bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leishmania amazonensis Amastigotes Trigger Neutrophil Activation but Resist Neutrophil Microbicidal Mechanisms
Authors: Carlsen Eric D. , Hay Christie , Henard Calvin A. , Popov Vsevolod , Garg Nisha Jain , Soong Lynn 
Published: August 2013

ABSTRACT

Neutrophils are the first cells to infiltrate to the site of
Leishmania
promastigote infection, and these cells help to reduce parasite burden shortly after infection is initiated. Several clinical reports indicate that neutrophil recruitment is sustained over the course of leishmaniasis, and amastigote-laden neutrophils have been isolated from chronically infected patients and experimentally infected animals. The goal of this study was to compare how thioglycolate-elicited murine neutrophils respond to
L. amazonensis
metacyclic promastigotes and amastigotes derived from axenic cultures or from the lesions of infected mice. Neutrophils efficiently internalized both amastigote and promastigote forms of the parasite, and phagocytosis was enhanced in lipopolysaccharide (LPS)-activated neutrophils or when parasites were opsonized in serum from infected mice. Parasite uptake resulted in neutrophil activation, oxidative burst, and accelerated neutrophil death. While promastigotes triggered the release of tumor necrosis factor alpha (TNF-α), uptake of amastigotes preferentially resulted in the secretion of interleukin-10 (IL-10) from neutrophils. Finally, the majority of promastigotes were killed by neutrophils, while axenic culture- and lesion-derived amastigotes were highly resistant to neutrophil microbicidal mechanisms. This study indicates that neutrophils exhibit distinct responses to promastigote and amastigote infection. Our findings have important implications for determining the impact of sustained neutrophil recruitment and amastigote-neutrophil interactions during the late phase of cutaneous leishmaniasis.
CD30 Is Required for Activation of a Unique Subset of Interleukin-17A-Producing γδ T Cells in Innate Immunity against Mycobacterium bovis Bacillus Calmette-Guérin Infection
Authors: Guo Ying , Sun Xun , Shibata Kensuke , Yamada Hisakata , Muta Hiromi , Podack Eckhard R. , Yoshikai Yasunobu 
Published: August 2013

ABSTRACTInterleukin-17A (IL-17A)-producing γδ T cells are known to be activated followingMycobacterium bovisbacillus Calmette-Guérin (BCG) infection. Here, we show that CD30, a member of the tumor necrosis factor (TNF) receptor superfamily, is important for activation of IL-17A-producing γδ T cells after BCG infection. Vγ1−Vγ4−γδ T cells preferentially expressing Vγ6/Vδ1 genes were identified as the major source of IL-17A in the peritoneal cavity during the early stage of BCG infection. The number of IL-17A-producing Vγ1−Vγ4−γδ T cells bearing Vγ6 increased in peritoneal exudate cells (PEC) of wild-type (WT) mice but not in those of CD30 knockout (KO) mice in response to BCG infection. Consistently, CD30 ligand (CD30L) or CD30 expression, predominantly by Vγ1−Vγ4−γδ T cells, was rapidly upregulated after BCG infection. Inhibition of CD30L/CD30 signaling byin vivoadministration of a soluble CD30 and immunoglobulin fusion protein (CD30-Ig) severely impaired activation of IL-17A-producing Vγ1−Vγ4−γδ T cells in WT mice, while stimulating CD30L/CD30 signaling byin vivoadministration of agonistic anti-CD30 monoclonal antibody (MAb) restored IL-17A production by Vγ1−Vγ4−γδ T cells in CD30L KO mice after BCG infection. These results suggest that CD30 signaling plays an important role in the activation of IL-17A-producing Vγ1−Vγ4−γδ T cells bearing Vγ6 at an early stage of BCG infection.
Contribution of Secretory Antibodies to Intestinal Mucosal Immunity against Helicobacter pylori
Authors: Gorrell Rebecca J. , Wijburg Odilia L. C. , Pedersen John S. , Walduck Anna K. , Kwok Terry , Strugnell Richard A. , Robins-Browne Roy M. 
Published: August 2013

ABSTRACTThe natural immune response toHelicobacter pylorineither clears infection nor prevents reinfection. However, the ability of secretory antibodies to influence the course ofH. pyloriinfection has not been determined. We compared the natural progression ofH. pyloriinfection in wild-type C57BL/6 mice with that in mice lacking the polymeric immunoglobulin receptor (pIgR) that is essential for the secretion of polymeric antibody across mucosal surfaces.H. pyloriSS1-infected wild-type and pIgR knockout (KO) mice were sampled longitudinally for gastrointestinal bacterial load, antibody response, and histological changes. The gastric bacterial loads of wild-type and pIgR KO mice remained constant and comparable at up to 3 months postinfection (mpi) despite SS1-reactive secretory IgA in the intestinal contents of wild-type mice at that time. Conversely, abundant duodenal colonization of pIgR KO animals contrasted with the near-total eradication ofH. pylorifrom the intestine of wild-type animals by 3 mpi.H. pyloriwas cultured only from the duodenum of those animals in which colonization in the distal gastric antrum was of sufficient density for immunohistological detection. By 6 mpi, the gastric load ofH. pyloriin wild-type mice was significantly lower than in pIgR KO animals. While there was no corresponding difference between the two mouse strains in gastric pathology results at 6 mpi, reductions in gastric bacterial load correlated with increased gastric inflammation together with an intestinal secretory antibody response in wild-type mice. Together, these results suggest that naturally produced secretory antibodies can modulate the progress ofH. pyloriinfection, particularly in the duodenum.
Compensatory Mutants of the Bovine Papillomavirus E5 Protein and the Platelet-Derived Growth Factor β Receptor Reveal a Complex Direct Transmembrane Interaction
Authors: Edwards Anne P. B. , Xie Yanhua , Bowers Lara , DiMaio Daniel 
Published: August 2013

ABSTRACT
The 44-amino-acid E5 protein of bovine papillomavirus is a dimeric transmembrane protein that exists in a stable complex with the platelet-derived growth factor (PDGF) β receptor, causing receptor activation and cell transformation. The transmembrane domain of the PDGF β receptor is required for complex formation, but it is not known if the two proteins contact one another directly. Here, we studied a PDGF β receptor mutant containing a leucine-to-isoleucine substitution in its transmembrane domain, which prevents complex formation with the wild-type E5 protein in mouse BaF3 cells and inhibits receptor activation by the E5 protein. We selected E5 mutants containing either a small deletion or multiple substitution mutations that restored binding to the mutant PDGF β receptor, resulting in receptor activation and growth factor independence. These E5 mutants displayed lower activity with PDGF β receptor mutants containing other transmembrane substitutions in the vicinity of the original mutation, and one of them cooperated with a receptor mutant containing a distal mutation in the juxtamembrane domain. These results provide strong genetic evidence that the transmembrane domains of the E5 protein and the PDGF β receptor contact one another directly. They also demonstrate that different mutations in the E5 protein allow it to tolerate the same mutation in the PDGF β receptor transmembrane domain and that a mutation in the E5 protein can allow it to tolerate different mutations in the PDGF β receptor. Thus, the rules governing direct interactions between transmembrane helices are complex and not restricted to local interactions.
Anomalous Dispersion of the S1 Lamb Mode
Authors: Ahmad Faiz , Hussain Takasar 
Published: August 2013

The S1 mode of the Lamb spectrum of an isotropic plate exhibits negative group velocity in a narrow frequency domain. This anomalous behavior is explained analytically by examining the slope of each mode first in its initial state and then near its turning points.Erratum to “Anomalous Dispersion of the S1 Lamb Mode”
Long-Term Survival in Primary Glioblastoma With Versus Without Isocitrate Dehydrogenase Mutations
Authors: Hartmann Christian , Hentschel Bettina , Simon Matthias , Westphal Manfred , Schackert Gabriele , Tonn Jörg C. , Loeffler Markus , Reifenberger Guido , Pietsch Torsten , von Deimling Andreas , Weller Michael ,   for the German Glioma Network
Published: August 2013

Abstract
Purpose: The determinants of long-term survival in glioblastoma have remained largely obscure. Isocitrate dehydrogenase (IDH) 1 or 2 mutations are common in World Health Organization (WHO) grades II and III gliomas, but rare in primary glioblastomas, and associated with longer survival.
Experimental Design: We compared clinical and molecular characteristics of 69 patients with centrally confirmed glioblastoma and survival &gt;36 months (LTS-36), including 33 patients surviving &gt;60 months (LTS-60), with 257 patients surviving &lt;36 months. MGMT promoter methylation, 1p/19q codeletions, EGFR amplification, TP53 mutations, and IDH1/2 mutations were determined by standard techniques.
Results: The rate of IDH1/2 mutations in LTS-36 patients was 34% (23 of 67 patients) as opposed to 4.3% in controls (11 of 257 patients). Long-term survivors with IDH1/2-mutant glioblastomas were younger, had almost no EGFR amplifications, but exhibited more often 1p/19q codeletions and TP53 mutations than LTS patients with IDH1/2 wild-type glioblastomas. Long-term survivors with IDH1/2 wild-type showed no distinguishing features from other patients with IDH1/2 wild-type glioblastomas except for a higher rate of MGMT promoter methylation. Similarly, among 11 patients with IDH1/2-mutant glioblastomas without long-term survival, the only difference to IDH1/2-mutant long-term survivors was less-frequent MGMT promoter methylation. Compared with LTS-36 patients, LTS-60 patients had less frequently TP53 mutations and radiotherapy alone as initial treatment.
Conclusions: IDH1/2 mutations define a subgroup of tumors of LTS patients that exhibit molecular characteristics of WHO grade II/III gliomas and secondary glioblastomas. Determinants of LTS with IDH1/2 wild-type glioblastomas, which exhibit typical molecular features of primary glioblastomas, beyond MGMT promoter methylation, remain to be identified. Clin Cancer Res; 19(18); 5146–57. ©2013 AACR.
TMPRSS2-ERG Status Is Not Prognostic Following Prostate Cancer Radiotherapy: Implications for Fusion Status and DSB Repair
Authors: Dal Pra Alan , Lalonde Emilie , Sykes Jenna , Warde Fiona , Ishkanian Adrian , Meng Alice , Maloff Chad , Srigley John , Joshua Anthony M. , Petrovics Gyorgy , van der Kwast Theodorus , Evans Andrew , Milosevic Michael , Saad Fred , Collins Colin , Squire Jeremy , Lam Wan , Bismar Tarek A. , Boutros Paul C. , Bristow Robert G. 
Published: August 2013

Abstract
Background: Preclinical data suggest that TMPRSS2-ERG gene fusions, present in about 50% of prostate cancers, may be a surrogate for DNA repair status and therefore a biomarker for DNA-damaging agents. To test this hypothesis, we examined whether TMPRSS2-ERG status was associated with biochemical failure after clinical induction of DNA damage following image-guided radiotherapy (IGRT).
Methods: Pretreatment biopsies from two cohorts of patients with intermediate-risk prostate cancer [T1/T2, Gleason score (GS) &lt; 8, prostate-specific antigen (PSA) &lt; 20 ng/mL; &gt;7 years follow-up] were analyzed: (i) 126 patients [comparative genomic hybridization (CGH) cohort] with DNA samples assayed by array CGH (aCGH) for the TMPRSS2-ERG fusion; and (ii) 118 patients [immunohistochemical (IHC) cohort] whose biopsy samples were scored within a defined tissue microarray (TMA) immunostained for ERG overexpression (known surrogate for TMPRSS2-ERG fusion). Patients were treated with IGRT with a median dose of 76 Gy. The potential role of TMPRSS2-ERG status as a prognostic factor for biochemical relapse-free rate (bRFR; nadir + 2 ng/mL) was evaluated in the context of clinical prognostic factors in multivariate analyses using a Cox proportional hazards model.
Results: TMPRSS2-ERG fusion by aCGH was identified in 27 (21%) of the cases in the CGH cohort, and ERG overexpression was found in 59 (50%) patients in the IHC cohort. In both cohorts, TMPRSS2-ERG status was not associated with bRFR on univariate or multivariate analysis.
Conclusions: In two similarly treated IGRT cohorts, TMPRSS2-ERG status was not prognostic for bRFR, in disagreement with the hypothesis that these prostate cancers have DNA repair defects that render them clinically more radiosensitive. TMPRSS2-ERG is therefore unlikely to be a predictive factor for IGRT response. Clin Cancer Res; 19(18); 5202–9. ©2013 AACR.
Lysophosphatidic Acid Inhibits CD8 T-cell Activation and Control of Tumor Progression
Authors: Oda Shannon K. , Strauch Pamela , Fujiwara Yuko , Al-Shami Amin , Oravecz Tamas , Tigyi Gabor , Pelanda Roberta , Torres Raul M. 
Published: August 2013

AbstractCD8 T lymphocytes are able to eliminate nascent tumor cells through a process referred to as immunosurveillance. However, multiple inhibitory mechanisms within the tumor microenvironment have been described that impede tumor rejection by CD8 T cells, including increased signaling by inhibitory receptors. Lysophosphatidic acid (LPA) is a bioactive lysophospholipid that has been shown repeatedly to promote diverse cellular processes benefiting tumorigenesis. Accordingly, the exaggerated expression of LPA and LPA receptors is a common feature of diverse tumor cell lineages and can result in elevated systemic LPA levels. LPA is recognized by at least six distinct G protein–coupled receptors, several of which are expressed by T cells, although the precise function of LPA signaling in CD8 T-cell activation and function has not been defined. Here, we show that LPA signaling via the LPA5 receptor expressed by CD8 T cells suppresses antigen receptor signaling, cell activation, and proliferation in vitro and in vivo. Importantly, in a mouse melanoma model tumor-specific CD8 T cells that are LPA5-deficient are able to control tumor growth significantly better than wild-type tumor-specific CD8 T cells. Together, these data suggest that the production of LPA by tumors serves not only in an autocrine manner to promote tumorigenesis, but also as a mechanism to suppress adaptive immunity and highlights a potential novel target for cancer treatment. Cancer Immunol Res; 1(4); 245–55. ©2013 AACR.
The Governing Dynamics of the Secondary Eyewall Formation of Typhoon Sinlaku (2008)
Authors: Sun Y. Qiang , Jiang Yuxin , Tan Benkui , Zhang Fuqing 
Published: August 2013

Abstract
Through successful convection-permitting simulations of Typhoon Sinlaku (2008) using a high-resolution nonhydrostatic model, this study examines the role of peripheral convection in the storm's secondary eyewall formation (SEF) and its eyewall replacement cycle (ERC). The study demonstrates that before SEF the simulated storm intensifies via an expansion of the tangential winds and an increase in the boundary layer inflow, which are accompanied by peripheral convective cells outside the primary eyewall. These convective cells, which initially formed in the outer rainbands under favorable environmental conditions and move in an inward spiral, play a crucial role in the formation of the secondary eyewall. It is hypothesized that SEF and ERC ultimately arise from the convective heating released from the inward-moving rainbands, the balanced response in the transverse circulation, and the unbalanced dynamics in the atmospheric boundary layer, along with the positive feedback between these processes.
Atmospheric Rivers and Flooding over the Central United States
Authors: Lavers David A. , Villarini Gabriele 
Published: August 2013

Abstract
This paper undertakes a hydrometeorological analysis of flood events in the central United States. Vertically integrated horizontal water vapor transport over 1979–2011 is calculated in the ECMWF Interim Re-Analysis (ERA-Interim) and used in an algorithm to identify episodes of high moisture transport, or atmospheric rivers (ARs), over the central United States. The AR events are almost evenly divided among the seasons (143 during the winter, 144 during the spring, and 124 during the fall), with a minimum (40) during the summer. The annual maxima (AM) floods from 1105 basins over the period 1980–2011 are used as a measure of the hydrologic impact of the AR events. Of these basins, 470 (or 42.5%) had more than 50% of their AM floods linked to ARs. Furthermore, 660 of the 1105 basins (59.7%) had 5 or more of their top 10 AM floods related to ARs, indicating that ARs control the upper tail of the flood peak distribution over large portions of the study area. The seasonal composite average of mean sea level pressure anomalies associated with the ARs shows a trough located over the central United States and a ridge over the U.S. East Coast, leading to southerly winds and the advection of moisture over the study region. Based on the findings of this study, ARs are a major flood agent over the central United States.
Development of a Mesoscale Ensemble Data Assimilation System at the Naval Research Laboratory
Authors: Zhao Qingyun , Zhang Fuqing , Holt Teddy , Bishop Craig H. , Xu Qin 
Published: August 2013

Abstract
An ensemble Kalman filter (EnKF) has been adopted and implemented at the Naval Research Laboratory (NRL) for mesoscale and storm-scale data assimilation to study the impact of ensemble assimilation of high-resolution observations, including those from Doppler radars, on storm prediction. The system has been improved during its implementation at NRL to further enhance its capability of assimilating various types of meteorological data. A parallel algorithm was also developed to increase the system’s computational efficiency on multiprocessor computers. The EnKF has been integrated into the NRL mesoscale data assimilation system and extensively tested to ensure that the system works appropriately with new observational data stream and forecast systems. An innovative procedure was developed to evaluate the impact of assimilated observations on ensemble analyses with no need to exclude any observations for independent validation (as required by the conventional evaluation based on data-denying experiments). The procedure was employed in this study to examine the impacts of ensemble size and localization on data assimilation and the results reveal a very interesting relationship between the ensemble size and the localization length scale. All the tests conducted in this study demonstrate the capabilities of the EnKF as a research tool for mesoscale and storm-scale data assimilation with potential operational applications.
Patient satisfaction with participation in a randomized exercise trial: Effects of randomization and a usual care posttrial exercise program
Authors: Courneya Kerry S , Forbes Cynthia C , Trinh Linda , Sellar Christopher M , Friedenreich Christine M , Reiman Tony 
Published: August 2013

Background Participation in an exercise trial is a major commitment for cancer survivors, but few exercise trials have evaluated patient satisfaction with trial participation. Purpose To examine patient satisfaction with participation in the Healthy Exercise for Lymphoma Patients (HELP) Trial and to explore possible determinants. Methods The HELP Trial randomized 122 lymphoma patients to 12 weeks of supervised aerobic exercise training (AET; n = 60) or to usual care (UC; n = 62), with the option of participating in a 4-week posttrial exercise program. At the 6-month follow-up assessment, participants evaluated their overall trial satisfaction. Results Personal satisfaction with trial participation was strongly influenced by group assignment with participants randomized to AET reporting participation to be more rewarding (p < 0.001) and personally useful (p < 0.001) than participants randomized to UC. UC participants who completed the optional 4-week posttrial exercise program reported participation to be more rewarding (p = 0.008) and personally useful (p < 0.001) than UC participants who declined the program. Limitations The study is limited by the lack of a validated measure of participant satisfaction, and the fact that the offer of participation in the posttrial exercise program to the UC group was not randomized. Conclusions Lymphoma patients randomized to UC viewed it as less rewarding and personally useful despite being offered a 4-week posttrial exercise program. UC participants who completed the 4-week program reported personal satisfaction levels similar to the AET group; however, the causal direction of this association is unknown. Researchers should continue to evaluate participant satisfaction in exercise trials.
The English North-South divide: risk factors for cardiovascular disease accounting for cross-sectional socio-economic position
Authors: Kumar Raekha , Dalton Andrew RH 
Published: August 2013

Aims: Given a North-South divide in mortality in England, we aimed to assess the extent of a North-South divide in risk factors for cardiovascular disease (CVD), controlling for markers of socio-economic position (SEP). Methods: We undertook cross-sectional analyses using respondents from the 2006 Health Survey for England. We assessed mean systolic blood pressure, total cholesterol, body mass index (BMI) and smoking prevalence in the two regions. We built nested regression models adding demographic factors, SEP indicators, behavioural risk factors, vascular disease status and CVD preventive medications stepwise into each model. We examined interactions between region, age and gender. Results: Controlling for demographic variables, we found a northern excess in systolic blood pressure (+1.95mmHg (SE = 0.40)), BMI (0.40kgm-2 (SE = 0.12)) and smoking prevalence (5.6% (SE = 1.1)). The difference in smoking prevalence was entirely abolished by markers of SEP. Systolic blood pressure and BMI differences were attenuated by SEP, behavioural and disease indicators, but remained (+1.63mmHg (SE = 0.41) and 0.25kgm-2 (SE = 0.12), respectively). However, they were lost after adjustment for preventive medication. The North-South divide in systolic blood pressure was attributed to differences in men and younger-to-middle-aged groups. Northern respondents were more physically active, especially younger men. Conclusions: English North-South differences in smoking can be explained through adverse, cross-sectional SEP. Northern excesses in blood pressure and BMI may be associated with differential clinical management. Risk factor differences may, in part, explain a previously found North-South divide in mortality. Further exploration of geographic inequalities, concentrating on the impact of healthcare, may be warranted.