bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Monocytes Promote Th1 and Th17 Responses to Streptococcus pneumoniae
Authors: Olliver Marie , Hiew Jeffni , Mellroth Peter , Henriques-Normark Birgitta , Bergman Peter 
Published: July 2011

ABSTRACT

Streptococcus pneumoniae
is a leading cause of bacterial pneumonia, meningitis, and sepsis in children. Human immunity to pneumococcal infections has been assumed to depend on anticapsular antibodies. However, recent findings from murine models suggest that alternative mechanisms, dependent on T helper cells, are also involved. Although the immunological events in which T helper cells contribute to acquired immunity have been studied in mice, little is known about how these responses are generated in humans. Therefore, we examined bacterial and host factors involved in the induction of Th1 and Th17 responses, using a coculture model of human monocytes and CD4
+
T cells. We show that monocytes promote effector cytokine production by memory T helper cells, leading to a mixed Th1/Th17 (gamma interferon [IFN-γ]/interleukin-17 [IL-17]) profile. Both T helper cytokines were triggered by purified pneumococcal peptidoglycan; however, the balance between the two immune effector arms depended on bacterial viability. Accordingly, live pneumococci triggered a Th1-biased response via monocyte production of IL-12p40, whereas heat-killed pneumococci triggered a Th17 response through TLR2 signaling. An increased understanding of human T helper responses is essential for the development of novel pneumococcal vaccines designed to elicit cell-mediated immunity.
Cyclic Dimeric GMP Signaling Regulates Intracellular Aggregation, Sessility, and Growth of Ehrlichia chaffeensis
Authors: Kumagai Yumi , Matsuo Junji , Cheng Zhihui , Hayakawa Yoshihiro , Rikihisa Yasuko 
Published: July 2011

ABSTRACT

Cyclic dimeric GMP (c-di-GMP), a bacterial second messenger, is known to regulate bacterial biofilm and sessility. Replication of an obligatory intracellular pathogen,
Ehrlichia chaffeensis
, is characterized by formation of bacterial aggregates called morulae inside membrane-bound inclusions. When
E. chaffeensis
matures into an infectious form, morulae become loose to allow bacteria to exit from host cells to infect adjacent cells.
E. chaffeensis
expresses a sensor kinase, PleC, and a cognate response regulator, PleD, which can produce c-di-GMP. A hydrophobic c-di-GMP antagonist, 2′-
O
-di(
tert
-butyldimethysilyl)-c-di-GMP (CDGA) inhibits
E. chaffeensis
internalization into host cells by facilitating degradation of some bacterial surface proteins via endogenous serine proteases. In the present study, we found that PleC and PleD were upregulated synchronously during exponential growth of bacteria, concomitant with increased morula size. While CDGA did not affect host cells, when infected cells were treated with CDGA, bacterial proliferation was inhibited, morulae became less compact, and the intracellular movement of bacteria was enhanced. Concurrently, CDGA treatment facilitated the extracellular release of bacteria with lower infectivity than those spontaneously released from sham-treated cells. Addition of CDGA to isolated inclusions induced dispersion of the morulae, degradation of an inclusion matrix protein TRP120, and bacterial intrainclusion movement, all of which were blocked by a serine protease inhibitor. These results suggest that c-di-GMP signaling regulates aggregation and sessility of
E. chaffeensis
within the inclusion through stabilization of matrix proteins by preventing the serine protease activity, which is associated with bacterial intracellular proliferation and maturation.
Functional Characterization of EpsC, a Component of the Type II Secretion System, in the Pathogenicity of Vibrio vulnificus
Authors: Hwang Won , Lee Na Yeon , Kim Juri , Lee Mi-Ae , Kim Kun-Soo , Lee Kyu-Ho , Park Soon-Jung 
Published: July 2011

ABSTRACT

EpsC, one of the components comprising the type II secretion system (T2SS), was isolated from a human-pathogenic bacterium,
Vibrio vulnificus
, to evaluate its role in eliciting virulence. An
espC
-deleted mutant of
V. vulnificus
displayed a reduced cytotoxicity to the human cell line HEp-2 and an attenuated virulence in a mouse model. This mutant exhibited dramatic defects in the secretion of diverse extracellular proteins, such as outer membrane proteins, transporters, and the known secreted factors, notably, a hemolysin (VvhA) and an elastase (VvpE). A defect in its secretion of proteins was restored by in
trans
complementation of the intact
epsC
gene. Analyses of cellular fractions revealed that VvhA and VvpE of the
ΔepsC
mutant were not excreted outside the cell but were present mainly in the periplasmic space. Examination of a
V. vulnificus
mutant deficient in TolC, a component of the T1SS, showed that it is not involved in the secretion of VvhA and VvpE but that it is necessary for the secretion of another major toxin of
V. vulnificus
, RtxA. Therefore, the T2SS is required for
V. vulnificus
pathogenicity, which is mediated by at least two secreted factors, VvhA and VvpE, via facilitating the secretion and exposure of these factors to host cells.
Laboratory testing and microanalysis of colloidal mobilization from a glacial till
Authors: Kunberger T. , Gabr M.A. 
Published: July 2011

The effect of the dispersion and piping of clay fines — colloid mobilization — as a means of remediating subsurface contamination was investigated. Prior colloid mobility research has focused on mitigating colloidal movement to reduce contaminant transport or monitoring colloids to determine the extent of mobility and contamination transport. To date, limited work has been performed to evaluate remediation efficiency associated with the removal of clay-sized (colloidal) particles and related sorbed contamination. Laboratory flow-through tests were performed on a glacial till from a radioactive cesium contaminated site. Post-testing analysis comprised mass balance checks, grain-size distribution testing, and microscopic analysis of removed particles. Results showed the potential of initiating and maintaining clay dispersion and piping, thus establishing a means to mobilize colloids and subsequently remove them from the subsurface environment. Beneficial effects of hydraulic gradient and ionic strength manipulations were influenced by soil properties, such as cation exchange capacity, clay content, and average pore diameter. In general, colloid mobilization testing results found that extreme levels of mobilization typically resulted in particle trapping and an overall reduction in colloidal removal, while the effect of more moderate levels was mobilization with increased rates of removal.
Simple assessment of needleleaf and broadleaf chlorophyll content using a flatbed color scanner
Authors: Eitel Jan U.H. , Vierling Lee A. , Long Dan S. , Litvak Marcy , Eitel Karla C.B. 
Published: July 2011

Total chlorophyll a and b content (Chlab) of leaves is an important indicator of the photosynthetic capacity, nutritional condition, and health status of plants. Developing low-cost, easily accessible methods for estimating foliar Chlabof needleleaf species would enable a broad range of forestry applications. We evaluated data acquired using an off-the-shelf flatbed color scanner to assess its utility in quantifying needleleaf Chlab. Red and green digital numbers (DN) of the scan image were obtained from needle leaves of oneseed juniper ( Juniperus monosperma (Engelm.) Sarg.) and piñon pine ( Pinus edulis Engelm.) in addition to two broadleaf species for comparison purposes. Values of laboratory-determined Chlab(range 1.5–64.0 µg·cm–2) were then predicted using the DN values from the scanner-imaged needle leaves as a regression estimator. The red or green DN values of the scanner-imaged needle leaves were curvilinearly related to Chlabwith an r2of 0.67 (RMSE = 4.72 µg·cm–2, p < 0.001) for juniper needles and an r2of 0.54 (RMSE = 5.51 µg·cm–2, p < 0.001) for pine needles. Although our results suggest that flatbed scanner derived Chlabestimates are not suitable for applications where highly accurate Chlabestimates are required, the technique is likely to be a useful tool for forest practitioners in managing tree nutrition and health.
Does frequent burning affect longleaf pine (Pinus palustris) bark thickness?
Authors: Wang G. Geoff , Wangen Steve R. 
Published: July 2011

Bark thickness plays a critical role in protecting a tree’s cambium from damage by fires. Does frequent surface fire stimulate bark production compared with a fire-suppressed control? Based on data from an ongoing, long-term prescribed fire study, we explored differences in bark thickness from 0 to 200 cm above the ground for longleaf pine ( Pinus palustris P. Mill.) trees on burned and control sites. Biennial prescribed fires, applied between 1973 (stand age = 14 years) and 2006 (stand age = 47 years), significantly reduced diameter at breast height. After adjusting for differences in diameter at breast height, we found no difference in bark thickness of trees from the burn and control sites, except for bark thickness measured at 0 cm aboveground where control sites had significantly thicker bark than burned sites. Results suggest that frequent burning did not stimulate bark production in longleaf pine.
Discrete element textures
Authors: Ma Chongyang , Wei Li-Yi , Tong Xin 
Published: July 2011

A variety of phenomena can be characterized by repetitive small scale elements within a large scale domain. Examples include a stack of fresh produce, a plate of spaghetti, or a mosaic pattern. Although certain results can be produced via manual placement or procedural/physical simulation, these methods can be labor intensive, difficult to control, or limited to specific phenomena.
We present discrete element textures, a data-driven method for synthesizing repetitive elements according to a small input exemplar and a large output domain. Our method preserves both individual element properties and their aggregate distributions. It is also general and applicable to a variety of phenomena, including different dimensionalities, different element properties and distributions, and different effects including both artistic and physically realistic ones. We represent each element by one or multiple samples whose positions encode relevant element attributes including position, size, shape, and orientation. We propose a sample-based neighborhood similarity metric and an energy optimization solver to synthesize desired outputs that observe not only input exemplars and output domains but also optional constraints such as physics, orientation fields, and boundary conditions. As a further benefit, our method can also be applied for editing existing element distributions.
Immune Adjuvant Efficacy of CpG Oligonucleotide in Cancer Treatment Is Founded Specifically upon TLR9 Function in Plasmacytoid Dendritic Cells
Authors: Nierkens Stefan , den Brok Martijn H. , Garcia Zacharias , Togher Susan , Wagenaars Jori , Wassink Melissa , Boon Louis , Ruers Theo J. , Figdor Carl G. , Schoenberger Stephen P. , Adema Gosse J. , Janssen Edith M. 
Published: July 2011

Abstract
The differences in function, location, and migratory pattern of conventional dendritic cells (cDC) and plasmacytoid DCs (pDC) not only point to specialized roles in immune responses but also signify additive and interdependent relationships required to clear pathogens. We studied the in vivo requirement of cross-talk between cDCs and pDCs for eliciting antitumor immunity against in situ released tumor antigens in the absence or presence of the Toll-like receptor (TLR) 9 agonist CpG. Previous data indicated that CpG boosted tumor-specific T-cell responses after in vivo tumor destruction and increased survival after tumor rechallenges. The present study shows that cDCs are indispensable for cross-presentation of ablation-released tumor antigens and for the induction of long-term antitumor immunity. Depletion of pDCs or applying this model in type I IFN receptor–deficient mice abrogated CpG-mediated responses. CD8α+ cDCs and the recently identified merocytic cDCs were dependent on pDCs for CpG-induced upregulation of CD80. Moreover, DC transfer studies revealed that merocytic cDCs and CD8α+ cDCs were most susceptible to pDC help and subsequently promoted tumor-free survival in a therapeutic setting. By transferring wild-type pDCs into TLR9-deficient mice, we finally showed that TLR9 expression in pDCs is sufficient to benefit from CpG as an adjuvant. These studies indicate that the efficacy of CpG in cancer immunotherapy is dependent on cross-talk between pDCs and specific subsets of cDCs. Cancer Res; 71(20); 6428–37. ©2011 AACR.
Bevacizumab Has Differential and Dose-Dependent Effects on Glioma Blood Vessels and Tumor Cells
Authors: von Baumgarten Louisa , Brucker David , Tirniceru Anca , Kienast Yvonne , Grau Stefan , Burgold Steffen , Herms Jochen , Winkler Frank 
Published: July 2011

Abstract
Purpose: Bevacizumab targets VEGF-A and has proved beneficial in glioma patients, improving clinical symptoms by the reduction of tumor edema. However, it remains controversial whether or not bevacizumab exerts antitumor effects in addition to (and potentially independent of) its effects on tumor vessels, and it is unknown what doses are needed to achieve this.
Experimental Design: We established a novel orthotopic glioma mouse model that allowed us to simultaneously study the kinetics of the morphologic and functional vascular changes, tumor growth, and the viability of individual tumor cells during the course of anti-VEGF therapy in the same microscopic tumor region in real-time. Three doses of bevacizumab were compared, a subclinical dose and two clinical doses (medium and high).
Results: Low (subclinical) doses of bevacizumab led to a significant reduction of the total vascular volume without affecting tumor cell viability or the overall tumor growth rates. Medium and high doses triggered a similar degree of vascular regression but significantly decreased tumor growth and prolonged survival. Remaining vessels revealed morphologic features of vascular normalization, reduced permeability, and an increase in blood flow velocity; the latter was dose dependent. We observed an uncoupling of the antitumoral and the antivascular effects of bevacizumab with the high dose only, which showed the potential to cause microregional glioma cell regression. In some tumor regions, pronounced glioma cell regression occurred even without vascular regression. In vitro, there was no effect of bevacizumab on glioma cell proliferation.
Conclusions: Regression of glioma cells can occur independently from vascular regression, suggesting that high doses of bevacizumab have indirect anticancer cell properties in vivo. Clin Cancer Res; 17(19); 6192–205. ©2011 AACR.
Metronomic Oral Topotecan with Pazopanib Is an Active Antiangiogenic Regimen in Mouse Models of Aggressive Pediatric Solid Tumor
Authors: Kumar Sushil , Mokhtari Reza Bayat , Sheikh Reihaneh , Wu Bing , Zhang Libo , Xu Ping , Man Shan , Oliveira Indhira Dias , Yeger Herman , Kerbel Robert S. , Baruchel Sylvain 
Published: July 2011

Abstract
Purpose: Low dose metronomic (LDM) chemotherapy, combined with VEGF signaling pathway inhibitors, is a highly effective strategy to coordinately inhibit angiogenesis and tumor growth in many adult preclinical cancer models. We have tested the efficacies of daily oral LDM topotecan alone and in combination with pazopanib, a VEGF receptor inhibitor, in three pediatric extracranial solid tumor mouse models.
Experimental Design: In vitro dose–response study of topotecan and pazopanib was conducted on several neuroblastoma, osteosarcoma, and rhabdomyosarcoma cell lines. In vivo antitumor efficacies of the LDM topotecan and pazopanib as single agents and in combination were tested on 4 subcutaneous xenograft models and on 2 neuroblastoma metastatic models. Circulating angiogenic factors such as circulating endothelial cells (CEC), circulating endothelial pro genitor cells (CEP), and microvessel densities were used as surrogate biomarker markers of antiangiogenic activity.
Results: In vitro, topotecan caused a dose-dependent decrease in viabilities of all cell lines, while pazopanib did not. In vivo, combination of topotecan + pazopanib (TP + PZ) showed significant antitumor activity and significant enhancement in survival compared with the respective single agents in all models. Reductions in viable CEP and/or CEC levels and tumor microvessel density were correlated with tumor response and therefore confirmed the antiangiogenic activity of the regimens. Pharmacokinetic studies of both drugs did not reveal any drug–drug interaction.
Conclusion: Metronomic administration of TP + PZ showed a statistically significant antitumor activity compared with respective single agents in pediatric tumor mouse models and represent a valid option as a maintenance therapy in aggressive pediatric solid tumors. Clin Cancer Res; 17(17); 5656–67. ©2011 AACR.
The genetic basis of platelet responsiveness to clopidogrel
Authors: Fefer Paul , Matetzky Shlomi 
Published: July 2011

SummaryClopidogrel reduces ischaemic complications in a wide range of patients with coronary artery disease. However, there is much inter-individual variation in clopidogrel-induced platelet inhibition, and a substantial proportion of patients will exhibit non-responsiveness to clopidogrel. Multiple studies have demonstrated an association between the presence of genetic polymorphisms associated with suboptimal clopidogrel-active metabolite generation, decreased platelet responsiveness, and adverse clinical outcomes. However, it is not clear to what extent the genetic polymorphisms account for the observed variability in response to clopidogrel. In this review we provide a critical summary of the available evidence linking genetic factors with response to clopidogrel, and discuss the clinical implications of this association.
Mitochondrial Transporter ATP Binding Cassette Mitochondrial Erythroid Is a Novel Gene Required for Cardiac Recovery After Ischemia/Reperfusion
Authors: Liesa Marc , Luptak Ivan , Qin Fuzhong , Hyde Brigham B. , Sahin Ergun , Siwik Deborah A. , Zhu Zhengkun , Pimentel David R. , Xu X. Julia , Ruderman Neil B. , Huffman Karl D. , Doctrow Susan R. , Richey Lauren , Colucci Wilson S. , Shirihai Orian S. 
Published: July 2011

Background
Oxidative stress and mitochondrial dysfunction are central mediators of cardiac dysfunction after ischemia/reperfusion. ATP binding cassette mitochondrial erythroid (ABC-me; ABCB10; mABC2) is a mitochondrial transporter highly induced during erythroid differentiation and predominantly expressed in bone marrow, liver, and heart. Until now, ABC-me function in heart was unknown. Several lines of evidence demonstrate that the yeast ortholog of ABC-me protects against increased oxidative stress. Therefore, ABC-me is a potential modulator of the outcome of ischemia/reperfusion in the heart.

Methods and Results

Mice harboring 1 functional allele of ABC-me (ABC-me
+/−
) were generated by replacing ABC-me exons 2 and 3 with a neomycin resistance cassette. Cardiac function was assessed with Langendorff perfusion and echocardiography. Under basal conditions, ABC-me
+/−
mice had normal heart structure, hemodynamic function, mitochondrial respiration, and oxidative status. However, after ischemia/reperfusion, the recovery of hemodynamic function was reduced by 50% in ABC-me
+/−
hearts as a result of impairments in both systolic and diastolic function. This reduction was associated with impaired mitochondrial bioenergetic function and with oxidative damage to both mitochondrial lipids and sarcoplasmic reticulum calcium ATPase after reperfusion. Treatment of ABC-me
+/−
hearts with the superoxide dismutase/catalase mimetic EUK-207 prevented oxidative damage to mitochondria and sarcoplasmic reticulum calcium ATPase and restored mitochondrial and cardiac function to wild-type levels after reperfusion.

Conclusions
Inactivation of 1 allele of ABC-me increases the susceptibility to oxidative stress induced by ischemia/reperfusion, leading to increased oxidative damage to mitochondria and sarcoplasmic reticulum calcium ATPase and to impaired functional recovery. Thus, ABC-me is a novel gene that determines the ability to tolerate cardiac ischemia/reperfusion.
Sports-Related Sudden Death in the General Population
Authors: Marijon Eloi , Tafflet Muriel , Celermajer David S. , Dumas Florence , Perier Marie-Cécile , Mustafic Hazrije , Toussaint Jean-François , Desnos Michel , Rieu Michel , Benameur Nordine , Le Heuzey Jean-Yves , Empana Jean-Philippe , Jouven Xavier 
Published: July 2011

Background—
Although such data are available for young competitive athletes, the prevalence, characteristics, and outcome of sports-related sudden death have not been assessed previously in the general population.

Methods and Results—

A prospective and comprehensive national survey was performed throughout France from 2005 to 2010, involving subjects 10 to 75 years of age. Case detection for sports-related sudden death, including resuscitated cardiac arrest, was undertaken via national ambulance service reporting and Web-based screening of media releases. The overall burden of sports-related sudden death was 4.6 cases per million population per year, with 6% of cases occurring in young competitive athletes. Sensitivity analyses used to address suspected underreporting demonstrated an incidence ranging from 5 to 17 new cases per million population per year. More than 90% of cases occurred in the context of recreational sports. The age of subjects was relatively young (mean±SD 46±15 years), with a predominance of men (95%). Although most cases were witnessed (93%), bystander cardiopulmonary resuscitation was only commenced in 30.7% of cases. Bystander cardiopulmonary resuscitation (odds ratio 3.73, 95% confidence interval 2.19 to 6.39,
P
<0.0001) and initial use of cardiac defibrillation (odds ratio 3.71, 95% confidence interval 2.07 to 6.64,
P
<0.0001) were the strongest independent predictors for survival to hospital discharge (15.7%, 95% confidence interval 13.2% to 18.2%).

Conclusions—
Sports-related sudden death in the general population is considerably more common than previously suspected. Most cases are witnessed, yet bystander cardiopulmonary resuscitation was only initiated in one third of cases. Given the often predictable setting of sports-related sudden death and that prompt interventions were significantly associated with improved survival, these data have implications for health services planning.