bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression of G-protein–Coupled Receptor Kinase 3 Expression Is a Feature of Classical GBM That Is Required for Maximal Growth
Authors: Woerner B. Mark , Luo Jingqin , Brown Kristin R. , Jackson Erin , Dahiya Sonika M. , Mischel Paul , Benovic Jeffrey L. , Piwnica-Worms David , Rubin Joshua B. 
Published: November 2011

Abstract
G-protein–coupled receptor kinases (GRK) regulate the function of G-protein–coupled receptors (GPCR). Previously, we found that GPCR (CXCR4)-mediated astrocytoma growth was dependent upon abnormally sustained CXCR4 signaling and was correlated with decreased GRK-mediated receptor phosphorylation. As CXCR4 has also been implicated in the stimulation of high-grade glioma growth, we sought to determine whether dysregulation of GRK expression and/or function might also be present in high-grade gliomas. In an analysis of data from The Cancer Genome Atlas, we found that GRK3 expression is frequently decreased in glioblastoma (GBM) of the classical subtype, which possesses signature amplification or mutational activation of the epidermal growth factor (EGF) receptor. We tested the correlation between GRK3 expression and GBM subtypes, as well as the relationship between the activation of the EGF and other growth factor receptor pathways and GRK expression. In analyses of primary GBM tissue and RNA specimens, we found that GRK3 expression is correlated with established criteria for GBM subtyping including expression of EGF receptor, platelet-derived growth factor receptor (PDGFR)α, NF1, PTEN, CDKN2A, and neurofilament. We also found that established drivers of gliomagenesis, the EGF, PDGF, and TGF-β pathways, all regulate GRK expression. Coculture experiments, designed to mimic critical interactions between tumor and brain microvascular endothelial cells, showed that specifically increasing GRK3 expression reduced the trophic effect of endothelial cells on tumor cells. Together, these experiments show that GRK3 is a negative regulator of cell growth whose expression is preferentially reduced in GBM of the classical subtype as a consequence of activity in primary gliomagenic pathways. Mol Cancer Res; 10(1); 156–66. ©2011 AACR.
Metformin Inhibits Cell Proliferation, Migration and Invasion by Attenuating CSC Function Mediated by Deregulating miRNAs in Pancreatic Cancer Cells
Authors: Bao Bin , Wang Zhiwei , Ali Shadan , Ahmad Aamir , Azmi Asfar S. , Sarkar Sanila H. , Banerjee Sanjeev , Kong Dejuan , Li Yiwei , Thakur Shivam , Sarkar Fazlul H. 
Published: November 2011

Abstract
Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States, which is, in part, due to intrinsic (de novo) and extrinsic (acquired) resistance to conventional therapeutics, suggesting that innovative treatment strategies are required for overcoming therapeutic resistance to improve overall survival of patients. Oral administration of metformin in patients with diabetes mellitus has been reported to be associated with reduced risk of pancreatic cancer and that metformin has been reported to kill cancer stem cells (CSC); however, the exact molecular mechanism(s) has not been fully elucidated. In the current study, we examined the effect of metformin on cell proliferation, cell migration and invasion, and self-renewal capacity of CSCs and further assessed the expression of CSC marker genes and microRNAs (miRNA) in human pancreatic cancer cells. We found that metformin significantly decreased cell survival, clonogenicity, wound-healing capacity, sphere-forming capacity (pancreatospheres), and increased disintegration of pancreatospheres in both gemcitabine-sensitive and gemcitabine-resistant pancreatic cancer cells. Metformin also decreased the expression of CSC markers,CD44, EpCAM,EZH2, Notch-1, Nanog and Oct4, and caused reexpression of miRNAs (let-7a,let-7b, miR-26a, miR-101, miR-200b, and miR-200c) that are typically lost in pancreatic cancer and especially in pancreatospheres. We also found that reexpression of miR-26a by transfection led to decreased expression of EZH2 and EpCAM in pancreatic cancer cells. These results clearly suggest that the biologic effects of metformin are mediated through reexpression of miRNAs and decreased expression of CSC-specific genes, suggesting that metformin could be useful for overcoming therapeutic resistance of pancreatic cancer cells. Cancer Prev Res; 5(3); 355–64. ©2011 AACR.
Taking charge after stroke: promoting self-directed rehabilitation to improve quality of life – a randomized controlled trial
Authors: Harwood Matire , Weatherall Mark , Talemaitoga Api , Barber P Alan , Gommans John , Taylor William , McPherson Kathryn , McNaughton Harry 
Published: November 2011

Objective: Few community interventions following stroke enhance activity, participation or quality of life. We tested two novel community interventions designed to promote self-directed rehabilitation following stroke. Design: This was a randomized, controlled parallel group 2×2 trial. Setting: Community. Participants: Maori and Pacific New Zealanders, >15 years old, randomized within three months of a new stroke. Interventions: A DVD of four inspirational stories by Maori and Pacific people with stroke and a ‘Take Charge Session’ – a single structured risk factor and activities of daily living assessment, designed to facilitate self-directed rehabilitation. Main measures: Primary outcomes were Health-related Quality of Life (Physical Component Summary (PCS) and Mental Component Summary (MCS) scores of the Short Form 36 (SF-36)) 12 months from randomization. Secondary outcomes were Barthel Index, Frenchay Activities Index, Carer Strain Index and modified Rankin score. Results: One hundred and seventy-two people were randomized with 139 (80.8%) followed up at 12 months post randomization. The effect of the Take Charge Session on SF-36 PCS at 12 months was 6.0 (95% confidence interval (CI) 2.0 to 10.0) and of the DVD was 0.9 (95% CI −3.1 to 4.9). Participants allocated to the Take Charge Session were less likely to have a modified Rankin score of >2 (odds ratio (OR) 0.42, 95% CI 0.2 to 0.89) and their carers had lower (better) Carer Strain Index scores (−1.5, 95% CI −2.8 to −0.1). Conclusion: A simple, low-cost intervention in the community phase of stroke recovery aiming to promote self-directed rehabilitation improved outcomes.
Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007
Authors: Dores Graça M. , Devesa Susan S. , Curtis Rochelle E. , Linet Martha S. , Morton Lindsay M. 
Published: November 2011

Abstract
Since 2001, the World Health Organization classification for hematopoietic and lymphoid neoplasms has provided a framework for defining acute leukemia (AL) subtypes, although few population-based studies have assessed incidence patterns and patient survival accordingly. We assessed AL incidence rates (IRs), IR ratios (IRRs), and relative survival in the United States (2001-2007) in one of the first population-based, comprehensive assessments. Most subtypes of acute myeloid leukemia (AML) and acute lymphoblastic leukemia/lymphoma (ALL/L) predominated among males, from twice higher incidence of T-cell ALL/L among males than among females (IRR = 2.20) to nearly equal IRs of acute promyelocytic leukemia (APL; IRR = 1.08). Compared with non-Hispanic whites, Hispanics had significantly higher incidence of B-cell ALL/L (IRR = 1.64) and APL (IRR = 1.28); blacks had lower IRs of nearly all AL subtypes. All ALL/L but only some AML subtypes were associated with a bimodal age pattern. Among AML subtypes, survival was highest for APL and AML with inv(16). B-cell ALL/L had more favorable survival than T-cell ALL/L among the young; the converse occurred at older ages. Limitations of cancer registry data must be acknowledged, but the distinct AL incidence and survival patterns based on the World Health Organization classification support biologic diversity that should facilitate etiologic discovery, prognostication, and treatment advances.
Whole genome resequencing of black Angus and Holstein cattle for SNP and CNV discovery
Authors: Stothard Paul , Choi Jung-Woo , Basu Urmila , Sumner-Thomson Jennifer M , Meng Yan , Liao Xiaoping , Moore Stephen S 
Published: November 2011

Abstract

Background
One of the goals of livestock genomics research is to identify the genetic differences responsible for variation in phenotypic traits, particularly those of economic importance. Characterizing the genetic variation in livestock species is an important step towards linking genes or genomic regions with phenotypes. The completion of the bovine genome sequence and recent advances in DNA sequencing technology allow for in-depth characterization of the genetic variations present in cattle. Here we describe the whole-genome resequencing of two Bos taurus bulls from distinct breeds for the purpose of identifying and annotating novel forms of genetic variation in cattle.

Results
The genomes of a Black Angus bull and a Holstein bull were sequenced to 22-fold and 19-fold coverage, respectively, using the ABI SOLiD system. Comparisons of the sequences with the Btau4.0 reference assembly yielded 7 million single nucleotide polymorphisms (SNPs), 24% of which were identified in both animals. Of the total SNPs found in Holstein, Black Angus, and in both animals, 81%, 81%, and 75% respectively are novel. In-depth annotations of the data identified more than 16 thousand distinct non-synonymous SNPs (85% novel) between the two datasets. Alignments between the SNP-altered proteins and orthologues from numerous species indicate that many of the SNPs alter well-conserved amino acids. Several SNPs predicted to create or remove stop codons were also found. A comparison between the sequencing SNPs and genotyping results from the BovineHD high-density genotyping chip indicates a detection rate of 91% for homozygous SNPs and 81% for heterozygous SNPs. The false positive rate is estimated to be about 2% for both the Black Angus and Holstein SNP sets, based on follow-up genotyping of 422 and 427 SNPs, respectively. Comparisons of read depth between the two bulls along the reference assembly identified 790 putative copy-number variations (CNVs). Ten randomly selected CNVs, five genic and five non-genic, were successfully validated using quantitative real-time PCR. The CNVs are enriched for immune system genes and include genes that may contribute to lactation capacity. The majority of the CNVs (69%) were detected as regions with higher abundance in the Holstein bull.

Conclusions
Substantial genetic differences exist between the Black Angus and Holstein animals sequenced in this work and the Hereford reference sequence, and some of this variation is predicted to affect evolutionarily conserved amino acids or gene copy number. The deeply annotated SNPs and CNVs identified in this resequencing study can serve as useful genetic tools, and as candidates in searches for phenotype-altering DNA differences.
Mucosal atrophy in collagenous colitis: a case report
Authors: Majores Michael , Wunsch Steffen , Blume Bernd , Fischer Hans-Peter , Reichel Christoph 
Published: November 2011

Abstract

Background
Mucosal atrophy as a potential cause of impaired colonic compliance has not yet been described as a complication in Collagenous Colitis (CC).

Case presentation
We present a 51-year-old female patient with a 20-year history of diarrhea and diagnosed with CC ten years prior to her presentation. We reviewed reports from three colonoscopies performed after the diagnosis. Overall 12 biopsies obtained in the last two colonoscopies were re-analyzed by two pathologists blinded to the aim of the study. Besides the typical histological findings of CC, the endoscopic appearance was normal, and no histological signs of atrophy were found during the first colonoscopy. Surprisingly, the second and third colonoscopy revealed a region of advanced segmental mucosal atrophy in the cecum with the mucosal height normalizing toward the transverse colon. This pattern of atrophy was inversely related to the pattern of sub-epithelial collagen deposition, which increased toward the rectum.

Conclusion
If no chance occurrence, our observation supports the idea that additional factors, probably luminal in nature, may be co-responsible for the mucosal atrophy in this case. Thus, mucosal atrophy in the proximal colon appears to be a new candidate among the growing list of rare complications associated with long standing CC.
Ozonated autohemotherapy: protection of kidneys from ischemia in rats subjected to unilateral nephrectomy
Authors: Foglieni Chiara , Fulgenzi Alessandro , Belloni Daniela , Sciorati Clara , Ferrero Elisabetta , Ferrero Maria Elena 
Published: November 2011

Abstract

Background
Ozonated autohemotherapy (OA) has been previously successfully used in the treatment of patients affected by peripheral occlusive arterial disease. OA consists of an intrafemoral reinfusion of autologous blood previously exposed to a mixture of oxygen/ozone (O2/O3). This study analyzes the effects of OA in protecting rat kidney from ischemia and ischemia/reperfusion damage.

Methods
We performed OA 30 min before the induction of 60 min renal ischemia or at the induction of 60 min postischemic reperfusion in rats subjected to unilateral nephrectomy. In addition, to evidence the possible protection induced by O2/O3 on endothelial functions, the present study analyzes the in vitro effects of O2/O3 on oxygen consumption by human umbilical vein endothelial cells (HUVEC).

Results
1) OA preserves rat kidney functions and architecture, as demonstrated by the improved levels of serum creatinine and blood urea nitrogen and by histology; 2) such protection does not correlate with the increase of plasmatic nitric oxide, but is compatible with a focal renal increase of renal βNADPH-diaphorase; 3) treatment of HUVEC with O2/O3 significantly increases both the rate of oxygen consumption and the mitochondrial activity assessed by confocal microscopy.

Conclusion
The preservation of the mitochondrial activity of endothelium could in vivo limit the endothelial dysfunction provoked by the Isc or Isc/R processes.
Microalgae as bioreactors for bioplastic production
Authors: Hempel Franziska , Bozarth Andrew S , Lindenkamp Nicole , Klingl Andreas , Zauner Stefan , Linne Uwe , Steinbüchel Alexander , Maier Uwe G 
Published: November 2011

Abstract

Background
Poly-3-hydroxybutyrate (PHB) is a polyester with thermoplastic properties that is naturally occurring and produced by such bacteria as Ralstonia eutropha H16 and Bacillus megaterium. In contrast to currently utilized plastics and most synthetic polymers, PHB is biodegradable, and its production is not dependent on fossil resources making this bioplastic interesting for various industrial applications.

Results
In this study, we report on introducing the bacterial PHB pathway of R. eutropha H16 into the diatom Phaeodactylum tricornutum, thereby demonstrating for the first time that PHB production is feasible in a microalgal system. Expression of the bacterial enzymes was sufficient to result in PHB levels of up to 10.6% of algal dry weight. The bioplastic accumulated in granule-like structures in the cytosol of the cells, as shown by light and electron microscopy.

Conclusions
Our studies demonstrate the great potential of microalgae like the diatom P. tricornutum to serve as solar-powered expression factories and reveal great advantages compared to plant based production systems.
Enhanced photo-sensitivity through an increased light-trapping on Si by surface nano-structuring using MWCNT etch mask
Authors: Hwang Min-Young , Kim Hyungsuk , Kim Eun-Soo , Lee Jihoon , Koo Sang-Mo 
Published: November 2011

AbstractWe demonstrate an enhanced photo-sensitivity (PS) through an increased light-trapping using surface nano-structuring technique by inductively coupled plasma (ICP) etching on multi-walled carbon nanotube (MWCNT) etch masked Si with hexamethyl-disilazane (HMDS) dispersion. In order for a systematic comparison, four samples are prepared, respectively, by conventional photolithography and ICP etching using MWCNT as a etch mask. MWCNT-etched Si with HMDS dispersion shows the highest RMS roughness and the lowest reflectance of the four. Two test device structures are fabricated with active regions of bare-Si as a reference and MWCNT etch masked Si with HMDS dispersion. The increased light-trapping was most significant at mid-UV, somewhat less at visible and less noticeable at infrared. With an ICP-etched Si using CNT HMDS dispersion, PS is very sharply increased. This result can lead to applications in optoelectronics where the enhancement in light-trapping is important.
Thermal stability of hepatitis E virus assessed by a molecular biological approach
Authors: Schielke Anika , Filter Matthias , Appel Bernd , Johne Reimar 
Published: November 2011

Abstract

Background
Hepatitis E virus (HEV) is a pathogen of emerging concern in industrialized countries. The consumption of wild boar meat has been identified as one risk factor for autochthonous HEV infections. Only limited information is available about thermal stability of HEV, mainly due to the lack of rapid and efficient cell culture systems for measurement of HEV infectivity.

Methods
A molecular biological method was implemented in order to distinguish disassembled from intact viral particles using RNase treatment followed by quantitative real-time RT-PCR. The method was applied to a wild boar liver suspension containing HEV genotype 3.

Results
Time-course analyses indicated that the decline of protected RNA could be described by a biphasic model with an initial decrease followed by a stationary phase. The stationary phase was reached after 1 hour at 4°C, 3 days at 22°C and 7 days at 37°C with log reductions of 0.34, 0.45 and 1.24, respectively. Protected RNA was detectable until the end of the experiments at day 50 or 70. Heat exposure for 1 minute resulted in a log reduction of 0.48 at 70°C and increased with higher temperatures to 3.67 at 95°C. Although HEV infectivity titration by inoculation of the liver suspension onto three cell lines did not succeed, the results of the RNase-based method are in accordance with published cell culture-based data.

Conclusions
Measurement of intact viral particles using the RNase-based method may provide data on the stability of RNA viruses when cell culture-based infectivity titrations are not efficient or not available. The method enables processing of large sample numbers and may be suitable to estimate stability of HEV in different types of food.
Improved Bevirimat resistance prediction by combination of structural and sequence-based classifiers
Authors: Dybowski J Nikolaj , Riemenschneider Mona , Hauke Sascha , Pyka Martin , Verheyen Jens , Hoffmann Daniel , Heider Dominik 
Published: November 2011

Abstract

Background
Maturation inhibitors such as Bevirimat are a new class of antiretroviral drugs that hamper the cleavage of HIV-1 proteins into their functional active forms. They bind to these preproteins and inhibit their cleavage by the HIV-1 protease, resulting in non-functional virus particles. Nevertheless, there exist mutations in this region leading to resistance against Bevirimat. Highly specific and accurate tools to predict resistance to maturation inhibitors can help to identify patients, who might benefit from the usage of these new drugs.

Results
We tested several methods to improve Bevirimat resistance prediction in HIV-1. It turned out that combining structural and sequence-based information in classifier ensembles led to accurate and reliable predictions. Moreover, we were able to identify the most crucial regions for Bevirimat resistance computationally, which are in line with experimental results from other studies.

Conclusions
Our analysis demonstrated the use of machine learning techniques to predict HIV-1 resistance against maturation inhibitors such as Bevirimat. New maturation inhibitors are already under development and might enlarge the arsenal of antiretroviral drugs in the future. Thus, accurate prediction tools are very useful to enable a personalized therapy.
Slice orientation and muscarinic acetylcholine receptor activation determine the involvement of N-methyl D-aspartate receptor subunit GluN2B in hippocampal area CA1 long-term depression
Authors: Bartlett Thomas E , Lu Jie , Wang Yu Tian 
Published: November 2011

Abstract

Background
The contribution of different GluN2 subunits of the N-methyl D-aspartate (NMDA) receptor to the induction of bidirectional hippocampal synaptic plasticity is a controversial topic. As both supporting and refuting evidence for the hypothesis of subunit specialization in opposing directions of plasticity has accumulated since it was first proposed a few years ago, we hypothesize that differences in experimental conditions may have in part contributed to some of the inconsistent results from these studies. Here we investigate the controversial hypothesis that long-term depression (LTD) is preferentially induced by GluN2B-containing NMDA receptors in area CA1 of hippocampal slices.

Results
We find that brain slices from 2-3 week old rats prepared in the sagittal orientation have GluN2B-independent LTD whereas slices prepared in the coronal orientation have GluN2B-dependent LTD. There was no difference between the orientations in the fraction of the NMDAR EPSC sensitive to a GluN2B-selective antagonist, leading us to believe that the intracellular signaling properties of the NMDARs were different in the two preparations. Coronal slices had greater association of LTD-related intracellular signaling protein RasGRF1 with GluN2B relative to sagittal slices. Antagonism of muscarinic acetylcholine receptors (mAChRs) in the sagittal slices returned LTD to a GluN2B-dependent form and increased the association of GluN2B with RasGRF1.

Conclusions
These results suggest a novel form of NMDAR modulation by mAChRs and clarify some disagreement in the literature.
Use of Natriuretic Peptides to Guide and Monitor Heart Failure Therapy
Authors: Richards A Mark , Troughton Richard W 
Published: November 2011

Abstract

BACKGROUND
Plasma B-type cardiac natriuretic peptides reflect cardiac structure and function and have proven roles in assisting in the diagnosis of acute heart failure. They are independent prognostic indicators across the full spectrum of cardiovascular disease. Serial changes in plasma B-type cardiac natriuretic peptides parallel prognosis in chronic heart failure. Beneficial responses to medications and devices used in the treatment of heart failure are associated with decreases in plasma B-type peptide concentrations. This effect has led to the hypothesis that intensified treatment directed at reducing B-peptide concentrations may improve outcomes in heart failure.

CONTENT
The efficacy of serial measurements of plasma B-type peptides in guiding titration of therapy for chronic heart failure has been the subject of several randomized controlled trials reported in the peer-reviewed literature since 2000. These reports are summarized in this review. Trial design, characteristics of the heart-failure population studied, duration of follow-up, exact end points recorded, and target peptide concentrations pursued all differ somewhat between trials. In addition, in studies in which benefits were seen, the exact mechanisms mediating the improvements in outcome were unclear. However, an overall consistency is emerging that is supported by 2 metaanalyses.

SUMMARY
In aggregate the existing trial data suggest that adjustment of treatment in chronic heart failure according to serial B-type peptide measurements, used in conjunction with established clinical methods, is likely to reduce cardiac mortality and hospital admissions with heart failure, at least in patients with systolic heart failure who are younger than 75 years and relatively free of comorbidities.