bluuebunny/crossref_metadata_2025_split huggingface dataset:
Respiratory Syncytial Virus Glycoprotein G Interacts with DC-SIGN and L-SIGN To Activate ERK1 and ERK2
Authors: Johnson Teresa R. , McLellan Jason S. , Graham Barney S. 
Published: November 2011

ABSTRACTRespiratory syncytial virus (RSV) interaction with epithelial and dendritic cells (DCs) is known to require divalent cations, suggesting involvement of C-type lectins. RSV infection and maturation of primary human DCs are reduced in a dose-dependent manner by EDTA. Therefore, we asked whether RSV infection involves DC-SIGN (CD209) or its isoform L-SIGN (CD299) (DC-SIGN/R). Using surface plasmon resonance analysis, we demonstrated that the attachment G glycoprotein of RSV binds both DC- and L-SIGN. However, neutralization of DC- and L-SIGN on primary human DCs did not inhibit RSV infection, demonstrating that interactions between RSV G and DC- or L-SIGN are not required for productive infection. Thus, neither DC- nor L-SIGN represents a functional receptor for RSV. However, inhibition of these interactions increased DC activation, as evidenced by significantly higher levels of alpha interferon (IFN-α), MIP-1α, and MIP-1β in plasmacytoid DCs (pDCs) exposed to RSV after neutralization of DC-and L-SIGN. To understand the molecular interactions involved, intracellular signaling events triggered by purified RSV G glycoprotein were examined in DC- and L-SIGN-transfected 3T3 cells. RSV G interaction with DC- or L-SIGN was shown to stimulate ERK1 and ERK2 phosphorylation, with statistically significant increases relative to mock-infected cells. Neutralization of DC- and L-SIGN reduced ERK1/2 phosphorylation. With increased DC activation following DC- and L-SIGN neutralization and RSV exposure, these data demonstrate that the signaling events mediated by RSV G interactions with DC/L-SIGN are immunomodulatory and diminish DC activation, which may limit induction of RSV-specific immunity.
HLA-B*57 Micropolymorphism Shapes HLA Allele-Specific Epitope Immunogenicity, Selection Pressure, and HIV Immune Control
Authors: Kloverpris Henrik N. , Stryhn Anette , Harndahl Mikkel , van der Stok Mary , Payne Rebecca P. , Matthews Philippa C. , Chen Fabian , Riddell Lynn , Walker Bruce D. , Ndung'u Thumbi , Buus Søren , Goulder Philip 
Published: November 2011

ABSTRACTThe genetic polymorphism that has the greatest impact on immune control of human immunodeficiency virus (HIV) infection is expression of HLA-B*57. Understanding of the mechanism for this strong effect remains incomplete. HLA-B*57 alleles and the closely related HLA-B*5801 are often grouped together because of their similar peptide-binding motifs and HIV disease outcome associations. However, we show here that the apparently small differences between HLA-B*57 alleles, termed HLA-B*57 micropolymorphisms, have a significant impact on immune control of HIV. In a study cohort of >2,000 HIV C-clade-infected subjects from southern Africa, HLA-B*5703 is associated with a lower viral-load set point than HLA-B*5702 and HLA-B*5801 (medians, 5,980, 15,190, and 19,000 HIV copies/ml plasma;P= 0.24 andP= 0.0005). In order to better understand these observed differences in HLA-B*57/5801-mediated immune control of HIV, we undertook, in a study of >1,000 C-clade-infected subjects, a comprehensive analysis of the epitopes presented by these 3 alleles and of the selection pressure imposed on HIV by each response. In contrast to previous studies, we show that each of these three HLA alleles is characterized both by unique CD8+T-cell specificities and by clear-cut differences in selection pressure imposed on the virus by those responses. These studies comprehensively define for the first time the CD8+T-cell responses and immune selection pressures for which these protective alleles are responsible. These findings are consistent with HLA class I alleles mediating effective immune control of HIV through the number of p24 Gag-specific CD8+T-cell responses generated that can drive significant selection pressure on the virus.
Cholesterol-Rich Microdomains as Docking Platforms for Respiratory Syncytial Virus in Normal Human Bronchial Epithelial Cells
Authors: San-Juan-Vergara Homero , Sampayo-Escobar Viviana , Reyes Niradiz , Cha Byeong , Pacheco-Lugo Lisandro , Wong Terianne , Peeples Mark E. , Collins Peter L. , Castaño Maria Eugenia , Mohapatra Shyam S. 
Published: November 2011

ABSTRACT
Respiratory syncytial virus (RSV) is one of the major causes of respiratory infections in children, and it is the main pathogen causing bronchiolitis in infants. The binding and entry mechanism by which RSV infects respiratory epithelial cells has not yet been determined. In this study, the earliest stages of RSV infection in normal human bronchial epithelial cells were probed by tracking virions with fluorescent lipophilic dyes in their membranes. Virions colocalized with cholesterol-containing plasma membrane microdomains, identified by their ability to bind cholera toxin subunit B. Consistent with an important role for cholesterol in RSV infection, cholesterol depletion profoundly inhibited RSV infection, while cholesterol repletion reversed this inhibition. Merger of the outer leaflets of the viral envelope and the cell membrane appeared to be triggered at these sites. Using small-molecule inhibitors, RSV infection was found to be sensitive to Pak1 inhibition, suggesting the requirement of a subsequent step of cytoskeletal reorganization that could involve plasma membrane rearrangements or endocytosis. It appears that RSV entry depends on its ability to dock to cholesterol-rich microdomains (lipid rafts) in the plasma membrane where hemifusion events begin, assisted by a Pak1-dependent process.
Cloning and Analysis of Sooty Mangabey Alternative Coreceptors That Support Simian Immunodeficiency Virus SIVsmm Entry Independently of CCR5
Authors: Elliott Sarah T. C. , Riddick Nadeene E. , Francella Nicholas , Paiardini Mirko , Vanderford Thomas H. , Li Bing , Apetrei Cristian , Sodora Donald L. , Derdeyn Cynthia A. , Silvestri Guido , Collman Ronald G. 
Published: November 2011

ABSTRACT

Natural host sooty mangabeys (SM) infected with simian immunodeficiency virus SIVsmm do not develop AIDS despite high viremia. SM and other natural hosts express very low levels of CCR5 on CD4
+
T cells, and we recently showed that SIVsmm infection and robust replication occur
in vivo
in SM genetically lacking CCR5, indicating the use of additional entry pathways. SIVsmm uses several alternative coreceptors of human origin
in vitro
, but which molecules of SM origin support entry is unknown. We cloned a panel of putative coreceptors from SM and tested their ability to mediate infection, in conjunction with smCD4, by pseudotypes carrying Envs from multiple SIVsmm subtypes. smCXCR6 supported efficient infection by all SIVsmm isolates with entry levels comparable to those for smCCR5, and smGPR15 enabled entry by all isolates at modest levels. smGPR1 and smAPJ supported low and variable entry, whereas smCCR2b, smCCR3, smCCR4, smCCR8, and smCXCR4 were not used by most isolates. In contrast, SIVsmm from rare infected SM with profound CD4
+
T cell loss, previously reported to have expanded use of human coreceptors, including CXCR4, used smCXCR4, smCXCR6, and smCCR5 efficiently and also exhibited robust entry through smCCR3, smCCR8, smGPR1, smGPR15, and smAPJ. Entry was similar with both known alleles of smCD4. These alternative coreceptors, particularly smCXCR6 and smGPR15, may support virus replication in SM that have restricted CCR5 expression as well as SM genetically lacking CCR5. Defining expression of these molecules on SM CD4
+
subsets may delineate distinct natural host target cell populations capable of supporting SIVsmm replication without CD4
+
T cell loss.
Lack of Association between HLA Class II Alleles and
In Vitro
Replication Capacities of Recombinant Viruses Encoding HIV-1 Subtype C Gag-Protease from Chronically Infected Individuals
Authors: Wright Jaclyn K. , Brumme Zabrina L. , Julg Boris , van der Stok Mary , Mncube Zenele , Gao Xiaojiang , Carlson Jonathan M. , Goulder Philip J. R. , Walker Bruce D. , Brockman Mark A. , Ndung'u Thumbi 
Published: November 2011

ABSTRACT

It is unknown whether favorable HLA class II alleles may attenuate HIV-1 through selection pressure in a manner similar to that of protective HLA class I alleles. We investigated the relationship between HLA class II alleles and
in vitro
replication capacities of recombinant viruses encoding HIV-1 subtype C Gag-protease from chronically infected individuals. No associations were found between individual alleles and lower replication capacity, suggesting no significant HIV-1 attenuation by HLA class II-restricted Gag-specific CD4
+
T cell immune pressure.
Aggregates with lysozyme and ovalbumin show features of amyloid-like fibrils
Authors: Sugimoto Yasushi , Kamada Yoshiki , Tokunaga Yuhei , Shinohara Hiroshi , Matsumoto Mitsuharu , Kusakabe Takahiro , Ohkuri Takatoshi , Ueda Tadashi 
Published: November 2011

The interaction of egg-white lysozyme with N-ovalbumin, the native form of egg-white ovalbumin with the denaturation temperature, Tm, of 78 °C, was investigated by the inhibition of lysozyme muramidase activity, differential scanning calorimetry, and circular dichroism assay as indicators. Signals for the interaction were the most prominent when the mixture of lysozyme and N-ovalbumin was co-heated at 72 °C, slightly lower than the Tmof N-ovalbumin. The interaction was also marked when unheated lysozyme was mixed with N-ovalbumin preheated at 72 °C. Moreover, the mixture rapidly formed fibrous precipitates, which were positive for thioflavin T fluorescent emission, a marker for the amyloid fibril formation. Also electron microscopic observation exhibited features of fibrils. The interaction potency of ovalbumin was ascribed to the tryptic fragment ILELPFASGT MSMLVLLPDE VSGLEQLESIINFEK (residues 229–263), derived from the 2B strands 2 and 3 of ovalbumin. From lysozyme, on the other hand, the chymotryptic peptide RNRCKGTDVQAW (residues 112–123), including cluster 6, and the chymotryptic/tryptic peptide GILQINSRW (residues 54–62), including cluster 3, were responsible for the interaction with N-ovalbumin. Interestingly, this nonamer peptide was found to have the ability to self-aggregate. To the authors knowledge, this may be the first report to document the possible involvement of dual proteins in the formation of amyloid-like fibrils.
Wnt-signaling mediates the anti-adipogenic action of lysophosphatidic acid through cross talking with the Rho/Rho associated kinase (ROCK) pathway
Authors: Li L. , Tam L. , Liu L. , Jin T. , Ng D.S. 
Published: November 2011

Lysophosphatidic acid (LPA) is a bioactive phospholipid with a diverse range of biological activities including the modulation of adipogenesis. Treatment of 3T3-L1 cells and 3T3F44A cells with LPA inhibits adipogenesis and reduces expression of PPARγ through activation of RhoGTPase and its downstream Rho associated kinase (ROCK). The mechanism of suppression of PPARγ expression by Rho/ROCK is poorly understood. By treating the differentiating 3T3-L1 cells with various combinations of LPA and ROCK inhibitors, Y-27632 and fasudil, we observed that LPA treatment resulted in attenuation of adipogenesis and a significant reduction in PPARγ mRNA as early as 3 d post-induction. LPA treatment also resulted in significant but delayed upregulation of components of the canonical Wnt signaling, namely Wnt10b mRNA, β-catenin protein, and mRNA expression of β-catenin target genes, detectable at day 7, but not day 3. Treatment of the 3T3-L1 cells with ROCK inhibitors Y-27632 and fasudil revealed a tonic activation of β-catenin/target genes by ROCK. This study identified the existence of a novel cross talk between the Rho/ROCK pathway and the Wnt-signaling pathway. The LPA/Rho/ROCK pathway inhibits expression of PPARγ and adipogenesis in part through a delayed activation of the canonical Wnt-signaling pathway based on increased Wnt10b expression and β-catenin induction.
Constraints on the seismic properties of the middle and lower continental crust
Authors: Lloyd G. E. , Butler R. W. H. , Casey M. , Tatham D. J. , Mainprice D. 
Published: November 2011

Abstract
For the past two decades geodetic measurements have quantified surface displacement fields for the continents, illustrating a general complexity. However, the linkage of geodetically defined displacements in the continents to mantle flow and plate tectonics demands understanding of ductile deformations in the middle and lower continental crust. Advances in seismic anisotropy studies are beginning to allow such work, especially in the Himalaya and Tibet, using passive seismological experiments (e.g. teleseismic receiver functions and records from local earthquakes). Although there is general agreement that measured seismic anisotropy in the middle and lower crust reflects bulk mineral alignment (i.e. crystallographic preferred orientation, CPO), there is a need to calibrate the seismic response to deformation structures and their kinematics. Here, we take on this challenge by deducing the seismic properties of typical mid- and lower-crustal rocks that have experienced ductile deformation through quantitative measures of CPO in samples from appropriate outcrops. The effective database of CPO and hence seismic properties can be expanded by a modelling approach that utilizes ‘rock recipes’ derived from the as-measured individual mineral CPOs combined in varying modal proportions. In addition, different deformation fabrics may be diagnostic of specific deformation kinematics that can serve to constrain interpretations of seismic anisotropy data from the continental crust. Thus, the use of ‘fabric recipes’ based on subsets of individual rock fabric CPO allows the effect of different fabrics (e.g. foliations) to be investigated and interpreted from their seismic response. A key issue is the possible discrimination between continental crustal deformation models with strongly localized simple-shear (ductile fault) fabrics from more distributed (‘pure-shear’) crustal flow. The results of our combined rock and fabric-recipe modelling suggest that the seismic properties of the middle and lower crust depend on deformation state and orientation as well as composition, while reliable interpretation of seismic survey data should incorporate as many seismic properties as possible.
Ed Council and Ed Board
Authors: Owens Barabara Boucher 
Published: November 2011

There are numerous entities within ACM that actively work to support education and outreach. ACM coordinates these myriad efforts through its Education Council and Education Board. As described on their website:
"The Board wields the final executive and decision-making power to facilitate the work of the Education Council.
The Council is a task-force-based, networking-oriented organization whose aim is to promote ACM's educational mission to as wide a range of constituencies as possible: universities, community colleges, high schools, corporations, and the US government."
Text-based description of music for indexing, retrieval, and browsing
Authors: Knees Peter 
Published: November 2011

The aim of this PhD thesis is to develop automatic methods that extract textual descriptions from the Web that can be associated with music pieces. Deriving descriptors for music permits to index large repositories with a diverse set of labels and allows for retrieving pieces and browsing collections. The techniques presented make use of common Web search engines to find related text content on the Web. From this content, descriptors are extracted that may serve as
• labels that facilitate orientation within browsing interfaces to music collections, especially in a three-dimensional browsing interface presented,
• exing terms, used as features in music retrieval systems that can be queried using descriptive free-form text as input, and
• es in adaptive retrieval systems that aim at providing more user-targeted recommendations based on the user's searching behaviour for exploration of music collections.
STAT5A-Mediated SOCS2 Expression Regulates Jak2 and STAT3 Activity Following c-Src Inhibition in Head and Neck Squamous Carcinoma
Authors: Sen Banibrata , Peng Shaohua , Woods Denise M. , Wistuba Ignacio , Bell Diana , El-Naggar Adel K. , Lai Stephen Y. , Johnson Faye M. 
Published: November 2011

AbstractPurpose: The inhibition of c-Src results in a striking reduction in cancer cell invasion, but the effect on cell survival is modest. Defining mechanisms that limit apoptosis following c-Src inhibition could result in an ideal therapeutic approach that both inhibits invasion and leads to apoptosis. In this regard, we discovered a novel feedback loop that results in STAT3 reactivation following sustained c-Src inhibition. Here we define the mechanism underlying this feedback loop and examine the effect of inhibiting it in vivo.Experimental Design: We measured levels and activity of pathway components using PCR, Western blotting, and kinase assays following their manipulation using both molecular and pharmacologic approaches. We used a heterotransplant animal model in which human oral squamous cancer is maintained exclusively in vivo.Results: Following c-Src inhibition, STAT5 is durably inhibited. The inhibition of STAT5A, but not STAT5B, subsequently reduces the expression of suppressors of cytokine signaling 2 (SOCS2). SOCS2 inhibits Janus kinase 2 (Jak2) activity and Jak2–STAT3 binding. SOCS2 expression is necessary for STAT3 inhibition by c-Src inhibitors. Overexpression of SOCS2 is adequate to prevent STAT3 reactivation and to enhance the cytotoxic effects of c-Src inhibition. Likewise, the combination of Jak and c-Src inhibitors led to significantly more apoptosis than either agent alone in vivo.Conclusions: To our knowledge, ours is the first study that fully defines the mechanism underlying this feedback loop, in which sustained c-Src inhibition leads to diminished SOCS2 expression via sustained inhibition of STAT5A, allowing activation of Jak2 and STAT3, Jak2–STAT3 binding, and survival signals. Clin Cancer Res; 18(1); 127–39. ©2011 AACR.
In Silico Screening Reveals Structurally Diverse, Nanomolar Inhibitors of NQO2 That Are Functionally Active in Cells and Can Modulate NF-κB Signaling
Authors: Nolan Karen A. , Dunstan Mark S. , Caraher Mary C. , Scott Katherine A. , Leys David , Stratford Ian J. 
Published: November 2011

Abstract
The National Cancer Institute chemical database has been screened using in silico docking to identify novel nanomolar inhibitors of NRH:quinone oxidoreductase 2 (NQO2). The inhibitors identified from the screen exhibit a diverse range of scaffolds and the structure of one of the inhibitors, NSC13000 cocrystalized with NQO2, has been solved. This has been used to aid the generation of a structure–activity relationship between the computationally derived binding affinity and experimentally measured enzyme inhibitory potency. Many of the compounds are functionally active as inhibitors of NQO2 in cells at nontoxic concentrations. To show this, advantage was taken of the NQO2-mediated toxicity of the chemotherapeutic drug CB1954. The toxicity of this drug is substantially reduced when the function of NQO2 is inhibited, and many of the compounds achieve this in cells at nanomolar concentrations. The NQO2 inhibitors also attenuated TNFα-mediated, NF-кB–driven transcriptional activity. The link between NQO2 and the regulation of NF-кB was confirmed by using short interfering RNA to NQO2 and by the observation that NRH, the cofactor for NQO2 enzyme activity, could regulate NF-кB activity in an NQO2-dependent manner. NF-кB is a potential therapeutic target and this study reveals an underlying mechanism that may be usable for developing new anticancer drugs. Mol Cancer Ther; 11(1); 194–203. ©2011 AACR.
NF-κB in Cancer: A Matter of Life and Death
Authors: Aggarwal Bharat B. , Sung Bokyung 
Published: November 2011

Abstract
Activation of NF-κB has been linked to various cellular processes in cancer, including inflammation, transformation, proliferation, angiogenesis, invasion, metastasis, chemoresistance, and radioresistance. Although acute inflammation mediates innate and humoral immunity, chronic inflammation has been linked to tumorigenesis. Thus, inhibition of NF-κB has therapeutic potential in sensitization of tumors to chemotherapeutic agents; however, generalized suppression of NF-κB can result in serious host toxicity with minimum effect on the tumor. Cancer Discovery; 1(6); 469–71. ©2011 AACR.
Commentary on Enzler et al., p. 496.
Assessment of Valvular Calcification and Inflammation by Positron Emission Tomography in Patients With Aortic Stenosis
Authors: Dweck Marc Richard , Jones Charlotte , Joshi Nikhil V. , Fletcher Alison M. , Richardson Hamish , White Audrey , Marsden Mark , Pessotto Renzo , Clark John C. , Wallace William A. , Salter Donald M. , McKillop Graham , van Beek Edwin J.R. , Boon Nicholas A. , Rudd James H.F. , Newby David E. 
Published: November 2011

Background—
The pathophysiology of aortic stenosis is incompletely understood, and the relative contributions of valvular calcification and inflammation to disease progression are unknown.

Methods and Results—

Patients with aortic sclerosis and mild, moderate, and severe stenosis were compared prospectively with age- and sex-matched control subjects. Aortic valve severity was determined by echocardiography. Calcification and inflammation in the aortic valve were assessed by 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) uptake with the use of positron emission tomography. One hundred twenty-one subjects (20 controls; 20 aortic sclerosis; 25 mild, 33 moderate, and 23 severe aortic stenosis) were administered both 18F-NaF and 18F-FDG. Quantification of tracer uptake within the valve demonstrated excellent interobserver repeatability with no fixed or proportional biases and limits of agreement of ±0.21 (18F-NaF) and ±0.13 (18F-FDG) for maximum tissue-to-background ratios. Activity of both tracers was higher in patients with aortic stenosis than in control subjects (18F-NaF: 2.87±0.82 versus 1.55±0.17; 18F-FDG: 1.58±0.21 versus 1.30±0.13; both
P
<0.001). 18F-NaF uptake displayed a progressive rise with valve severity (
r
2
=0.540,
P
<0.001), with a more modest increase observed for 18F-FDG (
r
2
=0.218,
P
<0.001). Among patients with aortic stenosis, 91% had increased 18F-NaF uptake (>1.97), and 35% had increased 18F-FDG uptake (>1.63). A weak correlation between the activities of these tracers was observed (
r
2
=0.174,
P
<0.001).

Conclusions—
Positron emission tomography is a novel, feasible, and repeatable approach to the evaluation of valvular calcification and inflammation in patients with aortic stenosis. The frequency and magnitude of increased tracer activity correlate with disease severity and are strongest for 18F-NaF.

Clinical Trial Registration—

http://www.clinicaltrials.gov
. Unique identifier: NCT01358513.