bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the Nonstructural Proteins of the Bocavirus Minute Virus of Canines
Authors: Sukhu Loretta , Fasina Olufemi , Burger Lisa , Rai Ayushi , Qiu Jianming , Pintel David J. 
Published: November 2012

ABSTRACT
We present a detailed characterization of a single-cycle infection of the bocavirus minute virus of canines (MVC) in canine WRD cells. This has allowed identification of an additional smaller NS protein that derives from an mRNA spliced within the NS gene that had not been previously reported. In addition, we have identified a role for the viral NP1 protein during infection. NP1 is required for read-through of the MVC internal polyadenylation site and, thus, access of the capsid gene by MVC mRNAs. Although the mechanism of NP1's action has not yet been fully elucidated, it represents the first parvovirus protein to be implicated directly in viral RNA processing.
hsp70 and a Novel Axis of Type I Interferon-Dependent Antiviral Immunity in the Measles Virus-Infected Brain
Authors: Kim Mi Young , Shu Yaoling , Carsillo Thomas , Zhang Jianying , Yu Lianbo , Peterson Cornelia , Longhi Sonia , Girod Sarah , Niewiesk Stefan , Oglesbee Michael 
Published: November 2012

ABSTRACTThe major inducible 70-kDa heat shock protein (hsp70) is host protective in a mouse model of measles virus (MeV) brain infection. Transgenic constitutive expression of hsp70 in neurons, the primary target of MeV infection, abrogates neurovirulence in neonatal H-2dcongenic C57BL/6 mice. A significant level of protection is retained after depletion of T lymphocytes, implicating innate immune mechanisms. The focus of the present work was to elucidate the basis for hsp70-dependent innate immunity using this model. Transcriptome analysis of brains from transgenic (TG) and nontransgenic (NT) mice 5 days after infection identified type I interferon (IFN) signaling, macrophage activation, and antigen presentation as the main differences linked to survival. The pivotal role of type I IFN in hsp70-mediated protection was demonstrated in mice with a genetically disrupted type I IFN receptor (IFNAR−/−), where IFNAR−/−eliminated the difference in survival between TG and NT mice. Brain macrophages, not neurons, are the predominant source of type I IFN in the virus-infected brain, andin vitrostudies provided a mechanistic basis by which MeV-infected neurons can induce IFN-β in uninfected microglia in an hsp70-dependent manner. MeV infection induced extracellular release of hsp70 from mouse neuronal cells that constitutively express hsp70, and extracellular hsp70 induced IFN-β transcription in mouse microglial cells through Toll-like receptors 2 and 4. Collectively, our results support a novel axis of type I IFN-dependent antiviral immunity in the virus-infected brain that is driven by hsp70.
Wisconsin Card Sorting Test scores and clinical and sociodemographic correlates in Schizophrenia: multiple logistic regression analysis
Authors: Banno Masahiro , Koide Takayoshi , Aleksic Branko , Okada Takashi , Kikuchi Tsutomu , Kohmura Kunihiro , Adachi Yasunori , Kawano Naoko , Iidaka Tetsuya , Ozaki Norio 
Published: November 2012

ObjectivesThis study investigated what clinical and sociodemographic factors affected Wisconsin Card Sorting Test (WCST) factor scores of patients with schizophrenia to evaluate parameters or items of the WCST.DesignCross-sectional study.SettingPatients with schizophrenia from three hospitals participated.ParticipantsParticipants were recruited from July 2009 to August 2011. 131 Japanese patients with schizophrenia (84 men and 47 women, 43.5±13.8 years (mean±SD)) entered and completed the study. Participants were recruited in the study if they (1) met DSM-IV criteria for schizophrenia; (2) were physically healthy and (3) had no mood disorders, substance abuse, neurodevelopmental disorders, epilepsy or mental retardation. We examined their basic clinical and sociodemographic factors (sex, age, education years, age of onset, duration of illness, chlorpromazine equivalent doses and the positive and negative syndrome scale (PANSS) scores).Primary and secondary outcome measuresAll patients carried out the WCST Keio version. Five indicators were calculated, including categories achieved (CA), perseverative errors in Milner (PEM) and Nelson (PEN), total errors (TE) and difficulties of maintaining set (DMS). From the principal component analysis, we identified two factors (1 and 2). We assessed the relationship between these factor scores and clinical and sociodemographic factors, using multiple logistic regression analysis.ResultsFactor 1 was mainly composed of CA, PEM, PEN and TE. Factor 2 was mainly composed of DMS. The factor 1 score was affected by age, education years and the PANSS negative scale score. The factor 2 score was affected by duration of illness.ConclusionsAge, education years, PANSS negative scale score and duration of illness affected WCST factor scores in patients with schizophrenia. Using WCST factor scores may reduce the possibility of type I errors due to multiple comparisons.
Challenges in implementing government-directed VTE guidance for medical patients: a mixed methods study
Authors: Basey Avril Janette , Krska Janet , Kennedy Tom D , Mackridge Adam John 
Published: November 2012

BackgroundImplementing venous thromboembolism (VTE) risk assessment guidance on admission to hospital has proved difficult worldwide. In 2010, VTE risk assessment in English hospitals was linked to financial sanctions. This study investigated possible barriers and facilitators for VTE risk assessment in medical patients and evaluated the impact of local and national initiatives.SettingAcute Medical Unit in one English National Health Service university teaching hospital.MethodsThis was a mixed methods study; National Research Ethics Service approval was granted. Data were collected over four 1-week periods; November 2009 (1), January 2010 (2), April 2010 (3) and April 2011 (4). Case notes for all medical patients admitted during these periods were reviewed. Thirty-six staff were observed admitting 71 of these patients; 24 observed staff participated in a structured interview.Results876 case notes were reviewed. In total, 82.1% of patients had one or more VTE risk factors and 25.3% one or more bleeding risks. VTE risk assessment rose from a baseline of 6.9–19.6%, following local initiatives, and to 98.7% following financially sanctioned government targets. A similar increase in appropriate prescribing of prophylaxis was seen, but inappropriate prescribing also rose. No staff observed in period 1 conducted VTE risk assessment, risk-assessment forms were largely ignored or discarded during period 2; and electronic recording systems available during period 3 were not accessed. Few patients were asked any VTE-related questions in periods 1, 2 or 3.Interviewees’ actual knowledge of VTE risk was not related to perceived knowledge level. Eight of the 24 staff interviewed were aware of national policies or guidance: none had seen them. Principal barriers identified to risk assessment were: involvement of multiple staff in individual admissions; interruptions; lack of policy awareness; time pressure and complexity of tools.ConclusionsNational financial sanctions appear effective in implementing guidance, where other local measures have failed.
Risk of developing tuberculosis after brief exposure in Norwegian children: results of a contact investigation
Authors: Døllner Henrik , Ramm Christina Terez , Harstad Ingunn , Afset Jan Egil , Sagvik Eli 
Published: November 2012

ObjectiveProlonged exposure to adults with pulmonary tuberculosis is a risk factor for infecting children. We have studied to what extent a brief exposure may increase the risk of being infected in children.DesignObservational study of a tuberculosis contact investigation.Setting7 day-care centres and 4 after-school-care centres in Norway.Participants606 1-year-old to 9-year-old children who were exposed briefly to a male Norwegian with smear-positive pulmonary tuberculosis.Main outcome measuresNumber of children with latent and active tuberculosis detected by routine clinical examination, chest x-ray and use of a Mantoux tuberculin skin test (TST) and an interferon-γ release assay (IGRA).ResultsThe children were exposed to a mean of 6.9 h (range 3–18 h). 2–3 months after the exposure, 11 children (1.8%) had a TST ≥6 mm, 6 (1.0%) had TST 4–5 mm, and 587 (97.2%) had a negative TST result. Two children (0.3%) with negative chest x-rays who were exposed 4.75 and 12 h, respectively, had a positive IGRA test result, and were diagnosed with latent tuberculosis. None developed active tuberculosis.ConclusionsChildren from a high-income country attending day-care and after-school-care centres had low risk of being infected after brief exposure less than 18 h to an adult day-care helper with smear-positive pulmonary tuberculosis.
Stratigraphic restriction of stromatolites in a Middle and Upper Ordovician foreland-platform succession (Ottawa Embayment, eastern Ontario)
Authors: Nehza Odette , Dix George R. 
Published: November 2012

Stromatolites are abundant and widely distributed within two narrow stratigraphic intervals in Middle (Darriwilian) and Upper (lower Turinian) Ordovician strata of the Laurentian foreland interior in the Ottawa Embayment, eastern Ontario. These lithostratigraphic markers coincide with rapid, tectonically driven flooding of the foreland interior and may identify an opportunistic microbial response to nutrient loading with shallow (peritidal, subtidal) marine reworking of terrestrial or nutrient-rich coastal systems. The remaining (Chatfieldian–Edenian) foreland-platform succession represents deeper-water deposition in response to elevated subsidence rates along the Laurentian margin. Stromatolites are absent in this higher-energy setting, but microbial calcite is preserved as coccoid-like microencrustations on skeletal debris. Stromatolites of Darriwilian age are dolomitic, occur in the Carillon Formation, and are part of a regional (200+ km) onlap of peritidal sediment during onset of Taconic orogenesis. Stratiform to large (2 m diameter) low-relief domal stromatolites contain rhythmic laminations of inclusion-rich and -poor dolomicrospar grouped by Fe-oxide-stained erosional surfaces. Domal forms also contain thrombolitic microstructure. Patterns of lamination and stable (C, O) isotopes suggest a balance between abiotic and microbial carbonate production, likely influenced by water depth and temperature. Stromatolites of Turinian age are calcitic and form a regional (80+ km) thin (<8 m) subtidal biostromal unit in the lowermost Pamelia Formation. Their occurrence defines an abrupt vertical transition from initial intrabasinal transgressive subtidal phosphatic siliciclastics and carbonates to an interbasinal stratigraphy of peritidal lime mudstone. Arrhythmic laminations of microbial peloid packstone, with possible eukaryote alga moulds, and locally evaporitic spongiostromate microstructure identify salinity and energy as primary depositional controls. The stromatolite–?eukaryotic association is similar to some modern subtidal microstructures and is part of the reef-community diversification in the Ordovician.
MYC Acts via the PTEN Tumor Suppressor to Elicit Autoregulation and Genome-Wide Gene Repression by Activation of the Ezh2 Methyltransferase
Authors: Kaur Mandeep , Cole Michael D. 
Published: November 2012

Abstract
The control of normal cell growth is a balance between stimulatory and inhibitory signals. MYC is a pleiotropic transcription factor that both activates and represses a broad range of target genes and is indispensable for cell growth. Whereas much is known about gene activation by MYC, there is no established mechanism for the majority of MYC-repressed genes. We report that MYC transcriptionally activates the PTEN tumor suppressor in normal cells to inactivate the phosphoinositide 3-kinase (PI3K) pathway, thus suppressing AKT activation. Suppression of AKT enhances the activity of the EZH2 histone methyltransferase, a subunit of the epigenetic repressor Polycomb Repressive Complex 2 (PRC2), while simultaneously stabilizing the protein. MYC-mediated enhancement in EZH2 protein level and activity results in local and genome-wide elevation in the repressive H3K27me3 histone modification, leading to widespread gene repression including feedback autoregulation of the MYC gene itself. Depletion of either PTEN or EZH2 and inhibition of the PI3K/AKT pathway leads to gene derepression. Importantly, expression of a phospho-defective EZH2 mutant is sufficient to recapitulate nearly half of all MYC-mediated gene repression. We present a novel epigenetic model for MYC-mediated gene repression and propose that PTEN and MYC exist in homeostatic balance to control normal growth, which is disrupted in cancer cells. Cancer Res; 73(2); 695–705. ©2012 AACR.
Epigenetic Regulation by Z-DNA Silencer Function Controls Cancer-Associated ADAM-12 Expression in Breast Cancer: Cross-talk between MeCP2 and NF1 Transcription Factor Family
Authors: Ray Bimal K. , Dhar Srijita , Henry Carolyn , Rich Alexander , Ray Alpana 
Published: November 2012

Abstract
A disintegrin and metalloprotease domain-containing protein 12 (ADAM-12) is upregulated in many human cancers and promotes cancer metastasis. Increased urinary level of ADAM-12 in breast and bladder cancers correlates with disease progression. However, the mechanism of its induction in cancer remains less understood. Previously, we reported a Z-DNA–forming negative regulatory element (NRE) in ADAM-12 that functions as a transcriptional suppressor to maintain a low-level expression of ADAM-12 in most normal cells. We now report here that overexpression of ADAM-12 in triple-negative MDA-MB-231 breast cancer cells and breast cancer tumors is likely due to a marked loss of this Z-DNA–mediated transcriptional suppression function. We show that Z-DNA suppressor operates by interaction with methyl-CpG-binding protein, MeCP2, a prominent epigenetic regulator, and two members of the nuclear factor 1 family of transcription factors, NF1C and NF1X. While this tripartite interaction is highly prevalent in normal breast epithelial cells, both in vitro and in vivo, it is significantly lower in breast cancer cells. Western blot analysis has revealed significant differences in the levels of these 3 proteins between normal mammary epithelial and breast cancer cells. Furthermore, we show, by NRE mutation analysis, that interaction of these proteins with the NRE is necessary for effective suppressor function. Our findings unveil a new epigenetic regulatory process in which Z-DNA/MeCP2/NF1 interaction leads to transcriptional suppression, loss of which results in ADAM-12 overexpression in breast cancer cells. Cancer Res; 73(2); 736–44. ©2012 AACR.
Glutathione-Deficient Mice Have Increased Sensitivity to Transplacental Benzo[a]pyrene-Induced Premature Ovarian Failure and Ovarian Tumorigenesis
Authors: Lim Jinhwan , Lawson Gregory W. , Nakamura Brooke N. , Ortiz Laura , Hur Jin A. , Kavanagh Terrance J. , Luderer Ulrike 
Published: November 2012

Abstract
Polycyclic aromatic hydrocarbons (PAH) such as benzo[a]pyrene (BaP) are ubiquitous environmental pollutants found in tobacco smoke, air pollution, and grilled foods. Prenatal exposure to BaP causes premature reproductive senescence in mice, and other PAHs are transplacental ovarian carcinogens. Glutathione (GSH) is critical for detoxification of the reactive metabolites of PAHs. Therefore, we hypothesized that mice that are genetically deficient in GSH synthesis, due to deletion of the modifier subunit of glutamate cysteine ligase (Gclm), the rate-limiting enzyme in GSH synthesis, have increased destruction of oogonia, premature ovarian failure, and ovarian tumorigenesis after transplacental BaP exposure compared with Gclm+/+ females. Gclm+/− female and male mice were mated, and dams were treated with 0, 2, or 10 mg/kg/d BaP in sesame oil by gavage from gestational days 7 to 16. Compared with oil-treated F1 females of the same genotype, Gclm−/− prenatally BaP-treated females had significantly greater decrements in offspring production than Gclm+/+ BaP-treated females. Similarly, we observed significant BaP dose × Gclm genotype interactions on ovarian follicle counts and ovarian tumor multiplicity at 7.5 months of age, with Gclm−/− females having greater decrements in follicle numbers and more ovarian tumors in response to prenatal BaP exposure than Gclm+/+ females. The ovarian tumors were positive for the epithelial marker cytokeratin. Our results show that prenatal exposure of females to BaP causes premature ovarian failure and ovarian tumorigenesis and that embryonic GSH deficiency due to deletion of Gclm increases sensitivity to these transplacental ovarian effects of BaP. Cancer Res; 73(2); 908–17. ©2012 AACR.
Impact of Ischemia and Procurement Conditions on Gene Expression in Renal Cell Carcinoma
Authors: Liu Nick W. , Sanford Thomas , Srinivasan Ramaprasad , Liu Jack L. , Khurana Kiranpreet , Aprelikova Olga , Valero Vladimir , Bechert Charles , Worrell Robert , Pinto Peter A. , Yang Youfeng , Merino Maria , Linehan W. Marston , Bratslavsky Gennady 
Published: November 2012

AbstractPurpose: Previous studies have shown that ischemia alters gene expression in normal and malignant tissues. There are no studies that evaluated effects of ischemia in renal tumors. This study examines the impact of ischemia and tissue procurement conditions on RNA integrity and gene expression in renal cell carcinoma.Experimental Design: Ten renal tumors were resected without renal hilar clamping from 10 patients with renal clear cell carcinoma. Immediately after tumor resection, a piece of tumor was snap frozen. Remaining tumor samples were stored at 4°C, 22°C, and 37°C and frozen at 5, 30, 60, 120, and 240 minutes. Histopathologic evaluation was conducted on all tissue samples, and only those with greater than 80% tumor were selected for further analysis. RNA integrity was confirmed by electropherograms and quantitated using RNA integrity number index. Altered gene expression was assessed by paired, two-sample t test between the zero time point and aliquots from various conditions obtained from the same tumor.Results: One hundred and forty microarrays were conducted. Some RNA degradation was observed 240 minutes after resection at 37°C. The expression of more than 4,000 genes was significantly altered by ischemia times or storage conditions. The greatest gene expression changes were observed with longer ischemia time and warmer tissue procurement conditions.Conclusion: RNA from kidney cancer remains intact for up to 4 hours post surgical resection regardless of storage conditions. Despite excellent RNA preservation, time after resection and procurement conditions significantly influence gene expression profiles. Meticulous attention to preacquisition variables is of paramount importance for accurate tumor profiling. Clin Cancer Res; 19(1); 42–49. ©2012 AACR.
Magnetic Resonance Imaging Analysis of Rotational Alignment in Patients With Patellar Dislocations
Authors: Diederichs Gerd , Köhlitz Torsten , Kornaropoulos Evgenios , Heller Markus O. , Vollnberg Bernd , Scheffler Sven 
Published: November 2012

Background: The role of anatomic risk factors in patellofemoral instability is not yet fully understood, as they have been observed in patients either alone or in combination and in different degrees of severity. Purpose: To prospectively analyze rotational limb alignment in patients with patellofemoral instability and in controls using magnetic resonance imaging (MRI). Study Design: Cross-sectional study; Level of evidence, 3. Methods: Thirty patients (mean age, 22.9 y; range, 12-41 y) with a history of patellar dislocation and 30 age- and sex-matched controls (mean age, 25.2 y; range, 16-37 y) were investigated. The patients underwent MRI of the leg at 1.5 T using a peripheral angiography coil and a T2-weighted half-Fourier acquisition single-shot turbo spin echo (HASTE) sequence for measuring femoral antetorsion, tibial torsion, knee rotation, and mechanical axis deviation (MAD). The mean values of these parameters were compared between patients and controls. In addition, the patients underwent an assessment to determine the influence of rotational limb alignment on lateral trochlear inclination, trochlear facet asymmetry, trochlear depth, Insall-Salvati index, and tibial tuberosity–trochlear groove distance. Results: Patients had 1.56-fold higher mean femoral antetorsion (20.3° ± 10.4° vs 13.0° ± 8.4°; P < .01) and 1.6-fold higher knee rotation (9.4° ± 5.0° vs 5.7° ± 4.3°; P < .01) compared with controls. Moreover, patients had 2.9 times higher MAD (0.81 ± 0.75 mm vs −0.28 ± 0.87 mm; P < .01). Differences in tibial torsion were not significant. Also, there were no significant correlations between parameters of rotational alignment and standard anatomic risk factors. Conclusion: Our results suggest that some patients with nontraumatic patellar instability have greater internal femoral rotation, greater knee rotation, and a tendency for genu valgum compared with healthy controls. Rotational malalignment may be a primary risk factor in patellar dislocation that has so far been underestimated.
LRF-mediated Dll4 repression in erythroblasts is necessary for hematopoietic stem cell maintenance
Authors: Lee Sung-Uk , Maeda Manami , Ishikawa Yuichi , Li Sierra Min , Wilson Anne , Jubb Adrian M. , Sakurai Nagisa , Weng Lihong , Fiorini Emma , Radtke Freddy , Yan Minhong , MacDonald H. Robson , Chen Ching-Cheng , Maeda Takahiro 
Published: November 2012

Key PointsNotch1/DII4-mediated signals are normally suppressed by LRF, preventing HSCs from premature T-cell differentiation in the bone marrow. Erythroblastic islands may have the capacity to regulate the fate and function of HSCs.
Adaptive evolution of the chrysanthemyl diphosphate synthase gene involved in irregular monoterpene metabolism
Authors: Liu Ping-Li , Wan Jun-Nan , Guo Yan-Ping , Ge Song , Rao Guang-Yuan 
Published: November 2012

Abstract

Background
Chrysanthemyl diphosphate synthase (CDS) is a key enzyme in biosynthetic pathways producing pyrethrins and irregular monoterpenes. These compounds are confined to plants of the tribe Anthemideae of the Asteraceae, and play an important role in defending the plants against herbivorous insects. It has been proposed that the CDS genes arose from duplication of the farnesyl diphosphate synthase (FDS) gene and have different function from FDSs. However, the duplication time toward the origin of CDS and the evolutionary force behind the functional divergence of the CDS gene are still unknown.

Results
Two duplication events were detected in the evolutionary history of the FDS gene family in the Asteraceae, and the second duplication led to the origin of CDS. CDS occurred after the divergence of the tribe Mutisieae from other tribes of Asteraceae but before the birth of the Anthemideae tribe. After its origin, CDS accumulated four mutations in sites homologous to the substrate-binding and catalysis sites of FDS. Of these, two sites were involved in the binding of the nucleophilic substrate isopentenyl diphosphate in FDS. Maximum likelihood analyses showed that some sites in CDS were under positive selection and were scattered throughout primary sequences, whereas in the three-dimensional structure model they clustered in the large central cavity.

Conclusion
Positive selection associated with gene duplication played a major role in the evolution of CDS.