bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression of Innate Immune Pathology by Regulatory T Cells during Influenza A Virus Infection of Immunodeficient Mice
Authors: Antunes Inês , Kassiotis George 
Published: October 2010

ABSTRACT
The viral infection of higher vertebrates elicits potent innate and adaptive host immunity. However, an excessive or inappropriate immune response also may lead to host pathology that often is more severe than the direct effects of viral replication. Therefore, several mechanisms exist that regulate the magnitude and class of the immune response. Here, we have examined the potential involvement of regulatory T (Treg) cells in limiting pathology induced by influenza A virus (IAV) infection. Using lymphocyte-deficient mice as hosts, we showed that Treg cell reconstitution resulted in a significant delay in weight loss and prolonged survival following infection. The adoptively transferred Treg cells did not affect the high rate of IAV replication in the lungs of lymphocyte-deficient hosts, and therefore their disease-ameliorating effect was mediated through the suppression of innate immune pathology. Mechanistically, Treg cells reduced the accumulation and altered the distribution of monocytes/macrophages in the lungs of IAV-infected hosts. This reduction in lung monocytosis was associated with a specific delay in monocyte chemotactic protein-2 (MCP-2) induction in the infected lungs. Nevertheless, Treg cells failed to prevent the eventual development of severe disease in lymphocyte-deficient hosts, which likely was caused by the ongoing IAV replication. Indeed, using T-cell-deficient mice, which mounted a T-cell-independent B cell response to IAV, we further showed that the combination of virus-neutralizing antibodies and transferred Treg cells led to the complete prevention of clinical disease following IAV infection. Taken together, these results suggested that innate immune pathology and virus-induced pathology are the two main contributors to pathogenesis during IAV infection.
Cyclin T1/CDK9 Interacts with Influenza A Virus Polymerase and Facilitates Its Association with Cellular RNA Polymerase II
Authors: Zhang Junjie , Li Gang , Ye Xin 
Published: October 2010

ABSTRACT
Influenza virus RNA-dependent RNA polymerase scavenges the 5′ cap from host pre-mRNA to prime viral transcription initiation. It is also well established that viral RNA-dependent RNA polymerase (vRNP) associates with cellular RNA polymerase II (Pol II), on which viral replication depends. Here we report that cyclin T1/CDK9 can interact with influenza virus polymerase and facilitate its association with cellular Pol II. The immunodepletion of cyclin T1/CDK9 totally abolished the association of vRNP with the C-terminal domain (CTD) Ser-2-phosphorylated form of RNA polymerase II. Further studies showed that overexpression of cyclin T1/CDK9 increased the transcription activity of vRNP, while knockdown of cyclin T1/CDK9 impaired viral replication. Our results suggest that cyclin T1/CDK9 serves as an adapter to mediate the interaction of vRNP and RNA Pol II and promote viral transcription.
Common Inbred Strains of the Laboratory Mouse That Are Susceptible to Infection by Mouse Xenotropic Gammaretroviruses and the Human-Derived Retrovirus XMRV
Authors: Baliji Surendranath , Liu Qingping , Kozak Christine A. 
Published: October 2010

ABSTRACTLaboratory mouse strains carry endogenous copies of the xenotropic mouse leukemia viruses (X-MLVs), named for their inability to infect cells of the laboratory mouse. This resistance to exogenous infection is due to a nonpermissive variant of the XPR1 gammaretrovirus receptor, a resistance that also limitsin vivoexpression of germ line X-MLV proviruses capable of producing infectious virus. Because laboratory mice vary widely in their proviral contents and in their virus expression patterns, we screened inbred strains for sequence and functional variants of the XPR1 receptor. We also typed inbred strains and wild mouse species for an endogenous provirus,Bxv1, that is capable of producing infectious X-MLV and that also contributes to the generation of pathogenic recombinant MLVs. We identified the activeBxv1provirus in many common inbred strains and in some JapaneseMus molossinusmice but in none of the other wild mouse species that carry X-MLVs. Our screening forXpr1variants identified the permissiveXpr1sxvallele in 7 strains of laboratory mice, including aBxv1-positive strain, F/St, which is characterized by lifelong X-MLV viremia. Cells from three strains carryingXpr1sxv, namely, SWR, SJL, and SIM.R, were shown to be infectable by X-MLV and XMRV; these strains carry different alleles atFv1and vary in their sensitivities to specific X/P-MLV isolates and XMRV. Several strains withXpr1sxvlack the activeBxv1provirus or other endogenous X-MLVs and may provide a useful model system to evaluate thein vivospread of these gammaretroviruses and their disease potential in their natural host.
The C-Terminal End of Parainfluenza Virus 5 NP Protein Is Important for Virus-Like Particle Production and M-NP Protein Interaction
Authors: Schmitt Phuong Tieu , Ray Greeshma , Schmitt Anthony P. 
Published: October 2010

ABSTRACT

Enveloped virus particles are formed by budding from infected-cell membranes. For paramyxoviruses, viral matrix (M) proteins are key drivers of virus assembly and budding. However, other paramyxovirus proteins, including glycoproteins, nucleocapsid (NP or N) proteins, and C proteins, are also important for particle formation in some cases. To investigate the role of NP protein in parainfluenza virus 5 (PIV5) particle formation, NP protein truncation and substitution mutants were analyzed. Alterations near the C-terminal end of NP protein completely disrupted its virus-like particle (VLP) production function and significantly impaired M-NP protein interaction. Recombinant viruses with altered NP proteins were generated, and these viruses acquired second-site mutations. Recombinant viruses propagated in Vero cells acquired mutations that mainly affected components of the viral polymerase, while recombinant viruses propagated in MDBK cells acquired mutations that mainly affected the viral M protein. Two of the Vero-propagated viruses acquired the same mutation, V/P(S157F), found previously to be responsible for elevated viral gene expression induced by a well-characterized variant of PIV5, P/V-CPI
−
. Vero-propagated viruses caused elevated viral protein synthesis and spread rapidly through infected monolayers by direct cell-cell fusion, bypassing the need to bud infectious virions. Both Vero- and MDBK-propagated viruses exhibited infectivity defects and altered polypeptide composition, consistent with poor incorporation of viral ribonucleoprotein complexes (RNPs) into budding virions. Second-site mutations affecting M protein restored interaction with altered NP proteins in some cases and improved VLP production. These results suggest that multiple avenues are available to paramyxoviruses for overcoming defects in M-NP protein interaction.
International trade versus public health during the FCTC negotiations, 1999-2003
Authors: Mamudu Hadii M , Hammond Ross , Glantz Stanton A 
Published: October 2010

ObjectiveTo examine why the Framework Convention on Tobacco Control did not include an explicit trade provision and delineate the central arguments in the debate over trade provision during the negotiations.MethodsTriangulate interviews with participants in the FCTC negotiations, the FCTC negotiations documents, and tobacco industry documents.ResultsAn explicit FCTC trade provision on relation between international trade and public health became a contentious issue during the negotiations. As a result, two conflicting positions, health-over-trade and opposition to health-over-trade emerged. Opposition to explicit trade language giving health priority was by both tobacco industry and countries that generally supported strong FCTC provisions because of concerns over ‘disguised protectionism’ and setting a precedent whereby governments could forfeit their obligations under pre-existing treaties. Owing to lack of consensus among political actors involved in the negotiations, a compromise position eliminating any mention of trade emerged, which was predicated on belief among some in the public health community that public health would prevail in future trade versus health conflicts.ConclusionThe absence of an explicit FCTC trade provision was due to a political compromise rather than the impact of international trade agreements and decisions on public health and lack of consensus among health advocates. This failure to include an explicit trade provision in the FCTC suggests that the public health community should become more involved in trade and health issues at all levels of governance and press the FCTC Conference of the Parties for clarification of this critical issue.
The role of parents, friends and teachers in adolescents' cigarette smoking and tombak dipping in Sudan
Authors: El-Amin Salma El-Tayeb , Nwaru Bright I , Ginawi Ibrahim , Pisani Paola , Hakama Matti 
Published: October 2010

ObjectiveTo assess the influence of smoking and tombak (local smokeless tobacco) dipping by parents, teachers and friends on cigarette smoking and tombak dipping by school-going Sudanese adolescents.MethodsThis was a school-based cross-sectional survey was conducted in 2005–2006. Logistic regression was used for the analysis. A total of 4277 Sudanese school-going adolescents (aged 11–17 years) from 23 schools who completed an anonymous self-administered questionnaire on the use of tobacco products. Main outcome measures were self-reported tobacco use during the previous month defined current tobacco use. Ever smoking, tombak dipping and other tobacco products were also considered as outcomes.ResultsAfter adjusting for sex, age and school grade, adolescents' smoking habits were strongly associated with the habit in their parents and friends and, more weakly, with tombak dipping by teachers. When adjusted for each other, the association with smoking in friends was unaffected and remained significant (prevalence OR (POR) of having ever smoked was 1.94, 95% CI 1.64 to 2.29; OR of being current smoker was 3.77, 95% CI 2.80 to 5.07). Tobacco smoking in friends was positively associated with adolescents ever tombak dipping (POR 1.81, 95% CI 1.41 to 2.33) and current dipping (OR 3.33, 95% CI 2.20 to 5.05). The association with parental habits was reduced but still significantly elevated. Tombak dipping by teachers was only associated with adolescents ever tobacco smoking.ConclusionsTobacco use by parents, teachers and friends was associated with adolescents' tobacco habits. The influence of friends was the strongest. In developing programmes against adolescents' tobacco habits, there is need to target the influence of these ‘significant others’. Sudan needs to develop and implement comprehensive anti-smoking and anti-tombak dipping legislation to reduce the growing prevalence of such habits.
A convenient route to distannanes, oligostannanes, and polystannanes
Authors: Khan Aman , Gossage Robert A. , Foucher Daniel A. 
Published: October 2010

The quantitative conversion of the tertiary stannane (n-Bu)3SnH (2) into (n-Bu)6Sn2 (4) was achieved by heating the neat hydride material under low pressure or under closed inert atmosphere conditions. A 31% conversion of Ph3SnH (3) to Ph6Sn2 (5) was also observed under low pressure; however, under closed inert atmosphere conditions afforded Ph4Sn (6) as the major product. A mixed distannane, (n-Bu)3SnSnPh3 (7), can also be prepared in good yield utilizing an equal molar ratio of 2 and 3 and the same reaction conditions used to prepare 4. This solvent-free, catalyst-free route to distannanes was extended to a secondary stannane, (n-Bu)2SnH2 (8), which yielded evidence (NMR) for hydride terminated distannane H(n-Bu)2SnSn(n-Bu)2H (9), the polystannane [(n-Bu)2Sn]n (10), and various cyclic stannanes [(n-Bu)2Sn]n=5,6 (11, 12). Further evidence for 10 was afforded by gel permeation chromatography (GPC) where a broad, moderate molecular weight, but highly dispersed polymer, was obtained (Mw = 1.8 × 104 Da, polydispersity index (PDI) = 6.9) and a characteristic UV–vis absorbance (λmax) of ≈370 nm observed.
Phase I Study of NK012, a Novel SN-38–Incorporating Micellar Nanoparticle, in Adult Patients with Solid Tumors
Authors: Hamaguchi Tetsuya , Doi Toshihiko , Eguchi-Nakajima Takako , Kato Ken , Yamada Yasuhide , Shimada Yasuhiro , Fuse Nozomu , Ohtsu Atsushi , Matsumoto Shin-ichi , Takanashi Masaya , Matsumura Yasuhiro 
Published: October 2010

AbstractPurpose: We conducted a first-in-human phase I study to determine the dose-limiting toxicity (DLT), evaluate the pharmacokinetic profile, and document any antitumor activity of NK012, a novel SN-38–incorporating micellar nanoparticle.Experimental Design: Patients with solid tumors refractory to standard therapy, or for which no standard therapy is available, were enrolled. NK012 was administered as a 30-minute infusion every 3 weeks. The starting dose was 2 mg/m2 as SN-38 equivalent, and an accelerated titration schedule was used. Pharmacokinetic analysis was conducted in cycles 1 and 2.Results: Twenty-four patients were enrolled in the study. No UGT1A1*28 homozygous patients were enrolled. Predominant toxicity was neutropenia. Nonhematologic toxicity, especially diarrhea, was mostly grade 1 or 2 during study treatments. Two of nine patients had DLT during cycle 1 at the 28 mg/m2 dose level. DLTs were mostly neutropenia or a related event. Polymer-bound SN-38 (NK012) and SN-38 released from NK012 were slowly eliminated from the plasma, with a terminal-phase half-life of approximately 140 and 210 hours, respectively. Systemic exposure to both polymer-bound SN-38 and SN-38 increased in proportion to the dose. A refractory esophageal cancer patient and a lung carcinoid tumor patient had an objective response and continued the study treatment for 5 and 12 months, respectively.Conclusions: NK012 was well tolerated and showed antitumor activity including partial responses and several occurrences of prolonged stable disease across a variety of advanced refractory cancers. Phase II studies are ongoing. Clin Cancer Res; 16(20); 5058–66. ©2010 AACR.
No Evidence of Sex-Related Survival Disparities among Head and Neck Cancer Patients Receiving Similar Multidisciplinary Care: A Matched-Pair Analysis
Authors: Roberts Jess C. , Li Guojun , Reitzel Lorraine R. , Wei Qingyi , Sturgis Erich M. 
Published: October 2010

Abstract
Purpose: It is unknown whether there are survival disparities between men and women with squamous cell carcinoma of the head and neck (SCCHN), although some data suggest that men have worse outcomes. We conducted a matched-pair study that controlled for several potentially confounding prognostic variables to assess whether a survival advantage exists for female compared with male SCCHN patients receiving similar care.
Experimental Design: We selected 286 female patients and 286 matched male patients from within a prospective epidemiologic study on 1,654 patients with incident SCCHN evaluated and treated at a single large multidisciplinary cancer center. Matching variables included age (±10 y), race/ethnicity, smoking status (never versus ever), tumor site (oral cavity versus oropharynx versus larynx versus hypopharynx), tumor classification (T1-2 versus T3-4), nodal status (negative versus positive), and treatment (surgery, radiation therapy, surgery and radiation therapy, surgery and chemotherapy, chemoradiotherapy, or surgery and chemoradiotherapy).
Results: Matched-pair and log-rank analyses showed no significant differences between women and men in recurrence-free, disease-specific, or overall survival. When the analysis was restricted to individual sites (oral cavity, oropharynx, or larynx/hypopharynx), there was also no evidence of a disparity in survival associated with sex.
Conclusions: We conclude that there is no evidence to suggest that a survival advantage exists for women as compared with men with SCCHN receiving similar multidisciplinary directed care at a tertiary cancer center. Clin Cancer Res; 16(20); 5019–27. ©2010 AACR.
The Insulin-like Growth Factor I Receptor/Insulin Receptor Tyrosine Kinase Inhibitor PQIP Exhibits Enhanced Antitumor Effects in Combination with Chemotherapy Against Colorectal Cancer Models
Authors: Flanigan Sara A. , Pitts Todd M. , Eckhardt S. Gail , Tentler John J. , Tan Aik Choon , Thorburn Andrew , Leong Stephen 
Published: October 2010

Abstract
Purpose: There is growing evidence implicating the importance of the insulin-like growth factor (IGF) pathway in colorectal cancer based upon the results of population studies and preclinical experiments. However, the combination of an IGF-I receptor (IGF-IR) inhibitor with standard colorectal cancer chemotherapies has not yet been evaluated. In this study, we investigated the interaction between PQIP, the dual IGF-IR/insulin receptor tyrosine kinase inhibitor, and standard chemotherapies in colorectal cancer cell line models.
Experimental Design: The antiproliferative effects of PQIP, as a single agent and in combination with 5-fluorouracil, oxaliplatin, or SN38, were analyzed against four colorectal cancer cell lines. Downstream effector proteins, apoptosis, and cell cycle were also assessed in the combination of PQIP and SN-38. Lastly, the efficacy of OSI-906 (a derivative of PQIP) combined with irinotecan was further tested using a human colorectal cancer xenograft model.
Results: Treatment with the combination of PQIP and each of three chemotherapies resulted in an enhanced decrease in proliferation of all four colorectal cancer cell lines compared with single-agent treatment. This inhibition was not associated with a significant induction of apoptosis, but was accompanied by cell cycle arrest and changes in phosphorylation of Akt. Interestingly, antitumor activity between PQIP and SN-38 in vitro was also reflected in the human colorectal cancer xenograft model.
Conclusions: Combination treatment with PQIP, the dual IGF-IR/insulin receptor tyrosine kinase inhibitor, and standard colorectal cancer chemotherapy resulted in enhanced antiproliferative effects against colorectal cancer cell line models, providing a scientific rationale for the testing of OSI-906 and standard colorectal cancer treatment regimens. Clin Cancer Res; 16(22); 5436–46. ©2010 AACR.
A Flexible, Corpus-Driven Model of Regular and Inverse Selectional Preferences
Authors: Erk Katrin , Padó Sebastian , Padó Ulrike 
Published: October 2010

We present a vector space–based model for selectional preferences that predicts plausibility scores for argument headwords. It does not require any lexical resources (such as WordNet). It can be trained either on one corpus with syntactic annotation, or on a combination of a small semantically annotated primary corpus and a large, syntactically analyzed generalization corpus. Our model is able to predict inverse selectional preferences, that is, plausibility scores for predicates given argument heads. We evaluate our model on one NLP task (pseudo-disambiguation) and one cognitive task (prediction of human plausibility judgments), gauging the influence of different parameters and comparing our model against other model classes. We obtain consistent benefits from using the disambiguation and semantic role information provided by a semantically tagged primary corpus. As for parameters, we identify settings that yield good performance across a range of experimental conditions. However, frequency remains a major influence of prediction quality, and we also identify more robust parameter settings suitable for applications with many infrequent items.
Dissociable Neural Systems Supporting Knowledge about Human Character and Appearance in Ourselves and Others
Authors: Moran Joseph M. , Lee Su Mei , Gabrieli John D. E. 
Published: October 2010

Abstract
Functional neuroimaging has identified a neural system comprising posterior cingulate (pCC) and medial prefrontal (mPFC) cortices that appears to mediate self-referential thought. It is unclear whether the two components of this system mediate similar or different psychological processes, and how specific this system is for self relative to others. In an fMRI study, we compared brain responses for evaluation of character (e.g., honest) versus appearance (e.g., svelte) for oneself, one's mother (a close other), and President Bush (a distant other). There was a double dissociation between dorsal mPFC, which was more engaged for character than appearance judgments, and pCC, which was more engaged for appearance than character judgments. A ventral region of mPFC was engaged for judgments involving one's own character and appearance, and one's mother's character, but not her appearance. A follow-up behavioral study indicated that participants rate their own character and appearance, and their mother's character, but not her appearance, as important in their self-concept. This suggests that ventral mPFC activation reflects its role in processing information relevant to the self, but not limited to the self. Thus, specific neural systems mediate specific aspects of thinking about character and appearance in oneself and in others.
Effects of Emotional Preferences on Value-based Decision-making Are Mediated by Mentalizing and Not Reward Networks
Authors: Evans Simon , Fleming Stephen M. , Dolan Raymond J. , Averbeck Bruno B. 
Published: October 2010

Abstract
Real-world decision-making often involves social considerations. Consequently, the social value of stimuli can induce preferences in choice behavior. However, it is unknown how financial and social values are integrated in the brain. Here, we investigated how smiling and angry face stimuli interacted with financial reward feedback in a stochastically rewarded decision-making task. Subjects reliably preferred the smiling faces despite equivalent reward feedback, demonstrating a socially driven bias. We fit a Bayesian reinforcement learning model to factor the effects of financial rewards and emotion preferences in individual subjects, and regressed model predictions on the trial-by-trial fMRI signal. Activity in the subcallosal cingulate and the ventral striatum, both involved in reward learning, correlated with financial reward feedback, whereas the differential contribution of social value activated dorsal temporo-parietal junction and dorsal anterior cingulate cortex, previously proposed as components of a mentalizing network. We conclude that the impact of social stimuli on value-based decision processes is mediated by effects in brain regions partially separable from classical reward circuitry.
The Corollary Discharge in Humans Is Related to Synchronous Neural Oscillations
Authors: Chen Chi-Ming A. , Mathalon Daniel H. , Roach Brian J. , Cavus Idil , Spencer Dennis D. , Ford Judith M. 
Published: October 2010

Abstract
How do animals distinguish between sensations coming from external sources and those resulting from their own actions? A corollary discharge system has evolved that involves the transmission of a copy of motor commands to sensory cortex, where the expected sensation is generated. Through this mechanism, sensations are tagged as coming from self, and responsiveness to them is minimized. The present study investigated whether neural phase synchrony between motor command and auditory cortical areas is related to the suppression of the auditory cortical response. We recorded electrocorticograms from the human brain during a vocalizing/listening task. Neural phase synchrony between Broca's area and auditory cortex in the gamma band (35 to ∼50 Hz) in the 50-msec time window preceding speech onset was greater during vocalizing than during listening to a playback of the same spoken sounds. Because prespeech neural synchrony was correlated (r = −.83, p = .006), with the subsequent suppression of the auditory cortical response to the spoken sound, we hypothesize that phase synchrony in the gamma band between Broca's area and auditory cortex is the neural instantiation of the transmission of a copy of motor commands. We suggest that neural phase synchrony of gamma frequencies may contribute to transmission of corollary discharges in humans.