bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of human platelet antigen‐1a alloantibodies in cases of fetomaternal alloimmune thrombocytopenia using recombinant β3 integrin fragments coupled to fluorescently labeled beads
Authors: Chong Winnie , Metcalfe Paul , Mushens Rosey , Lucas Geoff , Ouwehand Willem H. , Navarrete Cristina V. 
Published: December 2010

BACKGROUND: Testing for alloantibodies against human platelet antigens (HPAs) is essential for the clinical diagnosis of fetomaternal alloimmune thrombocytopenia (FMAIT), posttransfusion purpura, and platelet (PLT) refractoriness. Most of the methods currently used for HPA alloantibody detection rely on the availability of panels of HPA‐typed PLTs and some rely on validated monoclonal antibodies (MoAbs) against the PLT glycoproteins. Recombinant β3 integrins displaying the HPA‐1a (rHPA‐1a) or HPA‐1b (rHPA‐1b) epitopes have been produced as an alternative source of antigen. The suitability of these integrin fragments was evaluated for the development of an HPA‐1a alloantibody screening assay, using Luminex xMAP technology.STUDY DESIGN AND METHODS: A 3‐plex bead assay was developed by coupling biotinylated rHPA‐1a, rHPA‐1b, and recombinant glycoprotein VI to LumAvidin microspheres. Forty patient samples referred for FMAIT diagnostic testing, which were previously screened by the MoAb‐specific immobilization of PLT antigens (MAIPA) assay, were used to assess the assay.RESULTS: The rHPA‐1a‐ and rHPA‐1b‐coupled beads were able to detect HPA‐1a and HPA‐1b alloantibodies in all patient samples tested that were previously confirmed to contain HPA‐1‐specific antibodies. Furthermore, HLA Class I antibodies did not cross‐react with the coupled beads.CONCLUSION: The 3‐plex bead assay can be used to detect HPA‐1a antibodies with sufficient specificity and sensitivity for use in the clinical setting of FMAIT. The development of other recombinant integrin fragments with the use of Luminex xMAP technology may assist in providing more rapid HPA antibody detection, enabling prompt diagnosis of alloimmune PLT disorders.
Validation Assessment of Risk Scores to Predict Postthrombolysis Intracerebral Haemorrhage
Authors: Cucchiara Brett , Kasner Scott , Tanne David , Levine Steven , Demchuk Andrew , Messe Steve , Sansing Lauren , Lees Kennedy , Lyden Patrick ,   for the SAINT Investigators
Published: December 2010

Background Two clinical risk scores, the Haemorrhage After Thrombolysis and Multicentre Stroke Survey scores, have been proposed to predict the risk of intracerebral haemorrhage following thrombolysis in acute ischaemic stroke. Aims To validate Haemorrhage After Thrombolysis and Multicentre Stroke Survey scores as predictors of post-tissue plasminogen activator symptomatic intracerebral haemorrhage and asymptomatic intracerebral haemorrhage in an independent cohort. Methods Haemorrhage After Thrombolysis and Multicentre Stroke Survey scores were calculated for the cohort of tissue plasminogen activator-treated patients enrolled in the placebo arms of the SAINT-I and SAINT-II trials. The absolute risk of symptomatic intracerebral haemorrhage and asymptomatic intracerebral haemorrhage associated with each scoring system was determined. The overall predictive value was assessed using c-statistics. Results Symptomatic intracerebral haemorrhage occurred in 5·6% of 965 patients treated with tissue plasminogen activator in the SAINT cohorts. The risk of symptomatic intracerebral haemorrhage was modestly greater, with higher Haemorrhage After Thrombolysis scores (0: 4·1%, 1: 4·1%, 2: 8·8%, 3: 12·5%, 4: 0%, 5: no subjects). Similar results were seen with the Multicentre Stroke Survey score (0: 0%, 1: 4·8%, 2: 2·3%, 3: 7·3%, 4: 6·3%). In logistic regression, the Haemorrhage After Thrombolysis score was associated with the risk of symptomatic intracerebral haemorrhage (odds ratio=1·41 per point, 95% confidence interval: 1·05–1·89, P=0·021) and asymptomatic intracerebral haemorrhage (odds ratio=1·59 per point, 95% confidence interval: 1·33–1·92, P<0·001). The Multicentre Stroke Survey score was modestly associated with the risk of symptomatic intracerebral haemorrhage (odds ratio=1·43 per point, 95% confidence interval: 0·95–2·15, P=0·084) and asymptomatic intracerebral haemorrhage (odds ratio=1·63 per point, 95% confidence interval: 1·27–2·08, P<0·001). The c-statistic was 0·59 for predicting symptomatic intracerebral haemorrhage and 0·61 for asymptomatic intracerebral haemorrhage for both the Haemorrhage After Thrombolysis and the Multicentre Stroke Survey scores. Conclusions While both the Haemorrhage After Thrombolysis and Multicentre Stroke Survey scores were associated with a risk of symptomatic intracerebral haemorrhage, discriminatory ability was limited.
MEMBRANE SEAL LEAKAGE IN NON‐FRACTURED CAPROCKS BY THE FORMATION OF OIL‐WET FLOW PATHS
Authors: Teige G.M.G. , Hermanrud C. , Rueslåtten H.G. 
Published: December 2010

Leakage through non‐fractured shaly caprock sequences is often envisioned as hydrocarbon percolation through water‐wet pore networks. Leakage by this process requires that the buoyancy of the hydrocarbon column overcomes the capillary entry pressure of the caprock pores. If it does not, then leakage through caprocks that are not hydrofractured depends on diffusion of hydrocarbons, which is an extremely slow process. As a result, the hydrocarbon residence time would be almost endless.We suggest a novel model for leakage through non‐fractured caprock shales. Two lines of laboratory‐based research motivate our suggestion. One of these addresses wettability alterations, while the other addresses pore‐scale fluid flow in the presence of capillary sealing. The latter approach has demonstrated that water can flow vertically through water‐wet oil reservoirs and further through caprocks, whereas the oil remains in the reservoir. This recognition is a consequence of the observation that residual water in the reservoir can be both continuous and mobile.We suggest that such flow of residual water through reservoirs and into caprocks can lead to the establishment of oil‐wet flow paths in membrane seals. This process takes place in a sequence of events that leads to wettability alterations in the seals. Such wettability alterations allow seals to leak by multiphase Darcy flow, which would hardly happen if the seals were water wet and with sufficiently small pore throats.One implication of this model is that capillary sealing will be effective only for a limited period of time. The model also predicts that residual oil saturation in the shales as a whole remains low, as the suggested flow paths only develop locally and develop narrow leakage pathways.
Olympic Bidding, Multicultural Nationalism, Terror, and the Epistemological Violence of ‘Making Britain Proud’
Authors: Falcous Mark , Silk Michael L. 
Published: December 2010

AbstractThis paper excavates the entanglement of British nationalist identity politics with sport, terrorism, place re‐imagining, mega‐event bidding, and corporate neoliberalism. We focus on London's 2012 olympic bidding and the coalescence of corporate, state, civic, and sporting interests surrounding the national (re)imaginings that characterised the bid. We open with a critical reading of the bid narratives explicating how selective assertions of Britishness were envisioned through the motifs of harmonious multicultural unity, ‘youth’, and passion for sport. We focus on how these narratives offered up ‘idealised’ multicultural citizens and harmonious diversity as a reactionary form of nationalist ‘pride politics’ (Fortier 2005). We subsequently juxtapose these narratives with a critical reading of English press and political discourse in the aftermath of the 7 July 2005 bombings – the day after London was awarded the olympic games. This juxtaposition reveals the tensions and ambiguities between assertions of inclusive civic nationalism – that apparently transcends ethnic difference – and the geo‐politics of the ‘war on terror’ within Britain's post‐imperial self imaginings. Specifically, we tease out the place – and ambiguities – of the 2012 olympics within these imaginings reading the London games as an exemplar of a soft‐core ideological spectacle informing selective nationalist narratives within the context of unfolding neoliberal politics.
Tolerance to the Prophylactic Effects of Carbamazepine and Related Mood Stabilizers in the Treatment of Bipolar Disorders
Authors: Post Robert M. , Weiss Susan R.B. 
Published: December 2010

SUMMARYTolerance development after successful long‐term treatment of bipolar disorder is under recognized, as are ways to prevent or show its occurrence or reverse it once it has occurred. We review the clinical literature which suggests that tolerance can develop to most treatment approaches in bipolar illness and present an animal model of tolerance development to anticonvulsant effects of carbamazepine or lamotrigine on amgydala‐kindled seizures. In this model tolerance does not have a pharmacokinetic basis, but is contingent upon the drug being present in the brain at the time of amygdala stimulation. The occurrence of seizures in the absence of drug is sufficient to reverse tolerance and re‐establish anticonvulsant efficacy. Based on the model, we hypothesize that some episode‐induced compensatory adaptive changes in gene expression fail to occur in tolerant subjects and that episodes off medication re‐induce these changes and renew drug effectiveness. Approaches that slow or reverse tolerance development in the animal model are reviewed so that they can be tested for their applicability in the clinic. Criteria for assessing tolerance development are offered in the hope that this will facilitate a more systemic literature about its prevalence, prevention, and reversal. Careful longitudinal monitoring of episode occurrence is essential to understanding tolerance development in the affective disorder and its treatment.
Metastasis in the subcarinal lymph node with unknown primary tumor
Authors: Eckardt Jens , Olsen Karen Ege , Petersen Henrik 
Published: December 2010

AbstractA 59‐year‐old man with previous anaplastic large cell T‐cell lymphoma stage 3A was admitted with an isolated positron emission tomography(PET)‐positive spot in a subcarinal lymph node. Diagnosis was achieved with endobronchial ultrasound‐guided fine‐needle aspiration demonstrating a well‐differentiated squamous cell carcinoma but no primary tumor was visible on PET‐computed tomography. Because of his previous lymphoma the patient was scheduled for mediastinoscopy where the diagnosis was confirmed. Subsequent gastroscopy was normal and a right‐sided thoracotomy showed no evidence of cancer elsewhere, only an inoperable metastasis in a subcarinal lymph node which infiltrated the trachea, esophagus and aorta. Such isolated squamous cell carcinoma in a subcarinal lymph node without a primary tumor despite invasive work‐up has not been reported before.
Evaluation of a Rapid and Completely Automated Real-Time Reverse Transcriptase PCR Assay for Diagnosis of Enteroviral Meningitis
Authors: Nolte Frederick S. , Rogers Beverly B. , Tang Yi-Wei , Oberste M. Steven , Robinson Christine C. , Kehl K. Sue , Rand Kenneth A. , Rotbart Harley A. , Romero Jose R. , Nyquist Ann-Christine , Persing David H. 
Published: December 2010

ABSTRACT

Nucleic acid amplification tests (NAATs) for enterovirus RNA in cerebrospinal fluid (CSF) have emerged as the new gold standard for diagnosis of enteroviral meningitis, and their use can improve the management and decrease the costs for caring for children with enteroviral meningitis. The Xpert EV assay (Cepheid, Sunnyvale, CA) is a rapid, fully automated real-time PCR test for the detection of enterovirus RNA that was approved by the U.S. Food and Drug Administration for
in vitro
diagnostic use in March 2007. In this multicenter trial we established the clinical performance characteristics of the Xpert EV assay in patients presenting with meningitis symptoms relative to clinical truth. Clinical truth for enteroviral meningitis was defined as clinical evidence of meningitis, the absence of another detectable pathogen in CSF, and detection of enterovirus in CSF either by two reference NAATs or by viral culture. A total of 199 prospectively and 235 retrospectively collected specimens were eligible for inclusion in this study. The overall prevalence of enteroviral meningitis was 26.04%. The Xpert EV assay had a sensitivity of 94.69% (90% confidence interval [CI] = 89.79 to 97.66%), specificity of 100% (90% CI = 99.07 to 100%), positive predictive value of 100%, negative predictive value of 98.17, and an accuracy of 98.62% relative to clinical truth. The Xpert EV assay demonstrated a high degree of accuracy for diagnosis of enteroviral meningitis. The simplicity and on-demand capability of the Xpert EV assay should prove to be a valuable adjunct to the evaluation of suspected meningitis cases.
High Proportion of Wrongly Identified Methicillin-Resistant Staphylococcus aureus Carriers by Use of a Rapid Commercial PCR Assay Due to Presence of Staphylococcal Cassette Chromosome Element Lacking the
mecA
Gene
Authors: Blanc Dominique S. , Basset Patrick , Nahimana-Tessemo Immaculée , Jaton Katia , Greub Gilbert , Zanetti Giorgio 
Published: December 2010

ABSTRACT

During a 9-month period, 217 patients were newly diagnosed as methicillin-resistant
Staphylococcus aureus
(MRSA) carriers by using a commercial rapid PCR-based test (GeneXpert). However, no MRSA was recovered by culturing the second swab in 61 of these patients. Further analyses showed that 28 (12.9%) of the patients harbored
S. aureus
isolates with a staphylococcal cassette chromosome element lacking the
mecA
gene and were thus incorrectly determined to be MRSA carriers.
Wild-Type MIC Distributions and Epidemiological Cutoff Values for Posaconazole and Voriconazole and Candida spp. as Determined by 24-Hour CLSI Broth Microdilution
Authors: Pfaller M. A. , Boyken L. , Hollis R. J. , Kroeger J. , Messer S. A. , Tendolkar S. , Diekema D. J. 
Published: December 2010

ABSTRACT

We tested 16,191 strains of
Candida
against posaconazole and voriconazole, using the CLSI M27-A3 broth microdilution (BMD) method (24-h incubation), in order to define wild-type (WT) populations and epidemiological cutoff values (ECVs). From 2001 to 2009, 8,619 isolates of
Candida albicans
, 2,415 isolates of
C. glabrata
, 2,278 isolates of
C. parapsilosis
, 1,895 isolates of
C. tropicalis
, 508 isolates of
C. krusei
, 205 isolates of
C. lusitaniae
, 177 isolates of
C. guilliermondii
, and 93 isolates of
C. kefyr
were obtained from over 100 centers worldwide. The modal MICs (μg/ml) for posaconazole and voriconazole, respectively, were as follows: for
C. albicans
, 0.016 and 0.007; for
C. glabrata
, 0.5 and 0.06; for
C. parapsilosis
, 0.06 and 0.007; for
C. tropicalis
, 0.03 and 0.015; for
C. krusei
, 0.25 and 0.12; for
C. lusitaniae
, 0.03 and 0.007; for
C. guilliermondii
, 0.12 and 0.03; and for
C. kefyr
, 0.06 and 0.007. The ECVs (μg/ml [% of isolates that had MICs equal to or less than the ECV]) for posaconazole and voriconazole, respectively, were as follows: 0.06 (98.5) and 0.03 (98.9) for
C. albicans
, 2 (96.2) and 0.5 (90.4%) for
C. glabrata
, 0.25 (99.3) and 0.12 (97.9) for
C. parapsilosis
, 0.12 (97.6) and 0.06 (97.2) for
C. tropicalis
, 0.5 (99.8) and 0.5 (99.4) for
C. krusei
, 0.12 (95.6) and 0.03 (96.6) for
C. lusitaniae
, 0.5 (98.9) and 0.25 (98.3) for
C. guilliermondii
, and 0.25 (100.0) and 0.015 (100.0) for
C. kefyr
. In the absence of clinical breakpoints (CBPs) for posaconazole, these WT distributions and ECVs will be useful in surveillance for emergence of reduced susceptibility to posaconazole among
Candida
spp. Whereas a CBP for susceptibility of ≤1 μg/ml has been established for voriconazole and all species of
Candida
, it is notable that ECVs for this agent range from 10- to >100-fold lower than the CBP, depending on the species of
Candida
. The CBP is inadequate in detecting the emergence of voriconazole resistance among most
Candida
species encountered clinically. The CBPs for voriconazole should be reassessed, with consideration for development of species-specific CBPs.
Inhibition of Early Stages of HIV-1 Assembly by INI1/hSNF5 Transdominant Negative Mutant S6
Authors: Cano Jennifer , Kalpana Ganjam V. 
Published: December 2010

ABSTRACT

INI1/hSNF5 is an HIV-1 integrase (IN) binding protein specifically incorporated into virions. A truncated mutant of INI1 (S6, amino acids 183 to 294) harboring the minimal IN binding Rpt1 domain potently inhibits HIV-1 particle production in a transdominant manner. The inhibition requires interaction of S6 with IN within Gag-Pol. While INI1 is a nuclear protein and harbors a masked nuclear export signal (NES), the transdominant negative mutant S6 is cytoplasmic, due to the unmasking of NES. Here, we examined the effects of subcellular localization of S6 on HIV-1 inhibition and further investigated the stages of assembly that are affected. We found that targeting a nuclear localization signal-containing S6 variant [NLS-S6(Rpt1)] to the nucleoplasm (but not to the nucleolus) resulted in complete reversal of inhibition of particle production. Electron microscopy indicated that although no electron-dense particles at any stage of assembly were seen in cells expressing S6, virions were produced in cells expressing the rescue mutant NLS-S6(Rpt1) to wild-type levels. Immunofluorescence analysis revealed that p24 exhibited a diffuse pattern of localization within the cytoplasm in cells expressing S6 in contrast to accumulation along the membrane in controls. Pulse-chase analysis indicated that in S6-expressing cells, although Gag(Pr55
gag
) protein translation was unaffected, processing and release of p24 were defective. Together, these results indicate that expression of S6 in the cytoplasm interferes with trafficking of Gag-Pol/Gag to the membrane and causes a defective processing leading to inhibition of assembly at an early stage prior to particle formation and budding.
Genetics Coupled to Quantitative Intact Proteomics Links Heritable Aphid and Endosymbiont Protein Expression to Circulative Polerovirus Transmission
Authors: Cilia M. , Tamborindeguy C. , Fish T. , Howe K. , Thannhauser T. W. , Gray S. 
Published: December 2010

ABSTRACT

Yellow dwarf viruses in the family
Luteoviridae
, which are the causal agents of yellow dwarf disease in cereal crops, are each transmitted most efficiently by different species of aphids in a circulative manner that requires the virus to interact with a multitude of aphid proteins. Aphid proteins differentially expressed in F2
Schizaphis graminum
genotypes segregating for the ability to transmit
Cereal yellow dwarf virus-RPV
(CYDV-RPV) were identified using two-dimensional difference gel electrophoresis (DIGE) coupled to either matrix-assisted laser desorption ionization-tandem mass spectrometry or online nanoscale liquid chromatography coupled to electrospray tandem mass spectrometry. A total of 50 protein spots, containing aphid proteins and proteins from the aphid's obligate and maternally inherited bacterial endosymbiont,
Buchnera
, were identified as differentially expressed between transmission-competent and refractive aphids. Surprisingly, in virus transmission-competent F2 genotypes, the isoelectric points of the
Buchnera
proteins did not match those in the maternal
Buchnera
proteome as expected, but instead they aligned with the
Buchnera
proteome of the transmission-competent paternal parent. Among the aphid proteins identified, many were involved in energy metabolism, membrane trafficking, lipid signaling, and the cytoskeleton. At least eight aphid proteins were expressed as heritable, isoelectric point isoform pairs, one derived from each parental lineage. In the F2 genotypes, the expression of aphid protein isoforms derived from the competent parental lineage aligned with the virus transmission phenotype with high precision. Thus, these isoforms are candidate biomarkers for CYDV-RPV transmission in
S. graminum
. Our combined genetic and DIGE approach also made it possible to predict where several of the proteins may be expressed in refractive aphids with different barriers to transmission. Twelve proteins were predicted to act in the hindgut of the aphid, while six proteins were predicted to be associated with the accessory salivary glands or hemolymph. Knowledge of the proteins that regulate virus transmission and their predicted locations will aid in understanding the biochemical mechanisms regulating circulative virus transmission in aphids, as well as in identifying new targets to block transmission.
Basic Residues in the Nucleocapsid Domain of Gag Are Critical for Late Events of HIV-1 Budding
Authors: Dussupt Vincent , Sette Paola , Bello Nana F. , Javid Melodi P. , Nagashima Kunio , Bouamr Fadila 
Published: December 2010

ABSTRACT

The p6 region of HIV-1 Gag contains two late (L) domains, PTAP and LYPXnL, that bind the cellular proteins Tsg101 and Alix, respectively. These interactions are thought to recruit members of the host fission machinery (ESCRT) to facilitate HIV-1 release. Here we report a new role for the p6-adjacent nucleocapsid (NC) domain in HIV-1 release. The mutation of basic residues in NC caused a pronounced decrease in virus release from 293T cells, although NC mutant Gag proteins retained the ability to interact with cellular membranes and RNAs. Remarkably, electron microscopy analyses of these mutants revealed arrested budding particles at the plasma membrane, analogous to those seen following the disruption of the PTAP motif. This result indicated that the basic residues in NC are important for virus budding. When analyzed in physiologically more relevant T-cell lines (Jurkat and CEM), NC mutant viruses remained tethered to the plasma membrane or to each other by a membranous stalk, suggesting membrane fission impairment. Remarkably, NC mutant release defects were alleviated by the coexpression of a Gag protein carrying a wild-type (WT) NC domain but devoid of all L domain motifs and by providing alternative access to the ESCRT pathway, through the in
trans
expression of the ubiquitin ligase Nedd4.2s. Since NC mutant Gag proteins retained the interaction with Tsg101, we concluded that NC mutant budding arrests might have resulted from the inability of Gag to recruit or utilize members of the host ESCRT machinery that act downstream of Tsg101. Together, these data support a model in which NC plays a critical role in HIV-1 budding.
Interplay between PKCδ and Sp1 on Histone Deacetylase Inhibitor-Mediated Epstein-Barr Virus Reactivation
Authors: Tsai Pei-Fang , Lin Sue-Jane , Weng Pei-Lun , Tsai Shu-Chun , Lin Jiun-Han , Chou Ya-Ching , Tsai Ching-Hwa 
Published: December 2010

ABSTRACT

Epstein-Barr virus (EBV) undergoes latent and lytic replication cycles, and its reactivation from latency to lytic replication is initiated by expression of the two viral immediate-early transactivators, Zta and Rta.
In vitro
, reactivation of EBV can be induced by anti-immunoglobulin, tetradecanoyl phorbol acetate, and histone deacetylase inhibitor (HDACi). We have discovered that protein kinase C delta (PKCδ) is required specifically for EBV reactivation by HDACi. Overexpression of PKCδ is sufficient to induce the activity of the Zta promoter (Zp) but not of the Rta promoter (Rp). Deletion analysis revealed that the ZID element of Zp is important for PKCδ activation. Moreover, the Sp1 putative sequence on ZID is essential for PKCδ-induced Zp activity, and the physiological binding of Sp1 on ZID has been confirmed. After HDACi treatment, activated PKCδ can phosphorylate Sp1 at serine residues and might result in dissociation of the HDAC2 repressor from ZID. HDACi-mediated HDAC2-Sp1 dissociation can be inhibited by the PKCδ inhibitor, Rotterlin. Furthermore, overexpression of HDAC2 can suppress the HDACi-induced Zp activity. Consequently, we hypothesize that HDACi induces PKCδ activation, causing phosphorylation of Sp1, and that the interplay between PKCδ and Sp1 results in the release of HDAC2 repressor from Zp and initiation of Zta expression.