bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kaposi's Sarcoma-Associated Herpesvirus Viral Interferon Regulatory Factor 4 (vIRF4) Targets Expression of Cellular IRF4 and the Myc Gene To Facilitate Lytic Replication
Authors: Lee Hye-Ra , Doğanay Sultan , Chung Brian , Toth Zsolt , Brulois Kevin , Lee Stacy , Kanketayeva Zhansaya , Feng Pinghui , Ha Taekjip , Jung Jae U. 
Published: December 2013

ABSTRACT

Besides an essential transcriptional factor for B cell development and function, cellular interferon regulatory factor 4 (c-IRF4) directly regulates expression of the c-
Myc
gene, which is not only associated with various B cell lymphomas but also required for herpesvirus latency and pathogenesis. Kaposi's sarcoma-associated herpesvirus (KSHV), the etiological agent of Kaposi's sarcoma and primary effusion lymphoma, has developed a unique mechanism to deregulate host antiviral innate immunity and growth control by incorporating four viral homologs (vIRF1 to -4) of cellular IRFs into its genome. Previous studies have shown that several KSHV latent proteins, including vIRF3, vFLIP, and LANA, target the expression, function, and stability of c-Myc to establish and maintain viral latency. Here we report that the KSHV vIRF4 lytic protein robustly suppresses expression of c-
IRF4
and c-
Myc
, reshaping host gene expression profiles to facilitate viral lytic replication. Genomewide gene expression analysis revealed that KSHV vIRF4 grossly affects host gene expression by upregulating and downregulating 118 genes and 166 genes, respectively, by at least 2-fold. Remarkably, vIRF4 suppressed c-
Myc
expression by 11-fold, which was directed primarily by the deregulation of c-
IRF4
expression. Real-time quantitative PCR (RT-qPCR), single-molecule
in situ
hybridization, and chromatin immunoprecipitation assays showed that vIRF4 not only reduces c-
IRF4
expression but also competes with c-IRF4 for binding to the specific promoter region of the c-
Myc
gene, resulting in drastic suppression of c-
Myc
expression. Consequently, the loss of vIRF4 function in the suppression of c-
IRF4
and c-
Myc
expression ultimately led to a reduction of KSHV lytic replication capacity. These results indicate that the KSHV vIRF4 lytic protein comprehensively targets the expression and function of c-IRF4 to downregulate c-
Myc
expression, generating a favorable environment for viral lytic replication. Finally, this study further reinforces the important role of the c-
Myc
gene in KSHV lytic replication and latency.
Enhanced Fusion and Virion Incorporation for HIV-1 Subtype C Envelope Glycoproteins with Compact V1/V2 Domains
Authors: Cavrois Marielle , Neidleman Jason , Santiago Mario L. , Derdeyn Cynthia A. , Hunter Eric , Greene Warner C. 
Published: December 2013

ABSTRACT
In infected people, the HIV-1 envelope glycoprotein (Env) constantly evolves to escape the immune response while retaining the essential elements needed to mediate viral entry into target cells. The extensive genetic variation of Env is particularly striking in the V1/V2 hypervariable domains. In this study, we investigated the trade-off, in terms of fusion efficiency, for encoding V1/V2 domains of different lengths. We found that natural variations in V1/V2 length exert a profound impact on HIV-1 entry. Variants encoding compact V1/V2 domains mediated fusion with higher efficiencies than related Envs encoding longer V1/V2 domains. By exchanging the V1/V2 domains between Envs of the same infected person or between two persons linked by a transmission event, we further demonstrated that V1/V2 domains critically influence both Env incorporation into viral particles and fusion to primary CD4 T cells and monocyte-derived dendritic cells. Shortening the V1/V2 domains consistently increased Env incorporation and fusion, whereas lengthening the V1/V2 domains decreased Env incorporation and fusion. Given that in a new host transmitted founder viruses are distinguished by compact Envs with fewer glycosylation sites, our study points to fusion and possibly Env incorporation into virions as limiting steps for transmission of HIV-1 to a new host and suggests that the length and/or the N-glycosylation profile of the V1/V2 domain influences these early steps in the HIV life cycle.
The Kaposi's Sarcoma-Associated Herpesvirus (KSHV)-Induced 5-Lipoxygenase-Leukotriene B4 Cascade Plays Key Roles in KSHV Latency, Monocyte Recruitment, and Lipogenesis
Authors: Sharma-Walia Neelam , Chandran Karthic , Patel Kinjan , Veettil Mohanan Valiya , Marginean Alexandru 
Published: December 2013

ABSTRACT

Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically associated with Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL). KS lesions are characterized by endothelial cells with multiple copies of the latent KSHV episomal genome, lytic replication in a low percentage of infiltrating monocytes, and inflammatory cytokines plus growth factors. We demonstrated that KSHV utilizes inflammatory cyclooxygenase 2/prostaglandin E
2
to establish and maintain latency (Sharma-Walia, N., A. G. Paul, V. Bottero, S. Sadagopan, M. V. Veettil, N. Kerur, and B. Chandran, PLoS Pathog 6:e1000777, 2010 [doi:10.1371/journal.ppat.1000777]). Here, we evaluated the role of 5-lipoxygenase (5LO) and its chemotactic metabolite leukotriene B4 (LTB4) in KSHV biology. Abundant staining of 5LO was detected in human KS tissue sections. We observed elevated levels of 5LO and high levels of secretion of LTB4 during primary KSHV infection of endothelial cells and in PEL B cells (BCBL-1 and BC-3 cells). Blocking the 5LO/LTB4 cascade inhibited viral latent ORF73, immunomodulatory K5, viral macrophage inflammatory protein 1 (MIP-1), and viral MIP-2 gene expression, without much effect on lytic switch ORF50, immediate early lytic K8, and viral interferon-regulatory factor 2 gene expression. 5LO inhibition significantly downregulated latent viral Cyclin and latency-associated nuclear antigen 2 levels in PEL cells. 5LO/LTB4 inhibition downregulated TH2-related cytokine secretion, elevated TH1-related cytokine secretion, and reduced human monocyte recruitment, adhesion, and transendothelial migration. 5LO/LTB4 inhibition reduced fatty acid synthase (FASN) promoter activity and its expression. Since FASN, a key enzyme required in lipogenesis, is important in KSHV latency, these findings collectively suggest that 5LO/LTB4 play important roles in KSHV biology and that effective inhibition of the 5LO/LTB4 pathway could potentially be used in treatment to control KS/PEL.
Role of the Nuclease Activities Encoded by Herpes Simplex Virus 1 UL12 in Viral Replication and Neurovirulence
Authors: Fujii Hikaru , Mugitani Michio , Koyanagi Naoto , Liu Zhuoming , Tsuda Shumpei , Arii Jun , Kato Akihisa , Kawaguchi Yasushi 
Published: December 2013

ABSTRACT

Enzyme-dead mutations in the herpes simplex virus 1 UL12 gene that abolished its endo- and exonuclease activities only slightly reduced viral replication in cell cultures. However, the UL12 null mutation significantly reduced viral replication, suggesting that a UL12 function(s) unrelated to its nuclease activities played a major role in viral replication. In contrast, the enzyme-dead mutations significantly reduced viral neurovirulence in mice, suggesting that UL12 nuclease activities were critical for viral pathogenesis
in vivo
.
Thromboprophylaxis only during hospitalisation in fast-track hip and knee arthroplasty, a prospective cohort study
Authors: Jørgensen Christoffer C , Jacobsen Michael K , Soeballe Kjeld , Hansen Torben B , Husted Henrik , Kjærsgaard-Andersen Per , Hansen Lars T , Laursen Mogens B , Kehlet Henrik 
Published: December 2013

ObjectivesInternational guidelines recommend thrombosis prophylaxis after total hip arthroplasty (THA) and total knee arthroplasty (TKA) for up to 35 days. However, previous studies often have hospital stays (length of stay; LOS) of 8–12 days and not considering early mobilisation, which may reduce incidence of venous thromboembolic events (VTE). We investigated the incidence of any symptomatic thromboembolic events (TEEs) with only in-hospital prophylaxis if LOS ≤5 days after fast-track THA and TKA.DesignA prospective descriptive multicentre cohort study in fast-track THA and TKA from February 2010 to December 2011, with complete 90-day follow-up through the Danish National Patient Registry and patient files.Setting6 Danish high-volume centres with a similar standardised fast-track setup, including spinal anaesthesia, opioid-sparing analgesia, early mobilisation, functional discharge criteria and discharge to own home.Participants4924 consecutive unselected unilateral primary THA and TKAs in patients ≥18 years with no preoperative use of continuous ‘potent’ anticoagulative therapy (vitamin K antagonists).ExposureProphylaxis with low-molecular-weight heparin or factor Xa-inhibitors only during hospitalisation when LOS ≤5 days.OutcomesIncidence of symptomatic TEE-related, VTE-related and VTE-related mortality ≤90 days postoperatively.ResultsLOS ≤5 days and thromboprophylaxis only during hospitalisation occurred in 4659 procedures (94.6% of total). Median LOS and prophylaxis duration was 2 days (IQR 2–3) with 0.84% (95% CI 0.62% to 1.15%) TEE and 0.41% (0.26% to 0.64%) VTE during 90-day follow-up. VTE consisted of five pulmonary embolisms (0.11% (0.05% to 0.25%)) and 14 deep venous thrombosis (0.30% (0.18% to 0.50%)). There were four (0.09% (0.04% to 0.23%)) surgery-related deaths, of which 1 (0.02% (0.00% to 0.12%)) was due to pulmonary embolism, and 6 (0.13% (0.06% to 0.28%)) deaths of unknown causes after discharge.ConclusionsThe low incidence of TEE and VTE suggests that in-hospital prophylaxis only, is safe in fast-track THA and TKA patients with LOS of ≤5 days. Guidelines on thromboprophylaxis may need reconsideration in fast-track elective surgery.Trial RegistrationClinicalTrials.gov:NCT01557725
Haemodialysis impairs clopidogrel but not aspirin responsiveness in patients with end-stage renal disease
Authors: Htun Patrik , Kan Tatiana , Mueller Eda , Pohle Cosima , Schindler Ralf , Geisler Tobias , Gawaz Meinrad , Bocksch Wolfgang , Fateh-Moghadam Suzanne 
Published: December 2013

SummaryDual antiplatelet therapy (DAPT) with aspirin (ASA) and clopidogrel (Clp) is the standard treatment to reduce ischaemic coronary events, but in patients with end-stage renal disease (ESRD) the efficacy of Clp remains unclear. Patients with ESRD are at higher risk for coronary artery disease (CAD) and also their post-interventional outcome is worse compared to patients with normal renal function. Little is known about the influence of haemodialysis (HD) on ASA and Clp responsiveness. To assess the effect of HD on ASA- and Clp-responsiveness in patients with documented CAD and ESRD, 31 patients with ESRD (mean age 66.5 ± 1.8 years, 23 male ) on DAPT were evaluated for their ASA and Clp responsiveness with the Verify Now System (Accumetrics Inc.) We measured the antiplatelet effect in all ESRD patients at three time points: T1: just before HD; T2: directly after HD; T3: steady state on a HD free day one week after T1. In our study at baseline 10 (32.3%) patients were ASA-low responder (ASA-LR) and 14 (45.2%) patients Clp-low responder (Clp-LR). There was a significant difference in the PRU values before ( T1) and immediately after HD (T2) [PRU T1=234 (169; 274) vs PRUT2= 247 (199; 278); pT1,2=0.036; ]. Results were shown as median ARU T1 (25th, 75th percentile) or median PRU T1 (25th, 75th percentile). Hence HD seems to impair responsiveness to Clp, resulting in an increase of 6.5 % Clp-LR. No significant differences in the ARU values at the different time-points were found.
A model predicting fluindione dose requirement in elderly inpatients including genotypes, body weight, and amiodarone
Authors: Moreau Caroline , Pautas Eric , Duverlie Charlotte , Berndt Celia , Andro Marion , Mahé Isabelle , Emmerich Joseph , Lacut Karine , Gal Grégoire Le , Peyron Isabelle , Gouin-Thibault Isabelle , Golmard Jean-Louis , Loriot Marie-Anne , Siguret Virginie 
Published: December 2013

SummaryIndandione VKAs have been widely used for decades, especially in Eastern Europe and France. Contrary to coumarin VKAs, the relative contribution of individual factors to the indandione-VKA response is poorly known. In the present multicentre study, we sought to develop and validate a model including genetic and non-genetic factors to predict the daily fluindione dose requirement in elderly patients in whom VKA dosing is challenging. We prospectively recorded clinical and therapeutic data in 230 Caucasian inpatients mean aged 85 ± 6 years, who had reached international normalized ratio stabilisation (range 2.0–3.0) on fluindione. In the derivation cohort (n=156), we analysed 13 polymorphisms in seven genes potentially involved in the pharmacological effect or vitamin-K cycle (VKORC1, CYP4F2, EPHX1) and fluindione metabolism/transport (CYP2C9, CYP2C19, CYP3A5, ABCB1). We built a regression model incorporating non-genetic and genetic data and evaluated the model performances in a separate cohort (n=74). Body-weight, amiodarone intake, VKORC1, CYP4F2, ABCB1 genotypes were retained in the final model, accounting for 31.5% of dose variability. None influence of CYP2C9 was observed. Our final model showed good performances: in 83.3% of the validation cohort patients, the dose was accurately predicted within 5 mg, i.e. the usual step used for adjusting fluindione dosage. In conclusion, in addition to body-weight and amiodarone-intake, pharmacogenetic factors (VKORC1,CYP4F2,ABCB1) related to the pharmacodynamic effect and transport of fluindione significantly influenced the dose requirement in elderly patients while CYP2C9 did not. Studies are required to know whether fluindione could be an alternative VKA in carriers of polymorphic CYP2C9 alleles, hypersensitive to coumarins.
Estudo do preenchimento do sujeito de terceira pessoa em falantes nativos e não-nativos de Português do Brasi
Authors: Gutz Karin 
Published: December 2013

Este trabalho faz um levantamento do preenchimento pronominal do sujeito de terceira pessoa no português brasileiro em narrativas orais e escritas de estudantes do ensino fundamental e médio. Também são comparadas as produções de falantes nativos àquelas de falantes não-nativos (alemães que têm o português como segunda língua). Para a realização deste trabalho 14 alunos (7 nativos e 7 não-nativos) assistiram a um vídeo e narraram a estória do filme oralmente e por escrito. A observação do material mostra que o preenchimento pronominal é a opção mais utilizada nos quatro grupos: não-nativos escrito (100%) > não-nativos oral (83%) > nativos oral (81%) > nativos escrito (59%). Quanto aos falantes não-nativos, o levantamento dos dados foi ao encontro do que se supunha antes da elaboração do trabalho, ou seja, de que o preenchimento pronominal é a opção mais utilizada e, sobretudo, na língua escrita. A obrigatoriedade do preenchimento do sujeito no alemão, língua materna dos informantes, parece estar influenciando sua utilização do português como língua estrangeira. Em relação aos falantes nativos os altos índices de preenchimento na oralidade, bem como os valores significativos verificados na escrita, parecem confirmar a hipótese levantada por Duarte (1993, 2000) de que o português do Brasil estaria alterando o seu sistema linguístico de uma marcação positiva para uma marcação negativa do parâmtero pro-drop. Por fim, foi elaborada uma nova possibilidade de análise, considerando-se que na terceira pessoa, diferentemente da primeira e da segunda, o sujeito nulo não corresponde diretamente ao pronome nulo. Se assim se considerar, estará se ignorando a existência da possibilidade de preenchimento nominal. A reanálise do corpus, considerando portanto o sujeito nulo como a possibilidade de apagamento tanto do pronome como de uma referência nominal, sugere que as verdadeiras porcentagens de sujeitos preenchidos na terceira pessoa são mais semelhantes do que se imaginava àquelas verificadas para a primeira e segunda pessoas. Isso pode ser interpretado como um indício de que a mudança do português do Brasil para uma língua de preenchimento obrigatório do sujeito se encontra em um estágio mais avançado do que se supunha.
Recursos gramaticais para a expressão de proposições dependentes da valência do predicado em Português, Espanhol e Alemão
Authors: Gärtner Eberhard 
Published: December 2013

Neste artigo, depois de esvoçar diferenças metodológicas fundamentais entre a descrição de orações subordinadas nas tradições luso-brasileira e alemã, apresentamos uma descrição de orações completivas e construções equivalentes das três línguas em epígrafe, baseada num modelo gramatical que inclui o significado oracional na descrição gramatical. Consideramos a 'proposição' uma entidade semântica (significado oracional) constituída pelas propriedades semânticas do predicado, por meio da valência semântica do mesmo. A valência sintática, então, decide sobre as construções morfo-sintáticas utilizáveis, com um determinado predicado, para a expressão da respectiva proposição dependente subjacente. Grande parte do artigo é destinada à descrição desses recursos gramaticais de expressão, entre os quais contamos tanto as orações conjuncionais e as construções de infinitivo, nas funções oracionais de sujeito, objeto ou complemento adverbial ou em função completiva nominal, como construções substantivadas, nominalizações e pronominalizações. Discutimos tambem construções com elevação de sujeito, entre as quais incluímos construções conjuncionais, de infinitivo, de gerúndio, gerundiais de infinitivo assim como sintagmas adjetivais, nominais e preposicionais como formas de redução de proposições com predicado nominal e locativo. Finalmente referimo-nos a construções mono-oracionais com elevação de vários argumentos. A comparação com o alemão dá como resultado a maior riqueza das duas línguas ibero-românicas em recursos expressivos para proposições dependentes: a comparação entre estas evidencia sutis diferenças entre o português e o espanhol.
The Nepenthes micramphora (Nepenthaceae) group, with two new species from Mindanao, Philippines
Authors: CHEEK MARTIN , JEBB MATTHEW 
Published: December 2013

The N. micramphora group is erected to accommodate the species N. micramphora, N. abgracilis sp. nov. and N. cid sp. nov. from submontane habitats in Mindanao, Philippines. An overview of the genus in the Philippines is presented in the context of recent discoveries. The greater taxonomic importance of pitcher characters over those of the flowers in the genus is reviewed and hypotheses are provided to account for this phenomenon.
The Impact of Ground-Based Glaciogenic Seeding on Orographic Clouds and Precipitation: A Multisensor Case Study
Authors: Pokharel Binod , Geerts Bart , Jing Xiaoqin 
Published: December 2013

AbstractA case study is presented from the 2012 AgI Seeding Cloud Impact Investigation, an experiment conducted over the Sierra Madre in southern Wyoming to study the impact of ground-based glaciogenic seeding on precipitation. In this case, on 21 February, the temperature in the turbulent boundary layer above cloud base in the target region was just below −8°C, the target orographic clouds contained liquid water, and the storm was rather steady during the measurement period, consisting of an untreated period, followed by a treated period. Eight silver iodide (AgI) generators were used, located on the windward mountain slope. This study is unprecedented in its diversity of radar systems, which included the W-band (3 mm) profiling Wyoming Cloud Radar (WCR), a pair of Ka-band (1 cm) profiling Micro Rain Radars (MRRs), and an X-band (3 cm) scanning Doppler-on-Wheels (DOW) radar. The WCR was on board a research aircraft flying geographically fixed tracks, the DOW was located on the main mountain pass in the target region, one MRR was at this pass, and the other was upstream of the generators. Composite data from the three radars indicate that near-surface reflectivity was higher during seeding, a change that could not be accounted for by storm intensification upstream of the generators. Data from a Parsivel disdrometer at the pass indicate that the concentration of snow crystals of all sizes was larger during seeding, although this change was somewhat delayed. This study highlights the challenge of an observational study to unambiguously identify a seeding signal, as well as the value of cumulative corroborative evidence from independent sources.
Validation of Salinity Data from Surface Drifters
Authors: Reverdin G. , Morisset S. , Boutin J. , Martin N. , Sena-Martins M. , Gaillard F. , Blouch P. , Rolland J. , Font J. , Salvador J. , Fernández P. , Stammer D. 
Published: December 2013

Abstract
Salinity measurements from 119 surface drifters in 2007–12 were assessed; 80% [Surface Velocity Program with a barometer with a salinity sensor (SVP-BS)] and 75% [SVP with salinity (SVP-S)] of the salinity data were found to be usable, after editing out some spikes. Sudden salinity jumps are found in drifter salinity records that are not always associated with temperature jumps, in particular in the wet tropics. A method is proposed to decide whether and how to correct those jumps, and the uncertainty in the correction applied. Northeast of South America, in a region influenced by the Amazon plume and fresh coastal water, drifter salinity is very variable, but a comparison with data from the Soil Moisture and Ocean Salinity satellite suggests that this variability is usually reasonable. The drifter salinity accuracy is then explored based on comparisons with data from Argo floats and from thermosalinographs (TSGs) of ships of opportunity. SVP-S/SVP-BS drifter records do not usually present significant biases within the first 6 months, but afterward biases sometimes need to be corrected (altogether, 16% of the SVP-BS records). Biases start earlier after 3 months for drifters not protected by antifouling paint. For the few drifters for which large corrections were applied to portions of the record, the accuracy cannot be proven to be better than 0.1 psu, and it cannot be proven to be better than 0.5 psu for data in the largest variability area off northeast South America. Elsewhere, after excluding portions of the records with suspicious salinity jumps or when large corrections were applied, the comparisons rule out average biases in individual drifter salinity record larger than 0.02 psu (midlatitudes) and 0.05 psu (tropics).