought to play a gate-keeping role in colorectal cancer. The destruction complex is inhibited by Wnt-Frz and prostaglandin E2 (PGE2) - PI-3 kinase pathways. Recent reports show that PGE2-induced phosphorylation of β-catenin by protein kinase A (PKA) increases nuclear translocation indicating two mechanisms of action of PGE2 on β-catenin homeostasis.

Findings
Treatment of Apc
Min/+ mice that spontaneously develop intestinal adenomas with a PKA antagonist (Rp-8-Br-cAMPS) selectively targeting only the latter pathway reduced tumor load, but not the number of adenomas. Immunohistochemical characterization of intestines from treated and control animals revealed that expression of β-catenin, β-catenin nuclear translocation and expression of the β-catenin target genes c-Myc and COX-2 were significantly down-regulated upon Rp-8-Br-cAMPS treatment. Parallel experiments in a human colon cancer cell line (HCT116) revealed that Rp-8-Br-cAMPS blocked PGE2-induced β-catenin phosphorylation and c-Myc upregulation.

Conclusion
Based on our findings we suggest that PGE2 act through PKA to promote β-catenin nuclear translocation and tumor development in Apc
Min/+ mice in vivo, indicating that the direct regulatory effect of PKA on β-catenin nuclear translocation is operative in intestinal cancer.
Low-energy structures of clusters supported on metal fcc(110) surfaces
Authors: Zhang Peng , Ma Liuxue , Shao Hezhu , Zhang Jinhu , Zhang Wenxian , Ning Xijing , Zhuang Jun 
Published: December 2011

Abstract
The low-energy structures (LESs) of adatom clusters on a series of metal face-centered cubic (fcc) (110) surfaces are systematically studied by the genetic algorithm, and a simplified model based on the atomic interactions is developed to explain the LESs. Two different kinds of LES group mainly caused by the different next nearest-neighbor (NNN) adatom-adatom interaction are distinguished, although the NNN atomic interaction is much weaker than the nearest-neighbor interaction. For a repulsive NNN atomic interaction, only the linear chain is included in the LES group. However, for an attractive one, type of structure in the LES group is various and replace gradually one by one with cluster size increasing. Based on our model, we also predict the shape feature of the large cluster which is found to be related closely to the ratio of NN and NNN bond energies, and discuss the surface reconstruction in the view of atomic interaction. The results are in accordance with the experimental observations.

PACS: 68.43.Hn; 68.43.Fg.
HIV-1 Group P is unable to antagonize human tetherin by Vpu, Env or Nef
Authors: Sauter Daniel , Hué Stéphane , Petit Sarah J , Plantier Jean-Christophe , Towers Greg J , Kirchhoff Frank , Gupta Ravindra K 
Published: December 2011

Abstract

Background
A new subgroup of HIV-1, designated Group P, was recently detected in two unrelated patients of Cameroonian origin. HIV-1 Group P phylogenetically clusters with SIVgor suggesting that it is the result of a cross-species transmission from gorillas. Until today, HIV-1 Group P has only been detected in two patients, and its degree of adaptation to the human host is largely unknown. Previous data have shown that pandemic HIV-1 Group M, but not non-pandemic Group O or rare Group N viruses, efficiently antagonize the human orthologue of the restriction factor tetherin (BST-2, HM1.24, CD317) suggesting that primate lentiviruses may have to gain anti-tetherin activity for efficient spread in the human population. Thus far, three SIV/HIV gene products (vpu, nef and env) are known to have the potential to counteract primate tetherin proteins, often in a species-specific manner. Here, we examined how long Group P may have been circulating in humans and determined its capability to antagonize human tetherin as an indicator of adaptation to humans.

Results
Our data suggest that HIV-1 Group P entered the human population between 1845 and 1989. Vpu, Env and Nef proteins from both Group P viruses failed to counteract human or gorilla tetherin to promote efficient release of HIV-1 virions, although both Group P Nef proteins moderately downmodulated gorilla tetherin from the cell surface. Notably, Vpu, Env and Nef alleles from the two HIV-1 P strains were all able to reduce CD4 cell surface expression.

Conclusions
Our analyses of the two reported HIV-1 Group P viruses suggest that zoonosis occurred in the last 170 years and further support that pandemic HIV-1 Group M strains are better adapted to humans than non-pandemic or rare Group O, N and P viruses. The inability to antagonize human tetherin may potentially explain the limited spread of HIV-1 Group P in the human population.
Exon duplications in the ATP7A gene: Frequency and Transcriptional Behaviour
Authors: Mogensen Mie , Skjørringe Tina , Kodama Hiroko , Silver Kenneth , Horn Nina , Møller Lisbeth B 
Published: December 2011

Abstract

Background
Menkes disease (MD) is an X-linked, fatal neurodegenerative disorder of copper metabolism, caused by mutations in the ATP7A gene. Thirty-three Menkes patients in whom no mutation had been detected with standard diagnostic tools were screened for exon duplications in the ATP7A gene.

Methods
The ATP7A gene was screened for exon duplications using multiplex ligation-dependent probe amplification (MLPA). The expression level of ATP7A was investigated by real-time PCR and detailed analysis of the ATP7A mRNA was performed by RT-PCR followed by sequencing. In order to investigate whether the identified duplicated fragments originated from a single or from two different X-chromosomes, polymorphic markers located in the duplicated fragments were analyzed.

Results
Partial ATP7A gene duplication was identified in 20 unrelated patients including one patient with Occipital Horn Syndrome (OHS). Duplications in the ATP7A gene are estimated from our material to be the disease causing mutation in 4% of the Menkes disease patients. The duplicated regions consist of between 2 and 15 exons. In at least one of the cases, the duplication was due to an intra-chromosomal event. Characterization of the ATP7A mRNA transcripts in 11 patients revealed that the duplications were organized in tandem, in a head to tail direction. The reading frame was disrupted in all 11 cases. Small amounts of wild-type transcript were found in all patients as a result of exon-skipping events occurring in the duplicated regions. In the OHS patient with a duplication of exon 3 and 4, the duplicated out-of-frame transcript coexists with an almost equally represented wild-type transcript, presumably leading to the milder phenotype.

Conclusions
In general, patients with duplication of only 2 exons exhibit a milder phenotype as compared to patients with duplication of more than 2 exons. This study provides insight into exon duplications in the ATP7A gene.
The soluble biomarker calprotectin (a S100 protein) is associated to ultrasonographic synovitis scores and is sensitive to change in patients with rheumatoid arthritis treated with adalimumab
Authors: Hammer Hilde Berner , Fagerhol Magne K , Wien Tale Norbye , Kvien Tore K 
Published: December 2011

Abstract
Introduction
Calprotectin (MRP8/MRP14, S100A8/A9) is associated with disease activity in patients with rheumatoid arthritis (RA). Ultrasonography (US) is a reliable method for evaluation of synovitis (B-mode (BM) and power Doppler (PD)). The present objectives were to explore in RA patients the associations between calprotectin and a comprehensive US examination, as well as the responsiveness of calprotectin compared to other inflammatory markers during anti-TNF treatment.

Methods
A total of 20 RA patients starting treatment with adalimumab were examined longitudinally by US (BM and PD (semi-quantitative scores 0 to 3) of 78 joints, 36 tendons/tendon groups and 2 bursae) and clinically at baseline and after 1, 3, 6 and 12 months. Associations between the US sum scores and the inflammatory markers calprotectin, serum amyloid A (SAA), CRP and ESR were explored by correlation and linear regression analyses, and the response to treatment was assessed by Standardized Response Mean (SRM).

Results
The inflammatory markers, clinical examinations and US sum scores improved during treatment (P < 0.001). Of the inflammatory markers, calprotectin had the highest correlation coefficients with the total BM and PD sum scores (median (range) 0.59 (0.37 to 0.76) for BM and 0.56 (0.38 to 0.72) for PD). Even higher correlations were found between calprotectin and sum US scores of reduced number of joint counts. Calprotectin made a considerable contribution to total US sum scores in the linear regression analyses (P = 0.001 to 0.031) and among the inflammatory markers, calprotectin had the highest SRM (0.84 at one month).

Conclusions
Calprotectin was associated with the sum scores from a comprehensive US assessment and was responsive to change during anti-TNF treatment. Thus, examination of this leukocyte protein could be of additional value in the assessment of RA patients on biologic treatment.
Regenerative potential of human muscle stem cells in chronic inflammation
Authors: Duijnisveld Bouke J , Bigot Anne , Beenakker Karel GM , Portilho Débora M , Raz Vered , van der Heide Huub JL , Visser Cornelis PJ , Chaouch Soraya , Mamchaoui Kamel , Westendorp Rudi GJ , Mouly Vincent , Butler-Browne Gillian S , Nelissen Rob GHH , Maier Andrea B 
Published: December 2011

Abstract

Introduction

Chronic inflammation is a profound systemic modification of the cellular microenvironment which could affect survival, repair and maintenance of muscle stem cells. The aim of this study was to define the role of chronic inflammation on the regenerative potential of satellite cells in human muscle.

Methods

As a model for chronic inflammation, 11 patients suffering from rheumatoid arthritis (RA) were included together with 16 patients with osteoarthritis (OA) as controls. The mean age of both groups was 64 years, with more females in the RA group compared to the OA group. During elective knee replacement surgery, a muscle biopsy was taken from the distal musculus vastus medialis. Cell populations from four RA and eight OA patients were used for extensive phenotyping because these cell populations showed no spontaneous differentiation and myogenic purity greater than 75% after explantation.

Results

After mononuclear cell explantation, myogenic purity, viability, proliferation index, number of colonies, myogenic colonies, growth speed, maximum number of population doublings and fusion index were not different between RA and OA patients. Furthermore, the expression of proteins involved in replicative and stress-induced premature senescence and apoptosis, including p16, p21, p53, hTERT and cleaved caspase-3, was not different between RA and OA patients. Mean telomere length was shorter in the RA group compared to the OA group.

Conclusions

In the present study we found evidence that chronic inflammation in RA does not affect the in vitro regenerative potential of human satellite cells. Identification of mechanisms influencing muscle regeneration by modulation of its microenvironment may, therefore, be more appropriate.
Variants on the promoter region of PTEN affect breast cancer progression and patient survival
Authors: Heikkinen Tuomas , Greco Dario , Pelttari Liisa M , Tommiska Johanna , Vahteristo Pia , Heikkilä Päivi , Blomqvist Carl , Aittomäki Kristiina , Nevanlinna Heli 
Published: December 2011

Abstract
Introduction
The PTEN gene, a regulator of the phosphatidylinositol-3-kinase (PI3K)/Akt oncogenic pathway, is mutated in various cancers and its expression has been associated with tumor progression in a dose-dependent fashion. We investigated the effect of germline variation in the promoter region of the PTEN gene on clinical characteristics and survival in breast cancer.

Methods
We screened the promoter region of the PTEN gene for germline variation in 330 familial breast cancer cases and further determined the genotypes of three detected PTEN promoter polymorphisms -903GA, -975GC, and -1026CA in a total of 2,412 breast cancer patients to evaluate the effects of the variants on tumor characteristics and disease outcome. We compared the gene expression profiles in breast cancers of 10 variant carriers and 10 matched non-carriers and performed further survival analyses based on the differentially expressed genes.

Results
All three promoter variants associated with worse prognosis. The Cox's regression hazard ratio for 10-year breast cancer specific survival in multivariate analysis was 2.01 (95% CI 1.17 to 3.46) P = 0.0119, and for 5-year breast cancer death or distant metastasis free survival 1.79 (95% CI 1.03 to 3.11) P = 0.0381 for the variant carriers, indicating PTEN promoter variants as an independent prognostic factor. The breast tumors from the promoter variant carriers exhibited a similar gene expression signature of 160 differentially expressed genes compared to matched non-carrier tumors. The signature further stratified patients into two groups with different recurrence free survival in independent breast cancer gene expression data sets.

Conclusions
Inherited variation in the PTEN promoter region affects the tumor progression and gene expression profile in breast cancer. Further studies are warranted to establish PTEN promoter variants as clinical markers for prognosis in breast cancer.
Succinate Dehydrogenase (SDH) D Subunit (SDHD) Inactivation in a Growth-Hormone-Producing Pituitary Tumor: A New Association for SDH?
Authors: Xekouki Paraskevi , Pacak Karel , Almeida Madson , Wassif Christopher A. , Rustin Pierre , Nesterova Maria , de la Luz Sierra Maria , Matro Joey , Ball Evan , Azevedo Monalisa , Horvath Anelia , Lyssikatos Charalampos , Quezado Martha , Patronas Nicholas , Ferrando Barbara , Pasini Barbara , Lytras Aristides , Tolis George , Stratakis Constantine A. 
Published: December 2011

Background:Mutations in the subunits B, C, and D of succinate dehydrogenase (SDH) mitochondrial complex II have been associated with the development of paragangliomas (PGL), gastrointestinal stromal tumors, papillary thyroid and renal carcinoma (SDHB), and testicular seminoma (SDHD).Aim:Our aim was to examine the possible causative link between SDHD inactivation and somatotropinoma.Patients and Methods:A 37-yr-old male presented with acromegaly and hypertension. Other family members were found with PGL. Elevated plasma and urinary levels of catecholamines led to the identification of multiple PGL in the proband in the neck, thorax, and abdomen. Adrenalectomy was performed for bilateral pheochromocytomas (PHEO). A GH-secreting macroadenoma was also found and partially removed via transsphenoidal surgery (TTS). Genetic analysis revealed a novel SDHD mutation (c.298_301delACTC), leading to a frame shift and a premature stop codon at position 133 of the protein. Loss of heterozygosity for the SDHD genetic locus was shown in the GH-secreting adenoma. Down-regulation of SDHD protein in the GH-secreting adenoma by immunoblotting and immunohistochemistry was found. A literature search identified other cases of multiple PGL and/or PHEO in association with pituitary tumors.Conclusion:We describe the first kindred with a germline SDHD pathogenic mutation, inherited PGL, and acromegaly due to a GH-producing pituitary adenoma. SDHD loss of heterozygosity, down-regulation of protein in the GH-secreting adenoma, and decreased SDH enzymatic activity supports SDHD's involvement in the pituitary tumor formation in this patient. Older cases of multiple PGL and PHEO and pituitary tumors in the literature support a possible association between SDH defects and pituitary tumorigenesis.
Incidence of Bleeding in Renally Impaired Patients Receiving Incorrectly Dosed Eptifibatide or Bivalirudin While Undergoing Percutaneous Coronary Intervention
Authors: Taylor Lindsey A , Mauro Vincent F 
Published: December 2011

BACKGROUND: Limited data are available regarding adverse bleeding events associated with antithrombotic agents incorrectly dosed based on renal function in patients receiving percutaneous coronary intervention (PCI). OBJECTIVE: To compare the incidence of bleeding during their hospital stay in patients with reduced renal function receiving incorrect doses of bivalirudin or eptifibatide to the incidence of correct doses, based on manufacturer recommendations; secondary objectives were to determine the incidence of correct dosing based on manufacturer recommendations and the incidence of TIMI (Thrombolysis in Myocardial Infarction) major bleeding. METHODS: A chart review over a 32-month period showed that patients with reduced renal function who received either eptifibatide or bivalirudin during PCI were evaluated for correct dosing based on manufacturer recommendations, bleeding incidence according to the TIMI criteria, and extent of bleeding according to the TIMI and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) criteria. RESULTS: One hundred ninety patients met inclusion criteria, 56 who received eptifibatide and 134 who received bivalirudin. Eptifibatide was dosed incorrectly in 64% of the patients. Patients receiving incorrectly dosed compared to correctly dosed eptifibatide experienced significantly more bleeding (64% vs 35%, respectively, p = 0.04), a greater extent of bleeding based on the TIMI and GUSTO criteria (p = 0.03 and p = 0.009, respectively), and had more TIMI major bleeding (19% vs 5%, respectively). Bivalirudin was dosed incorrectly in 28% of the patients. Patients receiving incorrectly dosed compared to correctly dosed bivalirudin experienced a significantly greater extent of bleeding based on the GUSTO criteria (p = 0.01). There was no significant difference between the incidence of bleeding (37% vs 21%, respectively; p = 0.06), extent of bleeding based on the TIMI criteria (p = 0.058), or incidence of TIMI major bleeding (5% vs 3%). CONCLUSIONS: Patients receiving incorrectly dosed eptifibatide and bivalirudin are susceptible to adverse bleeding events. The occurrence of incorrect dosing offers an opportunity for pharmacist-driven institutional improvement.
Thermodynamic modeling of trivalent Am, Cm and Eu-citrate complexation in concentrated NaClO4media
Authors: Thakur Punam , Xiong Yongliang , Borkowski Marian , Choppin Gregory R. 
Published: December 2011

AbstractThe dissociation constants of citric acid (Cit), and the stability constants of Am3+, Cm3+and Eu3+with Cit were determined as a function of ionic strength (NaClO4) using potentiometric titration and an extraction technique, respectively. The results have shown the presence of both 1:1 and 1:2 complexes under the experimental conditions. A thermodynamic model was constructed to predict the apparent stability constants at different ionic strengths by applying the Pitzer ionic interaction parametersβ(0),β(1), and Cφwhich were obtained to fit the experimental data. Thermodynamic stability constants of M(Cit) and M(Cit)23-(where M = Am3+, Cm3+or Eu3+) were calculated to belog β0101 = 9.91 ± 0.10,log β0102 = 14.47 ± 0.14for Am3+,log β0101 = 9.53 ± 0.16,log β0102 = 14.46 ± 0.16for Cm3+andlog β0101 = 9.82 ± 0.14,log β0102 = 13.31 ± 0.12for Eu3+as obtained by extrapolation to zero ionic strength.
Cross section measurements for gallium in the neutron energy range of 13.5 to 14.8MeV
Authors: Luo Junhua , Liu Rong , Jiang Li 
Published: December 2011

AbstractCross sections for (n,2n), (n,p) and (n,n´α) reactions have been measured on gallium isotopes at the neutron energies of 13.5–14.8 MeV using the activation technique. The monoenergetic neutron beam was producedviathe3H(d,n)4He reaction. The neutron fluences were determined using the monitor reaction27Al(n,α)24Na. The activities induced in the reaction products were measured using high-resolution gamma-ray spectrometry. Data are reported for the following reactions:69Ga(n,2n)68Ga,71Ga(n,2n)70Ga,69Ga(n,p)69mZn,71Ga(n,p)71mZn and71Ga(n,n´α)67Cu. Nuclear model calculations using the code HFTT, which employs the Hauser–Feshbach (statistical model) and exciton model (precompound effects) formalisms, were undertaken to describe the formation of the reaction products. Results are discussed and compared with some corresponding values found in the literature, with some established systematics and with the evaluated data given in ENDF/B-VII.0, CENDL-3.1 and JENDL-4.0.
Intrauterine and postnatal growth failure with normal GH/IGF1 axis and insulin-resistant diabetes in a consanguineous kinship
Authors: Guevara-Aguirre Jaime , Guevara-Aguirre Marco , Hwa Vivian , Prócel Patricio , Saavedra Jeannette , Ostrer Harry , Fang Peng , Rosenfeld Ron G , Kerns Sarah , Rosenbloom Arlan L 
Published: December 2011

ObjectiveTo describe the clinical and biochemical features, and perform molecular analysis for candidate abnormalities in a novel familial syndrome of intrauterine growth retardation (IUGR), failure of an adolescent growth spurt with proportional adult short stature, minimal subluxation of the 5th metacarpal–phalangeal joint, and adult-onset insulin-resistant diabetes unrelated to obesity or other manifestations of metabolic syndrome (MS).DesignDetailed clinical history, auxological, biochemical, radiological, and molecular studies, including DNA analysis andin vitrostudy of the GH/IGF1 pathway.Materials and methodsTen affected adults from two generations of five related families were studied in detail, and information obtained about nine other likely affected individuals.ResultsHeightZ-scores ranged from −7.3 to −3.8. Unaffected parents of the older generation and frequency of confirmed and suspected instances of the syndrome in the two generations studied is consistent with autosomal recessive inheritance. Insulin resistance was uniformly present in seven subjects tested who were not taking insulin. Diabetes severity did not correlate with overweight. Subjects did not have other typical manifestations of MS such as substantial hyperlipidemia, osteoporosis, or hypertension. No biochemical abnormality in the GH/IGF1 axis or molecular defect was found.ConclusionsWhile the association of IUGR and adult MS, including diabetes, has been well documented, these subjects did not have typical manifestations of MS. Abnormalities in common components that could result in a combination of IUGR, severe postnatal growth, and insulin resistance have been ruled out. A mutation in an unidentified gene may affect intrauterine and postnatal growth, with insulin resistance directly affected or as a result of this growth phenomenon.