bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Detection and Discrimination of Campylobacter Species by Use of Confocal Micro-Raman Spectroscopy and Multilocus Sequence Typing
Authors: Lu Xiaonan , Huang Qian , Miller William G. , Aston D. Eric , Xu Jie , Xue Feng , Zhang Hongwei , Rasco Barbara A. , Wang Shuo , Konkel Michael E. 
Published: June 2012

ABSTRACT

A novel strategy for the rapid detection and identification of traditional and emerging
Campylobacter
strains based upon Raman spectroscopy (532 nm) is presented here. A total of 200 reference strains and clinical isolates of 11 different
Campylobacter
species recovered from infected animals and humans from China and North America were used to establish a global Raman spectroscopy-based dendrogram model for
Campylobacter
identification to the species level and cross validated for its feasibility to predict
Campylobacter
-associated food-borne outbreaks. Bayesian probability coupled with Monte Carlo estimation was employed to validate the established Raman classification model on the basis of the selected principal components, mainly protein secondary structures, on the
Campylobacter
cell membrane. This Raman spectroscopy-based typing technique correlates well with multilocus sequence typing and has an average recognition rate of 97.21%. Discriminatory power for the Raman classification model had a Simpson index of diversity of 0.968. Intra- and interlaboratory reproducibility with different instrumentation yielded differentiation index values of 4.79 to 6.03 for wave numbers between 1,800 and 650 cm
−1
and demonstrated the feasibility of using this spectroscopic method at different laboratories. Our Raman spectroscopy-based partial least-squares regression model could precisely discriminate and quantify the actual concentration of a specific
Campylobacter
strain in a bacterial mixture (regression coefficient, >0.98; residual prediction deviation, >7.88). A standard protocol for sample preparation, spectral collection, model validation, and data analyses was established for the Raman spectroscopic technique. Raman spectroscopy may have advantages over traditional genotyping methods for bacterial epidemiology, such as detection speed and accuracy of identification to the species level.
HTLV-1 Tax-Induced Rapid Senescence Is Driven by the Transcriptional Activity of NF-κB and Depends on Chronically Activated IKKα and p65/RelA
Authors: Ho Yik-Khuan , Zhi Huijun , DeBiaso Dominic , Philip Subha , Shih Hsiu-Ming , Giam Chou-Zen 
Published: June 2012

ABSTRACT

The HTLV-1 oncoprotein Tax is a potent activator of classical and alternative NF-κB pathways and is thought to promote cell proliferation and transformation via NF-κB activation. We showed recently that hyperactivation of NF-κB by Tax triggers a cellular senescence response (H. Zhi et al., PLoS Pathog. 7:e1002025, 2011). Inhibition of NF-κB activation by expression of I-κBα superrepressor or by small hairpin RNA (shRNA)-mediated knockdown of p65/RelA rescues cells from Tax-induced rapid senescence (Tax-IRS). Here we demonstrate that Tax-IRS is driven by the transcriptional activity of NF-κB. Knockdown of IKKγ, the primary Tax target, by shRNAs abrogated Tax-mediated activation of both classical and alternative NF-κB pathways and rendered knockdown cells resistant to Tax-IRS. Consistent with a critical role of IKKα in the transcriptional activity of NF-κB, IKKα deficiency drastically decreased NF-κB
trans
-activation by Tax, although it only modestly reduced Tax-mediated I-κBα degradation and NF-κB nuclear localization. In contrast, although IKKβ knockdown attenuated Tax-induced NF-κB transcriptional activation, the residual NF-κB activation in IKKβ-deficient cells was sufficient to trigger Tax-IRS. Importantly, the phenotypes of NIK and TAK1 knockdown were similar to those of IKKα and IKKβ knockdown, respectively. Finally, double knockdown of RelB and p100 had a minor effect on senescence induction by Tax. These data suggest that Tax, through its interaction with IKKγ, helps recruit NIK and TAK1 for IKKα and IKKβ activation, respectively. In the presence of Tax, the delineation between the classical and alternative NF-κB pathways becomes obscured. The senescence checkpoint triggered by Tax is driven by the transcriptional activity of NF-κB, which depends on activated IKKα and p65/RelA.
Structural Basis of Ligand Interactions of the Large Extracellular Domain of Tetraspanin CD81
Authors: Rajesh Sundaresan , Sridhar Pooja , Tews Birke Andrea , Fénéant Lucie , Cocquerel Laurence , Ward Douglas G. , Berditchevski Fedor , Overduin Michael 
Published: June 2012

ABSTRACTHepatitis C virus (HCV) causes chronic liver disease, cirrhosis, and primary liver cancer. Despite 130 million people being at risk worldwide, no vaccine exists, and effective therapy is limited by drug resistance, toxicity, and high costs. The tetraspanin CD81 is an essential entry-level receptor required for HCV infection of hepatocytes and represents a critical target for intervention. In this study, we report the first structural characterization of the large extracellular loop of CD81, expressed in mammalian cells and studied in physiological solutions. The HCV E2 glycoprotein recognizes CD81 through a dynamic loop on the helical bundle, which was shown by nuclear magnetic resonance (NMR) spectroscopy to adopt a conformation distinct from that seen in crystals. A novel membrane binding interface was revealed adjacent to the exposed HCV interaction site in the extracellular loop of CD81. The binding pockets for two proposed inhibitors of the CD81-HCV interaction, namely, benzyl salicylate and fexofenadine, were shown to overlap the HCV and membrane interaction sites. Although the dynamic loop region targeted by these compounds presents challenges for structure-based design, the NMR assignments enable realistic screening and validation of ligands. Together, these data provide an improved avenue for developing potent agents that specifically block CD81-HCV interaction and also pave a way for elucidating the recognition mechanisms of diverse tetraspanins.
Neutralizing Antibody Escape during HIV-1 Mother-to-Child Transmission Involves Conformational Masking of Distal Epitopes in Envelope
Authors: Goo Leslie , Milligan Caitlin , Simonich Cassandra A. , Nduati Ruth , Overbaugh Julie 
Published: June 2012

ABSTRACT
HIV-1 variants transmitted to infants are often resistant to maternal neutralizing antibodies (NAbs), suggesting that they have escaped maternal NAb pressure. To define the molecular basis of NAb escape that contributes to selection of transmitted variants, we analyzed 5 viruses from 2 mother-to-child transmission pairs, in which the infant virus, but not the maternal virus, was resistant to neutralization by maternal plasma near transmission. We generated chimeric viruses between maternal and infant envelope clones obtained near transmission and examined neutralization by maternal plasma. The molecular determinants of NAb escape were distinct, even when comparing two maternal variants to the transmitted infant virus within one pair, in which insertions in V4 of gp120 and substitutions in HR2 of gp41 conferred neutralization resistance. In another pair, deletions and substitutions in V1 to V3 conferred resistance, but neither V1/V2 nor V3 alone was sufficient. Although the sequence determinants of escape were distinct, all of them involved modifications of potential N-linked glycosylation sites. None of the regions that mediated escape were major linear targets of maternal NAbs because corresponding peptides failed to compete for neutralization. Instead, these regions disrupted multiple distal epitopes targeted by HIV-1-specific monoclonal antibodies, suggesting that escape from maternal NAbs occurred through conformational masking of distal epitopes. This strategy likely allows HIV-1 to utilize relatively limited changes in the envelope to preserve the ability to infect a new host while simultaneously evading multiple NAb specificities present in maternal plasma.
A Common Strategy for Host RNA Degradation by Divergent Viruses
Authors: Gaglia Marta Maria , Covarrubias Sergio , Wong Wesley , Glaunsinger Britt A. 
Published: June 2012

ABSTRACT
Infection with gammaherpesviruses, alphaherpesviruses, and betacoronaviruses can result in widespread mRNA degradation, in each case initiated predominantly by a single viral factor. Although not homologous, these factors exhibit significant mechanistic similarities. In cells, each targets translatable RNAs for cleavage and requires host Xrn1 to complete RNA degradation, although the mechanism of targeting and the position of the primary cleavage differ. Thus, multiple host shutoff factors have converged upon a common mRNA degradation pathway.
Conservation of a Unique Mechanism of Immune Evasion across the Lyssavirus Genus
Authors: Wiltzer L. , Larrous F. , Oksayan S. , Ito N. , Marsh G. A. , Wang L. F. , Blondel D. , Bourhy H. , Jans D. A. , Moseley G. W. 
Published: June 2012

ABSTRACT

The evasion of host innate immunity by
Rabies virus
, the prototype of the genus
Lyssavirus
, depends on a unique mechanism of selective targeting of interferon-activated STAT proteins by the viral phosphoprotein (P-protein). However, the immune evasion strategies of other lyssaviruses, including several lethal human pathogens, are unresolved. Here, we show that this mechanism is conserved between the most distantly related members of the genus, providing important insights into the pathogenesis and potential therapeutic targeting of lyssaviruses.
EMBEDDING ℤ2 * Z AS A DISCRETE SUBGROUP INTO SMALL LINEAR GROUPS
Authors: SOIFER G. A. 
Published: June 2012

At the 2011 Durham Conference "Geometry and Arithmetic of Lattices" M. Kapovich formulated the following Question. Does there exist an embedding ℤ2 * ℤ ↪ SL(3, ℤ)? The goal of the paper is to prove the following Main Theorem.If p and m are arbitrary positive integers then there exists an embeddingℤ2 * Fm ↪ SL(3, ℤ[1/p]).
Targeting eNOS in Pancreatic Cancer
Authors: Lampson Benjamin L. , Kendall S. DiSean , Ancrile Brooke B. , Morrison Meghan M. , Shealy Michael J. , Barrientos Katharine S. , Crowe Matthew S. , Kashatus David F. , White Rebekah R. , Gurley Susan B. , Cardona Diana M. , Counter Christopher M. 
Published: June 2012

Abstract
Mortality from pancreatic ductal adenocarcinoma cancer (PDAC) is among the highest of any cancer and frontline therapy has changed little in years. Activation of endothelial nitric oxide synthase (eNOS, NOS3, or NOS III) has been implicated recently in the pathogenesis of PDACs. In this study, we used genetically engineered mouse and human xenograft models to evaluate the consequences of targeting eNOS in PDACs. Genetic deficiency in eNOS limited the development of preinvasive pancreatic lesions and trended toward an extended lifespan in mice with advanced pancreatic cancer. These effects were also observed upon oral administration of the clinically evaluated NOS small molecule inhibitor NG-nitro-L-arginine methyl ester (l-NAME). Similarly, other transgenic models of oncogenic KRas–driven tumors responded to l-NAME treatment. Finally, these results were recapitulated in xenograft models of human pancreatic cancer, in which l-NAME was found to broadly inhibit tumorigenic growth. Taken together, our findings offer preclinical proof-of-principle to repurpose l-NAME for clinical investigations in treatment of PDACs and possibly other KRas-driven human cancers. Cancer Res; 72(17); 4472–82. ©2012 AACR.
Unraveling the “Known Unknowns”: Lessons and Reflections from the New Directions in Leukemia Research 2012 Conference
Authors: White Deborah L. , Brown Anna L. , D'Andrea Richard J. , Rice Alison M. 
Published: June 2012

Abstract
Patients diagnosed with leukemia approach their treatment with the hope of cure despite the effect on their quality of life. Some patients will be cured, others will die from treatment, and some will die of their disease. A common theme at the New Directions in Leukemia Research (NDLR 2012) meeting was that cure will come if the drivers of the disease are better understood. Key messages included the power of combination platforms to understand the genetic and epigenetic modifications in leukemia to enable development of rational therapies, which can be tested via new clinical trial designs ensuring rapid clinical implementation. Cancer Res; 72(17); 4300–3. ©2012 AACR.
Venous thromboembolism: Annualised United States models for total, hospital-acquired and preventable costs utilising long-term attack rates
Authors: Borrego Matthew E. , Woersching Alex L. , Federici Robert , Downey Ross , Tiongson Jay , Bieniarz Mark C. , Cavanaugh Brendan J. , Spyropoulos Alex C. , Mahan Charles E. 
Published: June 2012

SummaryHealthcare reform is upon the United States (US) healthcare system. Prioritisation of preventative efforts will guide necessary transitions within the US healthcare system. While annual deep-vein thrombosis (DVT) costs have recently been defined at the US national level, annual pulmonary embolism (PE) and venous thromboembolism (VTE) costs have not yet been defined. A decision tree and cost model were developed to estimate US health care costs for total PE, total hospital-acquired PE, and total hospital-acquired “preventable” PE. The previously published DVT cost model was modified, updated and combined with the PE cost model to elucidate the same three categories of costs for VTE. Direct and indirect costs were also delineated. For VTE in the base model, annual cost ranges in 2011 US dollars for total, hospital-acquired, and hospital-acquired “preventable” costs and were $13.5-$27.2, $9.0-$18.2, and $4.5-$14.2 billion, respectively. The first sensitivity analysis, with higher incidence rates and costs, demonstrated annual US total, hospital-acquired, and hospital-acquired “preventable” VTE costs ranging from $32.1-$69.3, $23.7-$51.5, and $11.9-$39.3 billion, respectively. The second sensitivity analysis with long-term attack rates (LTAR) for recurrent events and post-thrombotic syndrome and chronic pulmonary thromboembolic hypertension demonstrated annual US total, hospital-acquired, and hospital-acquired “preventable” VTE costs ranging from $15.4-$34.4, $10.3-$25.4, and $5.1-$19.1 billion, respectively. PE costs comprised a majority of the VTE costs. Prioritisation of effective VTE preventative strategies will reduce significant costs, morbidity and mortality within the US healthcare system. The cost models may be utilised to estimate other countries’ costs or VTE-specific disease states.
Fractalkine – a local inflammatory marker aggravating platelet activation at the vulnerable plaque
Authors: Flierl Ulrike , Schäfer Andreas 
Published: June 2012

SummaryChemokines play an important role in inducing chemotaxis of cells, piloting white blood cells in immune surveillance and are crucial parts in the development and progression of atherosclerosis. Platelets are mandatory players in the initiation of atherosclerotic lesion formation and are susceptible targets for and producers of chemokines. Several chemokine receptors on platelets have been described previously, amongst them CX3CR1, the receptor for fractalkine. The unique chemokine fractalkine (CX3CL1, FKN) exists as a soluble as well as a membrane-anchored glycoprotein. Its essential role in the formation of atherosclerotic lesions and atherosclerosis progression has been impressively described in mouse models. Moreover, fractalkine induces platelet activation and adhesion via a functional fractalkine receptor (CX3CR1) expressed on the platelet surface. Platelet activation via the FKN/CX3CR1-axis triggers leukocyte adhesion to activated endothelium, and fractalkine-induced platelet P-selectin is mandatory for leukocyte recruitment under arterial flow conditions. This review summarises the role of fractalkine as a potential local inflammatory mediator which influences platelet activation in the setting of atherosclerosis. Beyond that, aspects of a potential interaction between fractalkine and platelet responsiveness to antiplatelet drugs are described. Furthermore, the possible impact of high-density lipoprotein cholesterol (HDL-C) on atherosclerosis progression, platelet activation and fractalkine signalling are discussed.
Aberrant Neurogenesis After Stroke
Authors: Niv Fanny , Keiner Silke , Krishna -K , Witte Otto W. , Lie Dieter Chichung , Redecker Christoph 
Published: June 2012

Background and Purpose—
Adult neurogenesis in the dentate gyrus is a unique form of brain plasticity that is strongly stimulated after stroke. We investigate the morphological properties of new granule cells, which are born and develop after the ischemic insult, and query whether these adult-born neurons properly integrate into the pre-existing hippocampal circuitries.

Methods—
Two well-established models were used to induce either small cortical infarcts (photothrombosis model) or large territorial infarcts (transient middle cerebral artery occlusion model). New granule cells were labeled 4 days after the initial insult by intrahippocampal injection of a retroviral vector encoding green fluorescent protein and newborn neurons were morphologically analyzed using a semiautomatic Neurolucida system and confocal laser scanning microscopy at 6 weeks.

Results—
Approximately 5% to 10% of newborn granule cells displayed significant morphological abnormalities comprising additional basal dendrites and, after middle cerebral artery occlusion, also ectopic cell position. The extent of morphological abnormalities was higher after large territorial infarcts and seems to depend on the severity of ischemic damage. An increased portion of mushroom spines in aberrant neurons suggests stable synaptic integration. However, poststroke generated granule cells with regular appearance also demonstrate alterations in dendritic complexity and spine morphology.

Conclusions—
The remarkable stimulation of dentate neurogenesis after stroke coincides with an increased rate of aberrantly integrated neurons, which may contribute to functional impairments and, hypothetically, favor pathogenesis of adjustment disorders, cognitive deficits, or epilepsy often seen in stroke patients.
Intracellular cyclophilin A is an important Ca2+ regulator in platelets and critically involved in arterial thrombus formation
Authors: Elvers Margitta , Herrmann Annika , Seizer Peter , Münzer Patrick , Beck Sandra , Schönberger Tanja , Borst Oliver , Martin-Romero Francisco Javier , Lang Florian , May Andreas E. , Gawaz Meinrad 
Published: June 2012

Abstract
Platelet adhesion and aggregation play a critical role in primary hemostasis. Uncontrolled platelet activation leads to pathologic thrombus formation and organ failure. The decisive central step for different processes of platelet activation is the increase in cytosolic Ca2+ activity ([Ca2+]i). Activation-dependent depletion of intracellular Ca2+ stores triggers Ca2+ entry from the extracellular space. Stromal interaction molecule 1 (STIM1) has been identified as a Ca2+ sensor that regulates store-operated Ca2+ entry through activation of the pore-forming subunit Orai1, the major store-operated Ca2+ entry channel in platelets. In the present study, we show for the first time that the chaperone protein cyclophilin A (CyPA) acts as a Ca2+ modulator in platelets. CyPA deficiency strongly blunted activation-induced Ca2+ mobilization from intracellular stores and Ca2+ influx from the extracellular compartment and thus impaired platelet activation substantially. Furthermore, the phosphorylation of the Ca2+ sensor STIM1 was abrogated upon CyPA deficiency, as shown by immunoprecipitation studies. In a mouse model of arterial thrombosis, CyPA-deficient mice were protected against arterial thrombosis, whereas bleeding time was not affected. The results of the present study identified CyPA as an important Ca2+ regulator in platelets, a critical mechanism for arterial thrombosis.
Identifying promoter features of co-regulated genes with similar network motifs
Authors: Harari Oscar , del Val Coral , Romero-Zaliz Rocío , Shin Dongwoo , Huang Henry , Groisman Eduardo A , Zwir Igor 
Published: June 2012

Abstract

Background
A large amount of computational and experimental work has been devoted to uncovering network motifs in gene regulatory networks. The leading hypothesis is that evolutionary processes independently selected recurrent architectural relationships among regulators and target genes (motifs) to produce characteristic expression patterns of its members. However, even with the same architecture, the genes may still be differentially expressed. Therefore, to define fully the expression of a group of genes, the strength of the connections in a network motif must be specified, and the cis-promoter features that participate in the regulation must be determined.

Results
We have developed a model-based approach to analyze proteobacterial genomes for promoter features that is specifically designed to account for the variability in sequence, location and topology intrinsic to differential gene expression. We provide methods for annotating regulatory regions by detecting their subjacent cis-features. This includes identifying binding sites for a transcriptional regulator, distinguishing between activation and repression sites, direct and reverse orientation, and among sequences that weakly reflect a particular pattern; binding sites for the RNA polymerase, characterizing different classes, and locations relative to the transcription factor binding sites; the presence of riboswitches in the 5'UTR, and for other transcription factors. We applied our approach to characterize network motifs controlled by the PhoP/PhoQ regulatory system of Escherichia coli and Salmonella enterica serovar Typhimurium. We identified key features that enable the PhoP protein to control its target genes, and distinct features may produce different expression patterns even within the same network motif.

Conclusion
Global transcriptional regulators control multiple promoters by a variety of network motifs. This is clearly the case for the regulatory protein PhoP. In this work, we studied this regulatory protein and demonstrated that understanding gene expression does not only require identifying a set of connexions or network motif, but also the cis-acting elements participating in each of these connexions.