bluuebunny/crossref_metadata_2025_split huggingface dataset:
Guinea Pig Prion Protein Supports Rapid Propagation of Bovine Spongiform Encephalopathy and Variant Creutzfeldt-Jakob Disease Prions
Authors: Watts Joel C. , Giles Kurt , Saltzberg Daniel J. , Dugger Brittany N. , Patel Smita , Oehler Abby , Bhardwaj Sumita , Sali Andrej , Prusiner Stanley B. 
Published: July 2016

ABSTRACT

The biochemical and neuropathological properties of bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) prions are faithfully maintained upon transmission to guinea pigs. However, primary and secondary transmissions of BSE and vCJD in guinea pigs result in long incubation periods of ∼450 and ∼350 days, respectively. To determine if the incubation periods of BSE and vCJD prions could be shortened, we generated transgenic (Tg) mice expressing guinea pig prion protein (GPPrP). Inoculation of Tg(GPPrP) mice with BSE and vCJD prions resulted in mean incubation periods of 210 and 199 days, respectively, which shortened to 137 and 122 days upon serial transmission. In contrast, three different isolates of sporadic CJD prions failed to transmit disease to Tg(GPPrP) mice. Many of the strain-specified biochemical and neuropathological properties of BSE and vCJD prions, including the presence of type 2 protease-resistant PrP
Sc
, were preserved upon propagation in Tg(GPPrP) mice. Structural modeling revealed that two residues near the N-terminal region of α-helix 1 in GPPrP might mediate its susceptibility to BSE and vCJD prions. Our results demonstrate that expression of GPPrP in Tg mice supports the rapid propagation of BSE and vCJD prions and suggest that Tg(GPPrP) mice may serve as a useful paradigm for bioassaying these prion isolates.

IMPORTANCE
Variant Creutzfeldt-Jakob disease (vCJD) and bovine spongiform encephalopathy (BSE) prions are two of the prion strains most relevant to human health. However, propagating these strains in mice expressing human or bovine prion protein has been difficult because of prolonged incubation periods or inefficient transmission. Here, we show that transgenic mice expressing guinea pig prion protein are fully susceptible to vCJD and BSE prions but not to sporadic CJD prions. Our results suggest that the guinea pig prion protein is a better, more rapid substrate than either bovine or human prion protein for propagating BSE and vCJD prions.
An RNA Element That Facilitates Programmed Ribosomal Readthrough in Turnip Crinkle Virus Adopts Multiple Conformations
Authors: Kuhlmann Micki M. , Chattopadhyay Maitreyi , Stupina Vera A. , Gao Feng , Simon Anne E. 
Published: July 2016

ABSTRACT

Ribosome recoding is used by RNA viruses for translational readthrough or frameshifting past termination codons for the synthesis of extension products. Recoding sites, along with downstream recoding stimulatory elements (RSEs), have long been studied in reporter constructs, because these fragments alone mediate customary levels of recoding and are thus assumed to contain complete instructions for establishment of the proper ratio of termination to recoding. RSEs from the
Tombusviridae
and
Luteoviridae
are thought to be exceptions, since they contain a long-distance RNA-RNA connection with the 3′ end. This interaction has been suggested to substitute for pseudoknots, thought to be missing in tombusvirid RSEs. We provide evidence that the phylogenetically conserved RSE of the carmovirus
Turnip crinkle virus
(TCV) adopts an alternative, smaller structure that extends an upstream conserved hairpin and that this alternative structure is the predominant form of the RSE within nascent viral RNA in plant cells and when RNA is synthesized
in vitro
. The TCV RSE also contains an internal pseudoknot along with the long-distance interaction, and the pseudoknot is not compatible with the phylogenetically conserved structure. Conserved residues just past the recoding site are important for recoding, and these residues are also conserved in the RSEs of gammaretroviruses. Our data demonstrate the dynamic nature of the TCV RSE and suggest that studies using reporter constructs may not be effectively recapitulating RSE-mediated recoding within viral genomes.

IMPORTANCE
Ribosome recoding is used by RNA viruses to enable ribosomes to extend translation past termination codons for the synthesis of longer products. Recoding sites and a downstream recoding stimulatory element (RSE) mediate expected levels of recoding when excised and placed in reporter constructs and thus are assumed to contain complete instructions for the establishment of the proper ratio of termination to recoding. We provide evidence that most of the TCV RSE adopts an alternative structure that extends an upstream conserved hairpin and that this alternative structure, and not the phylogenetically conserved structure, is the predominant form of the RSE in RNA synthesized
in vitro
and in plant cells. The TCV RSE also contains an internal pseudoknot that is not compatible with the phylogenetically conserved structure and an RNA bridge to the 3′ end. These data suggest that the TCV RSE is structurally dynamic and that multiple conformations are likely required to regulate ribosomal readthrough.
Simulations in undergraduate nursing programmes in New Zealand: current status and next steps
Authors: Lesa Raewyn , Daniel Ben 
Published: July 2016

IntroductionThere is an increasing global tendency to use simulations in nursing education. This research examined the current status of simulation programs in undergraduate nursing schools in New Zealand. The goal was to gain a better understanding of how simulations are currently implemented in nursing schools and to identify the associated opportunities and challenges.Methods16 nursing schools in New Zealand deliver undergraduate nursing education. 10 of these schools selected a nursing leader who was involved in the schools’ simulation program to complete an online survey. The survey questions were designed to explore the nature of simulations in nursing schools, and the opportunities and challenges experienced in the implementation of these programmes.Data analysisSurvey data were analysed and presented as summary statistics (frequencies and percentages). Responses to short questions were thematically analysed and common themes were identified. The analysis was divided into demographic characterises and main results.ResultsThe key outcomes of the study have shown the prevalence of various simulation modalities in nursing schools in New Zealand. The analysis also suggests that the current practices associated with the integration of simulations into nursing education in New Zealand are fragmented and sporadic. Challenges shared across all institutions include inadequate resourcing of simulation programs, poor curriculum integration and programme alignment; a lack of shared understanding of what constitutes simulation and the extent to which simulation modalities achieve learning outcomes.ConclusionsThe outcome of this study has contributed to a better understanding of the prevalence and nature of simulation programs in undergraduate nursing schools in New Zealand. It has also provided insights into the different opportunities and challenges associated with implementing these programmes in nursing schools. Furthermore, the research has identified important conceptual and theoretical issues related to the broad discourse on the use of simulations in undergraduate nursing education.
Exosome-mediated Transfer of αvβ3 Integrin from Tumorigenic to Nontumorigenic Cells Promotes a Migratory Phenotype
Authors: Singh Amrita , Fedele Carmine , Lu Huimin , Nevalainen Marja T. , Keen James H. , Languino Lucia R. 
Published: July 2016

Abstract
The αvβ3 integrin is known to be highly upregulated during cancer progression and promotes a migratory and metastatic phenotype in many types of tumors. We hypothesized that the αvβ3 integrin is transferred through exosomes and, upon transfer, has the ability to support functional aberrations in recipient cells. Here, for the first time, it is demonstrated that αvβ3 is present in exosomes released from metastatic PC3 and CWR22Pc prostate cancer cells. Exosomal β3 is transferred as a protein from donor to nontumorigenic and tumorigenic cells as β3 protein or mRNA levels remain unaffected upon transcription or translation inhibition in recipient cells. Furthermore, it is shown that upon exosome uptake, de novo expression of an αvβ3 increases adhesion and migration of recipient cells on an αvβ3 ligand, vitronectin. To evaluate the relevance of these findings, exosomes were purified from the blood of TRAMP mice carrying tumors where the expression of αvβ3 is found higher than in exosomes from wild-type mice. In addition, it is demonstrated that αvβ3 is coexpressed with synaptophysin, a biomarker for aggressive neuroendocrine prostate cancer.
Implications: Overall this study reveals that the αvβ3 integrin is transferred from tumorigenic to nontumorigenic cells via exosomes, and its de novo expression in recipient cells promotes cell migration on its ligand. The increased expression of αvβ3 in exosomes from mice bearing tumors points to its clinical relevance and potential use as a biomarker. Mol Cancer Res; 14(11); 1136–46. ©2016 AACR.
Experimental Validation of Noninvasive Epicardial and Endocardial Activation Imaging
Authors: Oosterhoff Peter , Meijborg Veronique M.F. , van Dam Peter M. , van Dessel Pascal F.H.M. , Belterman Charly N.W. , Streekstra Geert J. , de Bakker Jacques M.T. , Coronel Ruben , Oostendorp Thom F. 
Published: July 2016

Background—
Noninvasive imaging of cardiac activation before ablation of the arrhythmogenic substrate can reduce electrophysiological procedure duration and help choosing between an endocardial or epicardial approach. A noninvasive imaging technique was evaluated that estimates both endocardial and epicardial activation from body surface potential maps. We performed a study in isolated and in situ pig hearts, estimating activation from body surface potential maps during sinus rhythm and localizing endocardial and epicardial stimulation sites.

Methods and Results—
From 3 Langendorff-perfused pig hearts, 180 intramural unipolar electrograms were recorded during sinus rhythm and ectopic activation, together with pseudo–body surface potential map ECGs in 2 of them. From 4 other anesthetized pigs, 64-lead body surface potential maps were recorded during sinus rhythm and ventricular stimulation from 27 endocardial and epicardial sites. The ventricular activation pattern was computed from the recorded QRS complexes. For both Langendorff-perfused hearts, the calculated epicardial and endocardial activation patterns showed good qualitative correspondence to the patterns obtained with needle electrodes. Absolute timing difference for sinus rhythm was 10±5 and 11±8 ms respectively, and for ectopic activation 6±5 and 7±6 ms, respectively. Calculated activation for the in situ hearts in sinus rhythm was similar to patterns recorded in Langendorff-perfused hearts. During stimulation, the distance between the stimulation site and calculated site of earliest activation was 18 (15–27) mm, and 23 of 27 stimulation sites were correctly mapped to either endocardium or epicardium.

Conclusions—
Noninvasive activation imaging is able to determine earliest ventricular activation and discriminate endocardial from epicardial origin of activation with clinically relevant accuracy.
North Atlantic Storm-Track Sensitivity to Projected Sea Surface Temperature: Local versus Remote Influences
Authors: Ciasto Laura M. , Li Camille , Wettstein Justin J. , Kvamstø Nils Gunnar 
Published: July 2016

Abstract
This study investigates the sensitivity of the North Atlantic storm track to future changes in local and global sea surface temperature (SST) and highlights the role of SST changes remote to the North Atlantic. Results are based on three related coupled climate models: the Community Climate System Model, version 4 (CCSM4), the Community Earth System Model, version 1 (Community Atmosphere Model, version 5) [CESM1(CAM5)], and the Norwegian Earth System Model, version 1 (intermediate resolution) (NorESM1-M). Analysis reveals noticeable intermodel differences in projected storm-track changes from the coupled simulations [i.e., the difference in 200-hPa eddy activity between the representative concentration pathway 8.5 (RCP8.5) and historical scenarios]. In the CCSM4 coupled simulations, the North Atlantic storm track undergoes a poleward shift and eastward extension. In CESM1(CAM5), the storm-track change is dominated by an intensification and eastward extension. In NorESM1-M, the storm-track change is characterized by a weaker intensification and slight eastward extension. Atmospheric experiments driven only by projected local (North Atlantic) SST changes from the coupled models fail to reproduce the magnitude and structure of the projected changes in eddy activity aloft and zonal wind from the coupled simulations. Atmospheric experiments driven by global SST and sea ice changes do, however, reproduce the eastward extension. Additional experiments suggest that increasing greenhouse gas (GHG) concentrations do not directly influence storm-track changes in the coupled simulations, although they do through GHG-induced changes in SST. The eastward extension of the North Atlantic storm track is hypothesized to be linked to western Pacific SST changes that influence tropically forced Rossby wave trains, but further studies are needed to isolate this mechanism from other dynamical adjustments to global warming.
Clinical Outcomes of Hip Arthroscopy in Radiographically Diagnosed Retroverted Acetabula
Authors: Hartigan David E. , Perets Itay , Walsh John P. , Close Mary R. , Domb Benjamin G. 
Published: July 2016

Background: Symptomatic global retroversion of the acetabulum, as diagnosed on plain radiographs of the pelvis, has traditionally been treated with reverse periacetabular osteotomy, which improves posterior undercoverage and eliminates the anterior pincer lesion. There is a paucity of literature on hip arthroscopy in this group, secondary to theoretical concern of iatrogenic dysplasia, subsequent instability, and arthritis. Purpose: To evaluate the outcomes of hip arthroscopy for patients with a radiographic diagnosis of acetabular retroversion, using patient-reported outcomes, visual analog scale (VAS), patient satisfaction, and pre- and postoperative Tönnis grades. Study Design: Case series; Level of evidence, 4. Methods: Pre- and postoperative data were prospectively collected and retrospectively reviewed for patients who underwent hip arthroscopy at 1 institution between June 2008 and February 2012. Data were analyzed for patients who had adequate radiographs of the pelvis that demonstrated global acetabular retroversion and who were treated with arthroscopic surgery. Complications were tracked in this institution’s database. The modified Harris Hip Score, Nonarthritic Hip Score, Hip Outcome Score (HOS)–activities of daily living subscale, and HOS–sport-specific subscale, and VAS were analyzed preoperatively and at latest follow-up. Level of postoperative satisfaction was assessed on a scale of 0 to 10. Pre- and postoperative alpha angle, lateral center-edge angle, anterior center-edge angle, crossover percentage, and Tönnis grade were recorded. Tönnis grade at latest follow-up was utilized to determine progression of osteoarthritis. Results: A total of 82 hips among 78 patients were identified who met the listed criteria. The mean age of the patients was 23 years, and the mean follow-up was 39 months. These patients showed statistically significant improvement in modified Harris Hip Score (preoperative to ≥2-year follow-up: 65 to 81), Nonarthritic Hip Score (65 to 86), HOS–activities of daily living subscale (69 to 88), HOS–sport-specific subscale (47 to 76), and VAS (5.9 to 2.5) ( P < .0001). In terms of satisfaction with the surgery, they had an mean score of 7.4. There were 3 minor complications, none of which required reoperation. One patient underwent hip arthroplasty at 6 months after hip arthroscopy. Fifteen patients had >2-year radiographic follow-up; none of these patients had an increase in Tönnis grade as compared with the preoperative state. Conclusion: This study demonstrates that hip arthroscopy can successfully treat femoroacetabular impingement associated with a globally retroverted acetabulum at a minimum 2-year follow-up. Survivorship was 99% at 2 years, with 1 patient requiring further surgery in the form of hip arthroplasty. There was no noted progression of Tönnis grade at final follow-up. The procedure was extremely safe, with a minor complication rate of 3.6%.
CBFβ-SMMHC creates aberrant megakaryocyte-erythroid progenitors prone to leukemia initiation in mice
Authors: Cai Qi , Jeannet Robin , Hua Wei-Kai , Cook Guerry J. , Zhang Bin , Qi Jing , Liu Hongjun , Li Ling , Chen Ching-Cheng , Marcucci Guido , Kuo Ya-Huei 
Published: July 2016

Key Points
CM impairs erythroid lineage specification and differentiation from Pre-Meg/E progenitors. CM creates abnormal preleukemic Pre-Meg/E progenitors predisposed to leukemia initiation.
Model-based clustering with certainty estimation: implication for clade assignment of influenza viruses
Authors: Zhang Shunpu , Li Zhong , Beland Kevin , Lu Guoqing 
Published: July 2016

AbstractBackgroundClustering is a common technique used by molecular biologists to group homologous sequences and study evolution. There remain issues such as how to cluster molecular sequences accurately and in particular how to evaluate the certainty of clustering results.ResultsWe presented a model-based clustering method to analyze molecular sequences, described a subset bootstrap scheme to evaluate a certainty of the clusters, and showed an intuitive way using 3D visualization to examine clusters. We applied the above approach to analyze influenza viral hemagglutinin (HA) sequences. Nine clusters were estimated for high pathogenic H5N1 avian influenza, which agree with previous findings. The certainty for a given sequence that can be correctly assigned to a cluster was all 1.0 whereas the certainty for a given cluster was also very high (0.92–1.0), with an overall clustering certainty of 0.95. For influenza A H7 viruses, ten HA clusters were estimated and the vast majority of sequences could be assigned to a cluster with a certainty of more than 0.99. The certainties for clusters, however, varied from 0.40 to 0.98; such certainty variation is likely attributed to the heterogeneity of sequence data in different clusters. In both cases, the certainty values estimated using the subset bootstrap method are all higher than those calculated based upon the standard bootstrap method, suggesting our bootstrap scheme is applicable for the estimation of clustering certainty.ConclusionsWe formulated a clustering analysis approach with the estimation of certainties and 3D visualization of sequence data. We analysed 2 sets of influenza A HA sequences and the results indicate our approach was applicable for clustering analysis of influenza viral sequences.
Mexican immigration, occupational clustering, and the local labor market adjustment of African-American workers
Authors: Toussaint-Comeau Maude 
Published: July 2016

AbstractSince the 1970s, economic restructuring and shifts in industries have morphed the occupational path of workers, curbing socioeconomic mobility for many—wages of African-American workers which have trended upward in the 1960s and 1970s started stalling beginning in the 1980s. As Hispanic/Mexican immigrants were being absorbed in various industry sectors, researchers have questioned whether unfavorable trends in African-American wages and employment outcomes are tied to Mexican immigration. This paper examines the effect of Mexican immigrants on wages for African-Americans using various estimation methods and finds consistent negative estimates, pointing to an inverse relationship between Mexican immigrants and wages for African-Americans, which is consistent withcrowding outandsubstitution effects. However, in addition, analyses also show that a heavier source of depression of wages for African-Americans stems not just from immigration. In fact, in some ways, occupation clustering and specialization of Mexican immigrants mitigates impact of immigration on African-Americans on a whole range of low-skill occupations. But, all else equal, there appears rather to be a tendency for African-Americans to face an even greater “wage penalty” in more predominantly black occupations. The findings suggest that the interplay of immigration policy and workforce development policies and initiatives should be better understood as part of the conversation to redress factors preventing occupational and wage mobility of disadvantaged minority groups in the labor force.JEL Classification: J61, J62
HPV Testing of Self-Collected Vaginal Swabs for Cervical Cancer Prevention in South Africa
Authors: Kuhn Louise , Saidu Rakiya , Svanholm-Barrie Cecilia , Tergas Ana , Boa Rosalind , Moodley Jennifer , Wright Thomas C. , Persing David , Campbell Scott , Denny Lynette 
Published: July 2016

Abstract 33 Background: Cervical cancer screening programs in Low and Middle Income Countries (LMIC) need to be strengthened. One of the challenges is insufficient health care personnel to achieve optimal coverage. We evaluated the potential of human papillomavirus (HPV) testing using self-collected vaginal swabs to improve screening. Methods: As part of a larger NCI-supported study in Cape Town, South Africa, we recruited 261 HIV-uninfected and 237 HIV-infected women aged 30-60 years, at one primary health care site. All women were instructed to self-collect a vaginal swab on site immediately prior to a gynecologic exam, during which a cervical sample was collected. Both self- and clinician-collected samples were tested for high risk HPV types (16, 18, 45, 31, 33, 35, 52, 58, 51, 59, 39, 56, 66, 68) using Cepheid GeneXpert (HPV XpertTM). All women underwent at least one colposcopy with histological sampling. Classification of endpoint was based on expert pathology review. Results: The HPV prevalence using the cervical vs. self sample, respectively, was 14% vs. 25% among HIV-uninfected and 50% vs. 62% among HIV-infected women. Among women who were diagnosed with grade 2 or 3 cervical intraepithelial neoplasia (CIN) or cervical cancer, 94% were positive on HPV Xpert on the cervical and 88% on the vaginal swab, ignoring HIV status. However, specificity was poor for HPV tests done on self samples, 78% in HIV-uninfected and 52% in HIV-infected women. On a patient preference questionnaire, >90% of women stated they would be prepared to collect a sample at home and two-thirds expressed a preference to be examined by a clinician. Conclusion: Even in self-collected vaginal samples, HPV Xpert has excellent sensitivity for detecting cervical cancer precursor lesions. In LMIC settings where the ratio of health care workers to the population is low, HPV testing of self-collected samples could successfully triage women who require further evaluation and treatment. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: Louise Kuhn No relationship to disclose Rakiya Saidu No relationship to disclose Cecilia Svanholm-Barrie No relationship to disclose Ana Tergas Consulting or Advisory Role: Helomics Rosalind Boa No relationship to disclose Jennifer Moodley No relationship to disclose Thomas C. Wright No relationship to disclose David Persing No relationship to disclose Scott Campbell No relationship to disclose Lynette Denny No relationship to disclose