bluuebunny/crossref_metadata_2025_split huggingface dataset:
Social Policy Preferences and Party Choice in the 2011 Swiss Elections
Authors: Fossati Flavia , Häusermann Silja 
Published: July 2014

AbstractTo what extent do social policy preferences explain party choice? This question has received little attention over the past years, because the bulk of the literature has argued that electoral choice is increasingly shaped by identity‐based attitudes, rather than by preferences for economic‐distributive social policies. We argue that in the wake of this debate, the significance of social policy preferences for electoral choice has been underestimated, because most contributions neglect social policy debates that are specific to post‐industrial societies. In particular, they merely focus on income redistribution, while neglecting distributive conflicts around social investment. The Selects 2011 data allows investigating this crucial distinction for Switzerland. Our empirical analyses confirm that it is pivotal to take the pluridimensionality of distributive conflicts seriously: when looking at preferences for social investment rather than income redistribution, we find that social policy preferences are significant explanatory factors for the choice of the five major Swiss political parties.
Electoral Competition and the New Class Cleavage
Authors: Goldberg Andreas C. , Sciarini Pascal 
Published: July 2014

AbstractThe class cleavage has been the most important structuring force in most West European countries. In the last decades, the question regarding whether the social class still influences voting behavior has been intensively debated. One strand of literature suggests a transformation of the old class divide into a new – or reformulated – class cleavage. However, there is still little empirical evidence about the circumstances under which this new divide may become important. The present paper contributes to fill this gap, by analyzing in how far electoral competition conditions the strength of the new class cleavage. Applying data from the Swiss National Elections 2007 and 2011 to a comparative analysis across cantons we find that the impact of the new class cleavage on electoral choice varies according to party system polarization. The proportionality of the electoral system, by contrast, does not have a clear conditional effect.
Disseminated histoplasmosis in allogeneic bone marrow transplant: a diagnosis not to be missed
Authors: Haydoura S. , Wallentine J. , Lopansri B. , Ford C.D. , Saad D. , Burke J.P. 
Published: July 2014

AbstractImmunosuppressed patients are at highest risk for disseminated histoplasmosis, but only a few cases have been reported in hematopoietic stem cell transplant recipients. We report a case of disseminated histoplasmosis in an allogeneic bone marrow transplant recipient residing in a non‐endemic area. Diagnosis was first suspected based on a peripheral blood smear.
The association of the Thr715Pro P‐selectin genotype with levels of P‐selectin in platelet concentrates
Authors: Jilma‐Stohlawetz P. , Mannhalter C. , Kaider A. , Waidacher T. , Jilma B. , Panzer S. 
Published: July 2014

Background and ObjectivesP‐selectin is stored in the alpha granules of platelets and in the Weibel Palade bodies of endothelial cells; upon activation, it is translocated to the cell surface and released into the plasma in soluble form. One variant of the P‐selectin gene, the Thr715Pro polymorphism, is strongly associated with the plasma levels of soluble P‐selectin. In platelet concentrates soluble P‐selectin can be regarded mainly platelet derived.Materials and MethodsThe relation of the genotype with soluble P‐selectin, platelet expressed P‐selectin and the sum of all forms of P‐selectin – comprising soluble P‐selectin, platelet surface P‐selectin and P‐selectin from the alpha granules – was assessed in fresh whole blood and in apheresis platelets suspended in 35% plasma/65% SSP+ obtained from 89 platelet donors.ResultsLevels of total P‐selectin were genotype associated (P = 0·025); likewise, in fresh whole blood there was an association of soluble P‐selectin with genotype (P = 0·02). In platelets suspended in additive solution, however, levels of the storage‐associated or TRAP‐6 agonist induced increase of platelets' P‐selectin were not associated with the genotype. A correlation between levels of soluble P‐selectin and surface expression of P‐selectin was observed on day 3 of storage in Thr715Thr individuals (P < 0·0001), but not in heterozygotes (Thr715Pro, P = 0·2).ConclusionThe donors' genotype has only little influence on levels of soluble P‐selectin in apheresis platelets suspended in 35% plasma/65% SSP+.
Magnetic resonance imaging: a tool to monitor and optimize enzyme distribution during porcine pancreas distention for islet isolation
Authors: Scott William E. , Weegman Bradley P. , Balamurugan Appakalai N. , Ferrer‐Fabrega Joana , Anazawa Takayuki , Karatzas Theodore , Jie Tun , Hammer Bruce E. , Matsumoto Shuchiro , Avgoustiniatos Efstathios S. , Maynard Kristen S. , Sutherland David E. R. , Hering Bernhard J. , Papas Klearchos K. 
Published: July 2014

AbstractPorcine islet xenotransplantation is emerging as a potential alternative for allogeneic clinical islet transplantation. Optimization of porcine islet isolation in terms of yield and quality is critical for the success and cost‐effectiveness of this approach. Incomplete pancreas distention and inhomogeneous enzyme distribution have been identified as key factors for limiting viable islet yield per porcine pancreas. The aim of this study was to explore the utility of magnetic resonance imaging (MRI) as a tool to investigate the homogeneity of enzyme delivery in porcine pancreata. Traditional and novel methods for enzyme delivery aimed at optimizing enzyme distribution were examined. Pancreata were procured from Landrace pigs via en bloc viscerectomy. The main pancreatic duct was then cannulated with an 18‐g winged catheter and MRI performed at 1.5‐T. Images were collected before and after ductal infusion of chilled MRI contrast agent (gadolinium) in physiological saline. Regions of the distal aspect of the splenic lobe and portions of the connecting lobe and bridge exhibited reduced delivery of solution when traditional methods of distention were utilized. Use of alternative methods of delivery (such as selective re‐cannulation and distention of identified problem regions) resolved these issues, and MRI was successfully utilized as a guide and assessment tool for improved delivery. Current methods of porcine pancreas distention do not consistently deliver enzyme uniformly or adequately to all regions of the pancreas. Novel methods of enzyme delivery should be investigated and implemented for improved enzyme distribution. MRI serves as a valuable tool to visualize and evaluate the efficacy of current and prospective methods of pancreas distention and enzyme delivery.
The Proteasome-Ubiquitin System Is Required for Efficient Killing of Intracellular Streptococcus pneumoniae by Brain Endothelial Cells
Authors: Iovino Federico , Gradstedt Henrik , Bijlsma Jetta J. 
Published: July 2014

ABSTRACT

Streptococcus pneumoniae
(pneumococcus) is a Gram-positive bacterium that causes serious invasive diseases, such as pneumonia, bacteremia, and meningitis, with high morbidity and mortality throughout the world. Before causing invasive disease,
S. pneumoniae
encounters cellular barriers, which are often composed of endothelial cells, like the alveolar-capillary barrier and the blood-brain barrier.
S. pneumoniae
adheres to endothelial cells and may invade them, which requires an efficient host response to the intracellular bacteria. The precise intracellular fate of
S. pneumoniae
during infection still remains a subject of debate. The proteasome-ubiquitin system is largely responsible for the degradation of misfolded, damaged, or no-longer-useful proteins. Recently, the role of the proteasome-ubiquitin system in the clearing of invading bacteria and viruses has been more closely studied. In this study, we show that inhibition of the proteasome-ubiquitin system leads to a marked increase in
S. pneumoniae
survival inside host cells. Immunofluorescence analysis showed that intracellular pneumococci colocalized with proteasome and ubiquitin in human endothelial cells
in vitro
. Confocal imaging analysis demonstrated that in the brains of mice intravenously infected with
S. pneumoniae
, the bacteria were inside endothelial cells, where they colocalized with proteasome and ubiquitin signals. In conclusion, our data indicate that a fully functional proteasome-ubiquitin system in endothelial cells is crucial for efficient killing of intracellular
S. pneumoniae
.

IMPORTANCE
Bacterial meningitis is a serious invasive disease with high morbidity and mortality. How bacteria traverse the blood-brain barrier
in vivo
and what mechanisms are employed by the host to prevent invasion are still unclear. Our data show that inhibition of the proteasome-ubiquitin system
in vitro
leads to a significant increase in
S. pneumoniae
survival inside brain endothelial cells. Confocal imaging analysis of brain tissue from mice intravenously infected with pneumococci demonstrated that the bacteria are inside brain microvascular endothelial cells, where they associate with the proteasome and ubiquitin. This is, as far as we know, the first report that demonstrates that
Streptococcus pneumoniae
invades endothelial cells of the blood-brain barrier
in vivo
. The host requires the proteasome-ubiquitin system for an efficient decimation of intracellular
S. pneumoniae.
Murine AKAP7 Has a 2′,5′-Phosphodiesterase Domain That Can Complement an Inactive Murine Coronavirus ns2 Gene
Authors: Gusho Elona , Zhang Rong , Jha Babal K. , Thornbrough Joshua M. , Dong Beihua , Gaughan Christina , Elliott Ruth , Weiss Susan R. , Silverman Robert H. 
Published: July 2014

ABSTRACTViral 2′,5′-phosphodiesterases (2′,5′-PDEs) help disparate RNA viruses evade the antiviral activity of interferon (IFN) by degrading 2′,5′-oligoadenylate (2-5A) activators of RNase L. A kinase anchoring proteins (AKAPs) bind the regulatory subunits of protein kinase A (PKA) to localize and organize cyclic AMP (cAMP) signaling during diverse physiological processes. Among more than 43 AKAP isoforms, AKAP7 appears to be unique in its homology to viral 2′,5′-PDEs. Here we show that mouse AKAP7 rapidly degrades 2-5A with kinetics similar to that of murine coronavirus (mouse hepatitis virus [MHV]) strain A59 ns2 and human rotavirus strain WA VP3 proteins. To determine whether AKAP7 could substitute for a viral 2′,5′-PDE, we inserted AKAP7 cDNA into an MHV genome with an inactivated ns2 gene. The AKAP7 PDE domain or N-terminally truncated AKAP7 (both lacking a nuclear localization motif), but not full-length AKAP7 or a mutant, AKAP7H185R, PDE domain restored the infectivity of ns2 mutant MHV in bone marrow macrophages and in livers of infected mice. Interestingly, the AKAP7 PDE domain and N-terminally deleted AKAP7 were present in the cytoplasm (the site of MHV replication), whereas full-length AKAP7 was observed only in nuclei. We suggest the possibility that viral acquisition of the host AKAP7 PDE domain might have occurred during evolution, allowing diverse RNA viruses to antagonize the RNase L pathway.IMPORTANCEEarly virus-host interactions determine whether an infection is established, highlighting the need to understand fundamental mechanisms regulating viral pathogenesis. Recently, our laboratories reported a novel mode of regulation of the IFN antiviral response. We showed that the coronavirus MHV accessory protein ns2 antagonizes the type I IFN response, promoting viral replication and hepatitis. ns2 confers virulence by cleaving 2′,5′-oligoadenylate (2-5A) activators of RNase L in macrophages. We also reported that the rotavirus VP3 C-terminal domain (VP3-CTD) cleaves 2-5A and that it may rescue ns2 mutant MHV. Here we report that a cellular protein, AKAP7, has an analogous 2′,5′-phosphodiesterase (2′,5′-PDE) domain that is able to restore the growth of chimeric MHV expressing inactive ns2. The proviral effect requires cytoplasmic localization of the AKAP7 PDE domain. We speculate that AKAP7 is the ancestral precursor of viral proteins, such as ns2 and VP3, that degrade 2-5A to evade the antiviral activity of RNase L.
Conservation of Transcription Start Sites within Genes across a Bacterial Genus
Authors: Shao Wenjun , Price Morgan N. , Deutschbauer Adam M. , Romine Margaret F. , Arkin Adam P. 
Published: July 2014

ABSTRACT

Transcription start sites (TSSs) lying inside annotated genes, on the same or opposite strand, have been observed in diverse bacteria, but the function of these unexpected transcripts is unclear. Here, we use the metal-reducing bacterium
Shewanella oneidensis
MR-1 and its relatives to study the evolutionary conservation of unexpected TSSs. Using high-resolution tiling microarrays and 5′-end RNA sequencing, we identified 2,531 TSSs in
S. oneidensis
MR-1, of which 18% were located inside coding sequences (CDSs). Comparative transcriptome analysis with seven additional
Shewanella
species revealed that the majority (76%) of the TSSs within the upstream regions of annotated genes (gTSSs) were conserved. Thirty percent of the TSSs that were inside genes and on the sense strand (iTSSs) were also conserved. Sequence analysis around these iTSSs showed conserved promoter motifs, suggesting that many iTSS are under purifying selection. Furthermore, conserved iTSSs are enriched for regulatory motifs, suggesting that they are regulated, and they tend to eliminate polar effects, which confirms that they are functional. In contrast, the transcription of antisense TSSs located inside CDSs (aTSSs) was significantly less likely to be conserved (22%). However, aTSSs whose transcription was conserved often have conserved promoter motifs and drive the expression of nearby genes. Overall, our findings demonstrate that some internal TSSs are conserved and drive protein expression despite their unusual locations, but the majority are not conserved and may reflect noisy initiation of transcription rather than a biological function.

IMPORTANCE
The first step of gene expression is the initiation of transcription from promoters, which have been traditionally thought to be located upstream of genes. Recently, studies showed that in diverse bacteria, promoters are often located inside genes. It has not been clear if these unexpected promoters are important to the organism or if they result from transcriptional noise. Here, we identify and examine promoters in eight related bacterial species. Promoters that lie within genes on the sense strand are often conserved as locations and in their sequences. Furthermore, these promoters often affect the bacterium’s growth. Thus, many of these unexpected promoters are likely functional. Fewer promoters that lie within genes on the antisense strand are conserved, but the conserved ones seem to drive the expression of nearby genes.
What is the current NHS service provision for patients severely affected by chronic fatigue syndrome/myalgic encephalomyelitis? A national scoping exercise
Authors: McDermott Clare , Al Haddabi Atheer , Akagi Hiroko , Selby Michelle , Cox Diane , Lewith George 
Published: July 2014

BackgroundChronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), in its most severe clinical presentation, can result in patients becoming housebound and bedbound so unable to access most available specialist services. This presents particular clinical risks and treatment needs for which the National Institute for Health and Care Excellence (NICE) advises specialist medical care and monitoring. The extent of National Health Service (NHS) specialist provision in England for severe CFS/ME is currently unknown.ObjectivesTo establish the current NHS provision for patients with severe CFS/ME in England.Setting and participantsAll 49 English NHS specialist CFS/ME adult services in England, in 2013.MethodCross-sectional survey by email questionnaire.Primary outcome measuresAdherence to NICE guidelines for severe CFS/ME.ResultsAll 49 services replied (100%). 33% (16/49) of specialist CFS/ME services provided no service for housebound patients. 55% (27/49) services did treat patients with severe CFS/ME and their interventions followed the NICE guidelines. The remaining services (12%, 6/49) offered occasional or minimal support where funding allowed. There was one NHS unit providing specialist inpatient CFS/ME provision in England.ConclusionsStudy findings highlight substantial variation in access to specialist care for patients with severe presentation of CFS/ME. Where treatment was provided, this appeared to comply with NICE recommendations for this patient group.
Posterior circulation flow diversion: a single-center experience and literature review
Authors: Toth Gabor , Bain Mark , Hussain M Shazam , Moskowitz Shaye , Masaryk Thomas , Rasmussen Peter , Hui Ferdinand 
Published: July 2014

BackgroundFlow diverters have been used predominantly for large anterior circulation aneurysms. Data on the safety and efficacy of this treatment for posterior circulation aneurysms are limited.ObjectiveTo present our posterior circulation flow diverter experience, outcomes and morbidity in comparison with recent studies.MethodsA retrospective chart and imaging review of six patients with seven aneurysms in posterior circulation vessels, treated with flow diverter technology was carried out. A literature review was performed using standard online search tools.ResultsWe included five saccular and two fusiform posterior circulation aneurysms. An average of two flow diverters was placed for each patient. Adjunctive coiling was used in three cases. Follow-up at an average of 14.5 months showed complete angiographic occlusion in 4 (57.1%) cases, including one patient with in-stent thrombosis and major brainstem stroke at 4.5 months, a week after self-discontinuing dual antiplatelet therapy. Two other patients developed small periprocedural strokes but had excellent recovery. One death occurred 18 months after the initial procedure. No aneurysm rupture or parenchymal hemorrhage was seen. Overall, 5 (71%) cases, all with saccular aneurysms, had good clinical outcome (modified Rankin score (mRS) 0–1). Fusiform basilar aneurysms had markedly worse outcomes (mRS 5 and 6). Our literature review yielded six other studies with 100 additional patients. Overall, good outcome was seen in 74.3%, with a 12.3% average mortality and 11% permanent neurologic deficit rate. Complete occlusion varied from 43% to 100%.ConclusionsFlow diversion may be a possible treatment in carefully selected patients with high-risk atypical posterior circulation aneurysms, with poor natural history and no optimal treatment strategy. Symptomatic and fusiform large aneurysms appear to carry the highest risk. Further studies are necessary to assess the role of flow diversion in the posterior circulation.
Shifts of generators and delta sets of numerical monoids
Authors: Chapman S. T. , Kaplan Nathan , Lemburg Tyler , Niles Andrew , Zlogar Christina 
Published: July 2014

Let S be a numerical monoid with minimal generating set 〈n1, …, nt〉. For m ∈ S, if [Formula: see text], then [Formula: see text] is called a factorization length of m. We denote by ℒ(m) = {m1, …, mk} (where mi < mi+1 for each 1 ≤ i < k) the set of all possible factorization lengths of m. The Delta set of m is defined by Δ(m) = {mi+1 - mi | 1 ≤ i < k} and the Delta set of S by Δ(S) = ⋃m∈SΔ(m). In this paper, we expand on the study of Δ(S) begun in [C. Bowles, S. T. Chapman, N. Kaplan and D. Reiser, On delta sets of numerical monoids, J. Algebra Appl. 5 (2006) 1–24] in the following manner. Let r1, r2, …, rt be an increasing sequence of positive integers and Mn = 〈n, n + r1, n + r2, …, n + rt〉 a numerical monoid where n is some positive integer. We prove that there exists a positive integer N such that if n > N then |Δ(Mn)| = 1. If t = 2 and r1 and r2 are relatively prime, then we determine a value for N which is sharp.
MET-Mediated Resistance to EGFR Inhibitors: An Old Liaison Rooted in Colorectal Cancer Stem Cells
Authors: Boccaccio Carla , Luraghi Paolo , Comoglio Paolo M. 
Published: July 2014

Abstract
Inhibitors of EGFR are currently approved for the therapy of metastatic colorectal cancer (as well as other tumors), but their benefits are limited by inherent and acquired resistance, whose mechanisms are the subject of intense investigation. It is known that such resistance relies on a handful of genetic lesions and/or extracellular signals bypassing the requirement of EGF for cell proliferation and survival. As recently shown, these mechanisms may imply oncogenic activation of MET or its stimulation by the ligand hepatocyte growth factor. However, it is still largely obscure if sensitivity or resistance to EGFR inhibitors operates in cancer stem cells. Convincing evidence indicates that this elusive cell subpopulation is present at the roots of colorectal cancer. Conceivably, cancer stem cells accumulate the genetic lesions driving tumor onset and progression, as well as the genetic determinants of sensitivity or resistance to conventional and targeted therapies. Recent studies enlighten the expression of functional EGFR and MET in colorectal cancer stem cells and the outcome of their inhibition. Evidence is provided that, in patients sensitive to EGFR therapy, association of MET inhibitors fosters cancer stem cell eradication and durable tumor regression. Cancer Res; 74(14); 3647–51. ©2014 AACR.
Molecular Pathways: Deregulation of Histone H3 Lysine 27 Methylation in Cancer—Different Paths, Same Destination
Authors: Ezponda Teresa , Licht Jonathan D. 
Published: July 2014

Abstract
Methylation of lysine 27 on histone H3 (H3K27me), a modification associated with gene repression, plays a critical role in regulating the expression of genes that determine the balance between cell differentiation and proliferation. Alteration of the level of this histone modification has emerged as a recurrent theme in many types of cancer, demonstrating that either excess or lack of H3K27 methylation can have oncogenic effects. Cancer genome sequencing has revealed the genetic basis of H3K27me deregulation, including mutations of the components of the H3K27 methyltransferase complex PRC2 and accessory proteins, and deletions and inactivating mutations of the H3K27 demethylase UTX in a wide variety of neoplasms. More recently, mutations of lysine 27 on histone H3 itself were shown to prevent H3K27me in pediatric glioblastomas. Aberrant expression or mutations in proteins that recognize H3K27me3 also occur in cancer and may result in misinterpretation of this mark. In addition, due to the cross-talk between different epigenetic modifications, alterations of chromatin modifiers controlling H3K36me, or even mutations of this residue, can ultimately regulate H3K27me levels and distribution across the genome. The significance of mutations altering H3K27me is underscored by the fact that many tumors harboring such lesions often have a poor clinical outcome. New therapeutic approaches targeting aberrant H3K27 methylation include small molecules that block the action of mutant EZH2 in germinal center-derived lymphoma. Understanding the biologic consequences and gene expression pathways affected by aberrant H3K27 methylation may also lead to other new therapeutic strategies. Clin Cancer Res; 20(19); 5001–8. ©2014 AACR.