bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiviral Activity of Salmonid Gamma Interferon against Infectious Pancreatic Necrosis Virus and Salmonid Alphavirus and Its Dependency on Type I Interferon
Authors: Sun Baojian , Skjæveland Ingrid , Svingerud Tina , Zou Jun , Jørgensen Jorunn , Robertsen Børre 
Published: June 2011

ABSTRACT
We investigated the antiviral activity and gene induction properties of interferon gamma (IFN-γ) compared to type I IFN (IFNa1) in Atlantic salmon. IFN-γ protected salmon cells against infectious pancreatic necrosis virus (IPNV)-induced cytopathic effect (CPE), reduced virus titers, and inhibited the synthesis of the viral structural protein VP3. Moreover, IFN-γ showed potent antiviral activity against salmonid alphavirus 3 (SAV3) measured as a reduction in virus nsP1 transcripts. IFN-γ (a type II IFN) had less specific antiviral activity against IPNV than IFNa1, showing a half-maximal effective concentration of 1.6 ng/ml versus 31 pg/ml determined in the CPE reduction assay. Compared to IFNa1, IFN-γ was a more effective inducer of the antiviral protein GBP, several interferon regulatory transcription factors (IRFs), and the chemokine IP-10. The antiviral activity of IFN-γ may also in part be ascribed to upregulation of Mx, ISG15, and viperin. These are typical type I IFN-induced genes in mammals and were also more strongly induced by IFNa1 than by IFN-γ in salmon cells. Fish and mammalian IFN-γ thus show strikingly similar gene induction properties. Interestingly, the antiviral activity of IFN-γ against IPNV and SAV3 and its ability to induce Mx and ISG15 markedly decreased in the presence of neutralizing antiserum against IFNa1. In contrast, antiIFNa1 had no effect on the induction of IRF-1 and IP-10 by IFN-γ. This suggests that the antiviral activity of IFN-γ is partially dependent on IFNa induction. However, because antiIFNa1 could not abolish the IFN-γ-mediated induction of Mx and ISG15 completely, IFN-γ may possibly also induce such genes directly.
Adenovirus Type 5 Early Region 1B 55K Oncoprotein-Dependent Degradation of Cellular Factor Daxx Is Required for Efficient Transformation of Primary Rodent Cells
Authors: Schreiner Sabrina , Wimmer Peter , Groitl Peter , Chen Shuen-Yuan , Blanchette Paola , Branton Philip E. , Dobner Thomas 
Published: June 2011

ABSTRACTEarly region 1B 55K (E1B-55K) from adenovirus type 5 (Ad5) is a multifunctional regulator of lytic infection and contributesin vitroto complete cell transformation of primary rodent cells in combination with Ad5 E1A. Inhibition of p53 activated transcription plays a key role in processes by which E1B-55K executes its oncogenic potential. Nevertheless, additional functions of E1B-55K or further protein interactions with cellular factors of DNA repair, transcription, and apoptosis, including Mre11, PML, and Daxx, may also contribute to the transformation process. In line with previous results, we performed mutational analysis to define a Daxx interaction motif within the E1B-55K polypeptide. The results from these studies showed that E1B-55K/Daxx binding is not required for inhibition of p53-mediated transactivation or binding and degradation of cellular factors (p53/Mre11). Surprisingly, these mutants lost the ability to degrade Daxx and showed reduced transforming potential in primary rodent cells. In addition, we observed that E1B-55K lacking the SUMO-1 conjugation site (SCS/K104R) was sufficient for Daxx interaction but no longer capable of E1B-55K-dependent proteasomal degradation of the cellular factor Daxx. These results, together with the observation that E1B-55K SUMOylation is required for efficient transformation, provides evidence for the idea that SUMO-1-conjugated E1B-55K-mediated degradation of Daxx plays a key role in adenoviral oncogenic transformation. We assume that the viral protein contributes to cell transformation through the modulation of Daxx-dependent pathways. This further substantiates the assumption that further mechanisms for efficient transformation of primary cells can be separated from functions required for the inhibition of p53-stimulated transcription.
The E7 Open Reading Frame Acts in
cis
and in
trans
To Mediate Differentiation-Dependent Activities in the Human Papillomavirus Type 16 Life Cycle
Authors: Bodily Jason M. , Mehta Kavi P. M. , Cruz Linda , Meyers Craig , Laimins Laimonis A. 
Published: June 2011

ABSTRACT

Human papillomaviruses (HPVs) are the causative agents of several important genital and other mucosal cancers. The HPV16 E7 gene encodes a viral oncogene that is necessary for the continued growth of cancer cells, but its role in the normal, differentiation-dependent life cycle of the virus is not fully understood. The function of E7 in the viral life cycle was examined using a series of mutations of E7 created in the context of the complete HPV16 genome. The effect of these E7 mutations on key events of the viral life cycle, including immortalization, episomal maintenance, late promoter activation, and infectious virion synthesis, was examined. Our studies show that the pRb binding domain is indispensable for early viral activities, whereas the C-terminal zinc finger domain contributed primarily to very late events. Mutations of the casein kinase II phosphorylation site caused a complex phenotype involving both the function of E7 protein and a
cis
element necessary for the activation of the late promoter, identifying for the first time a promoter element important for late promoter function in the context of the viral genome. All mutant genomes tested showed reduced viral titers following growth in organotypic raft cultures. These studies clarify the role of E7 as a regulator of late events in the differentiation-dependent HPV life cycle.
Alteration of the Chronic Wasting Disease Species Barrier byIn VitroPrion Amplification
Authors: Kurt Timothy D. , Seelig Davis M. , Schneider Jay R. , Johnson Christopher J. , Telling Glenn C. , Heisey Dennis M. , Hoover Edward A. 
Published: June 2011

ABSTRACTChronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of cervids now detected in 19 states of the United States, three Canadian provinces, and South Korea. Whether noncervid species can be infected by CWD and thereby serve as reservoirs for the infection is not known. To investigate this issue, we previously used serial protein misfolding cyclic amplification (sPMCA) to demonstrate that CWD prions can amplify in brain homogenates from several species sympatric with cervids, including prairie voles (Microtus ochrogaster) and field mice (Peromyscusspp.). Here, we show that prairie voles are susceptible to mule deer CWD prionsin vivoand that sPMCA amplification of CWD prions in vole brain enhances the infectivity of CWD for this species. Prairie voles inoculated with sPMCA products developed clinical signs of TSE disease approximately 300 days prior to, and more consistently than, those inoculated with CWD prions from deer brain. Moreover, the deposition patterns and biochemical properties of protease-resistant form of PrP (PrPRES) in the brains of affected voles differed from those in cervidized transgenic (CerPrP) mice infected with CWD. In addition, voles inoculated orally with sPMCA products developed clinical signs of TSE and were positive for PrPRESdeposition, whereas those inoculated orally with deer-origin CWD prions did not. These results demonstrate that transspecies sPMCA of CWD prions can enhance the infectivity and adapt the host range of CWD prions and thereby may be useful to assess determinants of prion species barriers.
SH2-Containing Inositol 5′-Phosphatase Inhibits Transformation of Abelson Murine Leukemia Virus
Authors: Fessler Shawn P. , Rosenberg Naomi , Baughn Linda B. 
Published: June 2011

ABSTRACT
v-Abl protein tyrosine kinase encoded by Abelson murine leukemia virus (Ab-MLV) transforms pre-B cells. Transformation requires the phosphatidylinositol 3-kinase (PI3K) pathway. This pathway is antagonized by SH2-containing inositol 5′-phosphatase (SHIP), raising the possibility that v-Abl modulates PI3K signaling through SHIP. Consistent with this, we show that v-Abl expression reduces levels of full-length p145 SHIP in a v-Abl kinase activity-dependent fashion. This event requires signals from the Abl SH2 domain but not the carboxyl terminus. Forced expression of full-length SHIP significantly reduces Ab-MLV pre-B-cell transformation. Therefore, reduction of SHIP protein by v-Abl is a critical component in Ab-MLV transformation.
Repeated Application of Low-Frequency Electroacupuncture Improves High-Fructose Diet-Induced Insulin Resistance in Rats
Authors: Tominaga Atsushi , Ishizaki Naoto , Naruse Yoshihisa , Kitakoji Hiroshi , Yamamura Yoshiharu 
Published: June 2011

Background Insulin resistance is frequently present in obesity and during the development of type 2 diabetes mellitus. Objective The purpose of the present study was to investigate the effect of electroacupuncture (EA) on high-fructose diet (HFD)-induced insulin resistance. Methods Male Wistar rats were fed HFD for 4 weeks and developed insulin resistance. Insulin sensitivity was assessed by clamp. The number of animals was seven, eight and seven in the control, HFD and HFD+EA groups, respectively. AMP-activated protein kinase (AMPK) and glucose transporter 4 (GLUT4) in skeletal muscle were measured by Western blotting analysis (n=7 in each group). EA stimulation was carried out 12 times over 4 weeks at an intensity of 1–3 mA and a frequency of 2/15 Hz in a conscious state without restraint. Results There was no significant difference in mean body weight and fasting blood glucose concentration between groups at the end of the experiment. The mean glucose infusion rate during the clamp was significantly lower in the HFD group than in controls (p<0.05). There was no significant difference in expression of GLUT4 in skeletal muscle in the control and each group. Phosphorylated AMPKα (Thr172) in skeletal muscle showed a significant increase immediately after the final EA stimulation when compared with the control group (p<0.05). Conclusion Repeated application of EA is capable of improving diet-induced insulin resistance, probably through activation of AMPK signalling pathways in skeletal muscle. These results suggest that repeated application of EA may have beneficial effects on diet-induced insulin resistance.
Predictors of hospitalised patients' preferences for physician-directed medical decision-making
Authors: Chung Grace S , Lawrence Ryan E , Curlin Farr A , Arora Vineet , Meltzer David O 
Published: June 2011

BackgroundAlthough medical ethicists and educators emphasise patient-centred decision-making, previous studies suggest that patients often prefer their doctors to make the clinical decisions.ObjectiveTo examine the associations between a preference for physician-directed decision-making and patient health status and sociodemographic characteristics.MethodsSociodemographic and clinical information from all consenting general internal medicine patients at the University of Chicago Medical Center were examined. The primary objectives were to (1) assess the extent to which patients prefer an active role in clinical decision-making, and (2) determine whether religious service attendance, the importance of religion, self-rated spirituality, Charlson Comorbidity Index, self-reported health, Vulnerable Elder Score and several demographic characteristics were associated with these preferences.ResultsData were collected from 8308 of 11 620 possible participants. Ninety-seven per cent of respondents wanted doctors to offer them choices and to consider their opinions. However, two out of three (67%) preferred to leave medical decisions to the doctor. In multiple regression analyses, preferring to leave decisions to the doctor was associated with older age (per year, OR=1.019, 95% CI 1.003 to 1.036) and frequently attending religious services (OR=1.5, 95% CI 1.1 to 2.1, compared with never), and it was inversely associated with female sex (OR=0.6, 95% CI 0.5 to 0.8), university education (OR=0.6, 95% CI 0.4 to 0.9, compared with no high school diploma) and poor health (OR=0.6, 95% CI 0.3 to 0.9).ConclusionsAlmost all patients want doctors to offer them choices and to consider their opinions, but most prefer to leave medical decisions to the doctor. Patients who are male, less educated, more religious and healthier are more likely to want to leave decisions to their doctors, but effects are small.
A Novel Tumor Antigen Derived from Enhanced Degradation of Bax Protein in Human Cancers
Authors: Nunes Cláudia Trindade , Miners Kelly L. , Dolton Garry , Pepper Chris , Fegan Chris , Mason Malcolm D. , Man Stephen 
Published: June 2011

AbstractCancer cells frequently exhibit defects in apoptosis, which contribute to increased survival and chemotherapeutic resistance. For example, genetic mutations or abnormal proteasomal degradation can reduce expression of Bax which limits apoptosis. In cancers where abnormal proteasomal degradation of Bax occurs, we hypothesized that Bax peptides that bind to human leukocyte antigen (HLA) class I molecules would be generated for presentation to CD8+ T cells. To test this hypothesis, we generated T cells against pooled Bax peptides, using the blood of healthy human donors. Although T-cell responses were of low frequency (0.15%), a CD8+ T-cell clone (KSIVB17) was isolated that optimally recognized Bax136–144 peptide (IMGWTLDFL) presented by HLA-A*0201. KSIVB17 was able to recognize and kill a variety of HLA-matched cancer cells including primary tumor cells from chronic lymphocytic leukemia (CLL). No reactivity was seen against HLA-matched, nontransformed cells such as PHA blasts and skin fibroblasts. Furthermore, KSIVB17 reactivity corresponded with the proteasomal degradation patterns of Bax protein observed in cancer cells. Taken together, our findings suggest a new concept for tumor antigens based on regulatory proteins that are ubiquitously expressed in normal cells, but that have abnormally enhanced degradation in cancer cells. Bax degradation products offer candidate immune antigens in cancers such as CLL in which increased Bax degradation correlates with poor clinical prognosis. Cancer Res; 71(16); 5435–44. ©2011 AACR.
How Much Can A Priori Hydrologic Model Predictability Help in Optimal Merging of Satellite Precipitation Products?
Authors: Gebregiorgis Abebe , Hossain Faisal 
Published: June 2011

AbstractIn this study, the authors ask the question: Can a more superior precipitation product be developed by merging individual products according to their a priori hydrologic predictability? The performance of three widely used high-resolution satellite precipitation products [Tropical Rainfall Measuring Mission (TRMM) real-time precipitation product 3B42 (3B42-RT), the NOAA/Climate Prediction Center morphing technique (CMORPH), and Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks-Cloud Classification System (PERSIANN-CCS)] was evaluated in terms streamflow predictability for the entire Mississippi River basin using the Variable Infiltration Capacity (VIC) macroscale hydrologic model. A merging concept that was not based on a single universal merging formula for the whole basin but rather used a “localized” (grid box by grid box) approach for merging precipitation products was then explored. In this merging technique, the a priori (historical) hydrologic predictive skill of each product for each grid box was first identified. Prior to streamflow routing, the corresponding accuracy of the spatially distributed simulations of soil moisture and runoff were used as proxy for weights in merging the precipitation products. It was found that the merged product derived on the basis of runoff predictability outperformed its counterpart merged product derived on the basis of soil moisture simulation. Results indicate that such a grid box by grid box merging concept that leverages a priori information on predictability of individual products has the potential to yield a more superior product for streamflow prediction than what the individual products can deliver for hydrologic prediction.
Visual Search Asymmetries in Heavy Clutter: Implications for Display Design
Authors: Yamani Yusuke , McCarley Jason S. 
Published: June 2011

Objective: An experiment aimed to test whether design of symbology to produce visual search asymmetries might facilitate target detection in cluttered displays. Background: A visual search asymmetry exists between two stimuli when a target of one type is found efficiently among distractors of the second type but a target of the second type is found with difficulty among distractors of the first type. Asymmetries have generally been studied within relatively sparse displays. In the present study, the authors tested whether an asymmetry driven by stimulus familiarity persists within heavily cluttered imagery. Method: In this study, 10 participants performed a visual search task using stimuli (canonical vs. reversed Ns) known to produce a search asymmetry. Search stimuli were embedded within geospatial images containing either low or high levels of clutter. A decision theoretic index of sensitivity served as the dependent measure. Results: The search asymmetry was robust against the presence of heavy display clutter. Specifically, sensitivity was greater when the target was a reversed N rather than an N, and this pattern remained within cluttered displays. Time-accuracy analysis revealed that the search asymmetry increased the rate of information accumulation roughly equally within low- and high- clutter images. Conclusion: Search asymmetries are robust against heavy, spatially continuous visual clutter. Application: Design of display symbology to produce visual search asymmetries can offset the costs of visual clutter, maximizing detectability of task-critical information in complex displays.
Are we heading in the same direction? European and African doctors’ and nurses’ views and experiences regarding outcome measurement in palliative care
Authors: Daveson BA , Simon ST , Benalia H , Downing J , Higginson IJ , Harding R , Bausewein C ,   on behalf of PRISMA
Published: June 2011

Objective: To examine and compare doctors’ and nurses’ views and experiences regarding outcome measurement in palliative care, including patient-reported outcome measures (PROMs). Methods: A web-based survey developed through expert review and piloting was conducted in Europe and Africa with palliative care professionals working in clinical care, audit and research. Results: The overall participation rate was 42% (663/1592) and the overall completion rate was 59% (392/663). Of these respondents, 196 were doctors (51% male, mean 47 years) and 104 were nurses (84% female, mean 45 years). Doctors’ most common reported reasons for not using tools were time constraints followed by lack of training. For nurses, it was lack of training followed by time constraints. Provision of information and guidance influenced willingness to use measures. For those that used tools, most reported favourable outcome measurement experiences. Both prioritized brief PROMs, and measures that included physical and psychological domains. For clinical purposes, the main advantage for doctors was assessment/screening, and clinical decision making for nurses. For research, doctors were most influenced by a measure’s comparability with national/international literature followed by its validation in palliative care. For nurses, validation in palliative care was followed by tool access. Conclusion: Overall these respondents shared similar views and experiences, and both were influenced by similar factors. Multidisciplinary outcome measurement education and training is feasible and required. Multidimensional and brief PROMs that include physical and psychological domains need to be prioritized, and access to freely available, validated and translated tools is needed to ensure cross-national comparisons and coordination of international research.
What is the methodological rigour of palliative care research in long-term care facilities in Europe? A systematic review
Authors: Albers Gwenda , Harding Richard , Pasman H Roeline W , Onwuteaka-Philipsen Bregje D , Hall Sue , Toscani Franco , Ribbe Miel W , Deliens Luc ,   On behalf of PRISMA
Published: June 2011

Background: The European population is rapidly ageing, resulting in increasing numbers of older people dying in long-term care facilities. There is an urgent need for palliative care in long-term care facilities. Aim: The aim of this study was to systematically review the literature on palliative care research in long-term care facilities in Europe with respect to how the palliative care populations were described, and to determine the study designs and patient outcome measures utilized. Methods: We used a systematic literature review. The search strategy included searches of PubMed, Embase and PsychINFO databases from 2000 up to May 2010, using search terms related to ‘palliative care’ and ‘end-of-life care’ combined with search terms related to ‘long-term care’. We selected articles that reported studies on patient outcome data of palliative care populations residing in a long-term care facility in Europe. Results: This review demonstrated that there are few, and mainly descriptive, European studies on palliative care research in long-term care facilities. Fourteen studies were retained in the review, of which eight were conducted in the Netherlands. None of these studies described their study population specifically as a palliative care or end-of-life care population. Retrospective and prospective designs were applied using many different measurement instruments. Most instruments were proxy ratings. Symptom (management) was the most frequently measured outcome. Conclusion: To improve future research on palliative care in long-term care facilities, agreement on what can be considered as palliative care in long-term care facilities and, the availability of well-developed and tested measurement instruments is needed to provide more evidence, and to make future research more comparable.
An uncertain future: The unchanging views of care home residents about living and dying
Authors: Mathie Elspeth , Goodman Claire , Crang Clare , Froggatt Katherine , Iliffe Steve , Manthorpe Jill , Barclay Stephen 
Published: June 2011

Background: Older people living in a care home have a limited life expectancy, and care homes are an important setting for end-of-life care provision. Aim: This research aimed to explore the views, experiences and expectations of end-of-life care among care home residents to understand if key events or living in a residential environment influenced their views. Design: The research used a prospective design. The paper draws on the qualitative interviews of 63 care home residents who were interviewed up to three times over a year. This was a sub-sample of the larger data set of 121 care home residents. Setting/Participants: The residents were recruited from six care homes (providing personal care with no on-site nursing) in the UK. Results: Four main themes were identified; Living in the Past, Living in the Present, Thinking about the Future and Actively Engaged with planning the future. Many residents said they had not spoken to the care staff about end-of-life care; many assumed their family or General Practitioner would take responsibility. Conclusions: Core to the older person’s ability to discuss end-of-life care is their acceptance of being in a care home, the involvement of family members in making decisions and the extent to which they believed they could influence decision making within their everyday lives. Advance care plans should document ongoing dialogue. These findings can inform how primary health and palliative care services introduce, discuss and tailor existing frameworks and programmes of end-of-life care.