bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monocyte Chemoattractant Protein 1 Regulates Pulmonary Host Defense via Neutrophil Recruitment during Escherichia coli Infection
Authors: Balamayooran Gayathriy , Batra Sanjay , Balamayooran Theivanthiran , Cai Shanshan , Jeyaseelan Samithamby 
Published: April 2011

ABSTRACTNeutrophil accumulation is a critical event to clear bacteria. Since uncontrolled neutrophil recruitment can cause severe lung damage, understanding neutrophil trafficking mechanisms is important to attenuate neutrophil-mediated damage. While monocyte chemoattractant protein 1 (MCP-1) is known to be a monocyte chemoattractant, its role in pulmonary neutrophil-mediated host defense against Gram-negative bacterial infection is not understood. We hypothesized that MCP-1/chemokine (C-C motif) ligand 2 is important for neutrophil-mediated host defense. Reduced bacterial clearance in the lungs was observed in MCP-1−/−mice followingEscherichia coliinfection. Neutrophil influx, along with cytokines/chemokines, leukotriene B4(LTB4), and vascular cell adhesion molecule 1 levels in the lungs, was reduced in MCP-1−/−mice after infection.E. coli-induced activation of NF-κB and mitogen-activated protein kinases in the lung was also reduced in MCP-1−/−mice. Administration of intratracheal recombinant MCP-1 (rMCP-1) to MCP-1−/−mice induced pulmonary neutrophil influx and cytokine/chemokine responses in the presence or absence ofE. coliinfection. Ourin vitromigration experiment demonstrates MCP-1-mediated neutrophil chemotaxis. Notably, chemokine receptor 2 is expressed on lung and blood neutrophils, which are increased uponE. coliinfection. Furthermore, our findings show that neutrophil depletion impairsE. coliclearance and that exogenous rMCP-1 after infection improves bacterial clearance in the lungs. Overall, these new findings demonstrate thatE. coli-induced MCP-1 causes neutrophil recruitment directly via chemotaxis as well as indirectly via modulation of keratinocyte cell-derived chemokine, macrophage inflammatory protein 2, and LTB4.
Estradiol and Progesterone Strongly Inhibit the Innate Immune Response of Mononuclear Cells in Newborns
Authors: Giannoni Eric , Guignard Laurence , Knaup Reymond Marlies , Perreau Matthieu , Roth-Kleiner Matthias , Calandra Thierry , Roger Thierry 
Published: April 2011

ABSTRACTNewborns are particularly susceptible to bacterial infections due to qualitative and quantitative deficiencies of the neonatal innate immune system. However, the mechanisms underlying these deficiencies are poorly understood. Given that fetuses are exposed to high concentrations of estradiol and progesterone during gestation and at time of delivery, we analyzed the effects of these hormones on the response of neonatal innate immune cells to endotoxin, bacterial lipopeptide, andEscherichia coliand group BStreptococcus, the two most common causes of early-onset neonatal sepsis. Here we show that at concentrations present in umbilical cord blood, estradiol and progesterone are as powerful as hydrocortisone for inhibition of cytokine production by cord blood mononuclear cells (CBMCs) and newborn monocytes. Interestingly, CBMCs and newborn monocytes are more sensitive to the effects of estradiol and progesterone than adult peripheral blood mononuclear cells and monocytes. This increased sensitivity is associated with higher expression levels of estrogen and membrane progesterone receptors but is independent of a downregulation of Toll-like receptor 2 (TLR2), TLR4, and myeloid differentiation primary response gene 88 in newborn cells. Estradiol and progesterone mediate their anti-inflammatory activity through inhibition of the NF-κB pathway but not the mitogen-activated protein kinase pathway in CBMCs. Altogether, these results suggest that elevated umbilical cord blood concentrations of estradiol and progesterone acting on mononuclear cells expressing high levels of steroid receptors contribute to impair innate immune responses in newborns. Therefore, intrauterine exposure to estradiol and progesterone may participate in increasing susceptibility to infection during the neonatal period.
Placental Malaria-Associated Suppression of Parasite-Specific Immune Response in Neonates Has No Major Impact on Systemic CD4 T Cell Homeostasis
Authors: Soulard Valérie , Amadoudji Zin Martin , Fitting Catherine , Ibitokou Samad , Oesterholt Mayke , Luty Adrian J. F. , Perrin René-Xavier , Massougbodji Achille , Deloron Philippe , Bandeira Antonio , Fievet Nadine 
Published: April 2011

ABSTRACT

In areas where
Plasmodium falciparum
is endemic, pregnancy is associated with accumulation of infected red blood cells (RBCs) in the placenta, a condition referred to as placental malaria (PM). Infants born to PM-positive mothers are at an increased risk of malaria, which is putatively related to the transplacental passage of parasite-derived antigens, with consequent tolerization of the fetal immune system. Here we addressed the impact of PM on the regulation of neonatal T cell responses. We found that the frequency of regulatory CD25
+
CD127
−/low
Foxp3
+
CD4
+
T cells was significantly decreased in neonates born to mothers with high levels of
P. falciparum
-induced placental inflammation, consisting mainly of primigravid mothers. However, at the individual level, the ratio between regulatory and effector (CD25
+
CD127
+
Foxp3
−
) CD4
+
T cells was unaffected by PM. In addition, parasite-induced CD4
+
T cell activation and production of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and IL-10 were strongly reduced in neonates born to PM-positive mothers. Thus, our results show that active PM at delivery is associated with a marked suppression of
P. falciparum
-specific cellular neonatal immune responses, affecting secretion of both pro- and anti-inflammatory cytokines. Additionally, our results suggest that, as in adults, effector and regulatory CD4
+
T cell populations are tightly coregulated in all neonates, irrespective of the maternal infection status.
Critical Role for CXC Ligand 10/CXC Receptor 3 Signaling in the Murine Neonatal Response to Sepsis
Authors: Cuenca Alex G. , Wynn James L. , Kelly-Scumpia Kindra M. , Scumpia Philip O. , Vila Lizette , Delano Matthew J. , Mathews Clayton E. , Wallet Shannon M. , Reeves Westley H. , Behrns Kevin E. , Nacionales Dina C. , Efron Philip A. , Kunkel Steven L. , Moldawer Lyle L. 
Published: April 2011

ABSTRACTPrevious studies have suggested that neonates rely heavily on innate immunity for their antimicrobial response to bacterial infections. However, the innate immune response by neonates to bacterial infection remains poorly characterized. Here, we show that in a murine model of neonatal polymicrobial sepsis, CXC ligand 10 (CXCL10) concentrations increase in the blood and peritoneum concordant with the peritoneal recruitment of granulocytes and macrophages. Additionally, CXC receptor 3 (CXCR3) expression on elicited peritoneal macrophages and granulocytes increases following sepsis. Blockade of CXCL10 worsens not only recruitment and phagocytic function of peritoneal granulocytes and macrophages but also survival. Deletion of CXCR3 also significantly increases mortality to a septic challenge. Finally, we demonstrate that the protective adjuvant effect of pretreatment with a Toll-like receptor 4 agonist to neonatal sepsis is dependent on an endogenous CXCL10 response and that pretreatment of neonates with CXCL10 can also significantly improve macrophage and granulocyte function and modestly improve outcome to polymicrobial sepsis. Together, these data suggest a critical role for CXCL10 signaling during neonatal sepsis.
Environmental and fishing limitations to the rebuilding of the northern Gulf of St. Lawrence cod stock (Gadus morhua)
Authors: Lambert Yvan 
Published: April 2011

Time series of life history traits determining the reproductive potential and productivity of Atlantic cod ( Gadus morhua ) in the northern Gulf of St. Lawrence (nGSL) were obtained for the period covering the collapse and failure of the stock to recover. Decreasing trends in these traits were observed under unfavourable oceanographic conditions, with lowest values reached in the early 1990s. These changes had a negative impact on reproductive rate and instantaneous rate (r) of population growth. Estimates of r used as a proxy of stock productivity were negative when the stock collapsed, indicating that the biomass would have decreased even without fishing. Population abundance projections for the recent period suggest a potential increase in population size of 7.3% per year, with a doubling time of 10.5 years in the absence of exploitation and a near 0% rate with current fishing mortality, indicating that present harvesting does not allow any rebuilding of the stock. Given the similarities in environmental conditions and key life history traits, the situation in the nGSL might reflect the state of many northwest Atlantic cod stocks.
Water chemistry and dissolved organic carbon trends in lakes from Canada’s Atlantic Provinces: no recovery from acidification measured after 25 years of lake monitoring
Authors: Clair Thomas A. , Dennis Ian F. , Vet Robert 
Published: April 2011

We analyzed chemistry trends for 66 Atlantic Canada lakes using data collected from 1983 to 2007, as well as from 1990 to 2007 and 2000 to 2007 for the original 66 and a further 25 lakes that were later added to the network. Though receiving the lowest acid deposition in eastern North America, the region’s waters are seriously affected by acid rain because of poorly buffering soils and bedrock. Earlier work had shown that despite large decreases in sulfate deposition, lake pH and calculated acid neutralization capacity (ANCc) had not increased as they had elsewhere in North America and Europe. Despite a 50% decrease in acid deposition, a further 10 years of lake chemistry data showed a regional increase in ANCc only at the beginning of the sampling period but no increase since the early 1990s. There were also no increases in pH and base cations in the region’s lakes. We show a regional increase in Gran titration ANC (ANCG) from 2000 to the present, which we ascribe to increases in dissolved organic carbon that is probably due to a regional increase in annual air temperatures.
Stonebraker on data warehouses
Authors: Stonebraker Michael 
Published: April 2011

The
Communications
Web site, http://cacm.acm.org, features more than a dozen bloggers in the BLOG@CACM community. In each issue of
Communications
, we'll publish selected posts or excerpts.

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Follow us on Twitter at http://twitter.com/blogCACM
http://cacm.acm.org/blogs/blog-cacm
Data warehouses are not only increasing in size and complexity, but also in their importance to business. Michael Stonebraker shares 10 key ideas on the topic.
DevilTyper
Authors: Ho Chien-Ju , Wu Chen-Chi , Chen Kuan-Ta , Lei Chin-Laung 
Published: April 2011

CAPTCHA is an effective and widely used solution for preventing computer programs (i.e., bots) from performing automated but often malicious actions, such as registering thousands of free email accounts or posting advertisement on Web blogs. To make CAPTCHAs robust to automatic character recognition techniques, the text in the tests are often distorted, blurred, and obscure. At the same time, those robust tests may prevent genuine users from telling the text easily and thus distribute the cost of crime prevention among all the users. Thus, we are facing a dilemma, that is, a CAPTCHA should be robust enough so that it cannot be broken by programs, but also needs to be easy enough so that users need not to repeatedly take tests because of wrong guesses.
In this article, we attempt to resolve the dilemma by proposing a human computation game for quantifying the usability of CAPTCHAs. In our game, DevilTyper, players try to defeat as many devils as possible by solving CAPTCHAs, and player behavior in completing a CAPTCHA is recorded at the same time. Therefore, we can evaluate CAPTCHAs' usability by analyzing collected player inputs. Since DevilTyper provides entertainment itself, we conduct a large-scale study for CAPTCHAs' usability without the resource overhead required by traditional survey-based studies. In addition, we propose a consistent and reliable metric for assessing usability. Our evaluation results show that DevilTyper provides a fun and efficient platform for CAPTCHA designers to assess their CAPTCHA usability and thus improve CAPTCHA design.
Abstract P5-06-11: Knockdown of Splicing Factor SRp20 Results in Cell Line-Dependent Apoptosis in Breast Cancer Cells
Authors: Ho T-T , Arslan AD , Beck WT , He X. 
Published: April 2011

Abstract
Background: Cancer-specific alternative splicing as well as aberrant splicing factor expression in tumors have been reported (Korner M et al, Am. J. Pathol. 175:461-472, 2009). Splicing factor SRp20 belongs to a family of highly conserved serine-arginine-rich proteins with multiple functions in RNA processing such as spliceosome assembly and alternative splicing (Graveley BR, RNA. 6(9):1197-211, 2000). Materials and Methods: We established stable MDA-MB-231, MCF-7, and T47D cell lines carrying doxycycline (Doxy)-inducible SRp20shRNA and assessed Doxy-induced knockdown (KD) of SRp20 by western blot. We performed cell growth curves in triplicate using the MTT assay to determine the effect of SRp20 KD in these cell lines after Doxy induction of SRp20shRNA, and compared these to controls. For apoptosis assays, we stained SRp20shRNA sublines with Hoechst 33342 and counted apoptotic cells under the microscope. We also carried out western blots to examine the expressions of Bcl-2 and cleaved caspases-3, -6, -7, and -9. Results and Discussion: We found that the expression of SRp20 was upregulated in immortalized human mammary epithelial cells (HMECs), compared to controls, and that the level of SRp20 correlated with the transformation state. Knockdown of SRp20 was seen to be 88%, 58%, and 52% in MDA-MB-231, MCF-7, and T47D cells, respectively. However, SRp20 KD suppressed breast cancer cell growth in a cell line-dependent manner. Cell growth after 7 days was decreased in estrogen receptor-negative (ER-) MDA-MB-231 cells (91.4%), and estrogen receptor-positive (ER+) MCF-7 (73.2%), while SRp20 KD had no effect on growth of ER+ T47D cells. The differences between MCF-7 and T47D were notable, since SRp20 was suppressed by -50% in both lines. We found that the number of apoptotic cells in MDA-MB-231 line remarkably increased after Doxy treatment, indicating that the inhibition of cell growth was due to apoptosis. Further, immunoblot analysis of Bcl-2 and cleaved caspases in MDA-MB-231 cells indicated that the SRp20 KD activates the intrinsic apoptotic pathway in these breast cancer cells. We are presently assessing the expressions of these proteins in MCF-7 and T47D cells and investigating the mechanistic basis for this cell line-dependent effect of SRp20 KD. In summary, we report here a novel finding that inhibition of splicing factor SRp20 inhibits cell growth in some breast cancer cell lines. The intrinsic apoptotic pathway appears to be the main mechanism of cell growth inhibition in these cells. Our results indicate that SRp20 plays a major role in the survival of some breast cancer cell lines. This splicing factor may represent a novel therapeutic target for the treatment of some breast cancers.
(Supported in part by CA40570 and CA138762 from NCI to WTB, in part by IDPH to XH, and in part by UIC)
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-06-11.
Pathogenesis and Consequences of Uniparental Disomy in Cancer
Authors: Makishima Hideki , Maciejewski Jaroslaw P. 
Published: April 2011

Abstract
The systematic application of new genome-wide single nucleotide polymorphism arrays has demonstrated that somatically acquired regions of loss of heterozygosity without changes in copy number frequently occur in many types of cancer. Until recently, the ubiquity of this type of chromosomal defect had gone unrecognized because it cannot be detected by routine cytogenetic technologies. Random and recurrent patterns of copy-neutral loss of heterozygosity, also referred to as uniparental disomy, can be found in specific cancer types and probably contribute to clonal outgrowth owing to various mechanisms. In this review we explore the types, topography, genesis, pathophysiological consequences, and clinical implications of uniparental disomy. Clin Cancer Res; 17(12); 3913–23. ©2011 AACR.
T Cells in Tumors and Blood Predict Outcome in Follicular Lymphoma Treated with Rituximab
Authors: Wahlin Björn Engelbrekt , Sundström Christer , Holte Harald , Hagberg Hans , Erlanson Martin , Nilsson-Ehle Herman , Lindén Ola , Nordström Marie , Østenstad Bjørn , Geisler Christian H. , Brown Peter de Nully , Lehtinen Tuula , Maisenhölder Martin , Tierens Anne M. , Sander Birgitta , Christensson Birger , Kimby Eva 
Published: April 2011

AbstractPurpose: T cells influence outcome in follicular lymphoma, but their contributions seem to be modified by therapy. Their impact in patients receiving rituximab without chemotherapy is unknown.Experimental Design: Using flow cytometry, we evaluated the T cells in tumors and/or blood in a total of 250 follicular lymphoma patients included in two Nordic Lymphoma Group randomized trials that compared single rituximab with IFN-α2a–rituximab combinations.Results: In univariate analysis, higher levels of CD3+, CD4+, and CD8+ T cells in both tumors and blood correlated with superior treatment responses, and in multivariate analysis, tumor-CD3+ (P = 0.011) and blood-CD4+ (P = 0.029) cells were independent. CD4+ cells were favorable regardless of treatment arm, but CD8+ cells were favorable only in patients treated with single rituximab, because IFN-α2a improved responses especially in patients with low CD8+ cell levels. Higher levels of blood-CD3+ (P = 0.003) and blood-CD4+ (P = 0.046) cells predicted longer overall survival, and higher levels of blood-CD8+ cells longer times to next treatment (P = 0.046).Conclusions: We conclude that therapeutic effects of rituximab are augmented by tumor-associated T cells for rapid responses and by systemic T cells for sustained responses. CD4+ and CD8+ cells are both favorable in patients treated with rituximab. IFN-α2a abrogates the negative impact of few CD8+ cells. Clin Cancer Res; 17(12); 4136–44. ©2011 AACR.
Effective Melanoma Immunotherapy with Interleukin-2 Delivered by a Novel Polymeric Nanoparticle
Authors: Yao Hong , Ng Samuel S. , Huo Long-Fei , Chow Billy K. C. , Shen Zan , Yang Min , Sze Johnny , Ko Otis , Li Ming , Yue Alexander , Lu Li-Wei , Bian Xiu-Wu , Kung Hsiang-Fu , Lin Marie C. 
Published: April 2011

AbstractInterleukin-2 (IL-2) has been shown to possess antitumor activity in numerous preclinical and clinical studies. However, the short half-life of recombinant IL-2 protein in serum requires repeated high-dose injections, resulting in severe side effects. Although adenovirus-mediated IL-2 gene therapy has shown antitumor efficacy, the host antibody response to adenoviral particles and potential biosafety concerns still obstruct its clinical applications. Here we report a novel nanopolymer for IL-2 delivery, consisting of low molecular weight polyethylenimine (600Da) linked by β-cyclodextrin and conjugated with folate (named H1). H1 was mixed with IL-2 plasmid to form H1/pIL-2 polyplexes of around 100 nm in diameter. Peritumoral injection of these polyplexes suppressed the tumor growth and prolonged the survival of C57/BL6 mice bearing B16–F1 melanoma grafts. Importantly, the antitumor effects of H1/pIL-2 (50 μg DNA) were similar to those of recombinant adenoviruses expressing IL-2 (rAdv-IL-2; 2 × 108 pfu). Furthermore, we showed that H1/pIL-2 stimulated the activation and proliferation of CD8+, CD4+ T cell, and natural killer cells in peripheral blood and increased the infiltration of CD8+, CD4+ Tcells, and natural killer cells into the tumor environment. In conclusion, these results show that H1/pIL-2 is an effective and safe melanoma therapeutic with an efficacy comparable to that of rAdv-IL-2. This treatment represents an alternative gene therapy strategy for melanoma. Mol Cancer Ther; 10(6); 1082–92. ©2011 AACR.
Cancer Cells Cyclically Lose and Regain Drug-Resistant Highly Tumorigenic Features Characteristic of a Cancer Stem-like Phenotype
Authors: He Kaijie , Xu Tong , Goldkorn Amir 
Published: April 2011

Abstract
Drug resistance and brisk tumor initiation have traditionally been viewed as preexisting phenotypes present in small subpopulations of neoplastic cells sometimes termed cancer stem cells. However, recent work in cancer cell lines has shown that drug-resistant tumor-initiating features can emerge de novo within fractionated subpopulations of cells initially lacking these phenotypes. In the present study, we asked whether such phenotypic plasticity exists broadly in unperturbed cancer cell lines and tumor xenografts growing spontaneously without interventions such as drug selection or fractionation into subpopulations used in prior studies. To address this question, we used side population (SP) analysis combined with fluorescence labeling to identify a drug-resistant highly tumorigenic subpopulation and to track and analyze its interaction with the larger phenotypically negative population over time. Remarkably, we observed that SP size fluctuated in a cyclical manner: first contracting via differentiation into the non-SP (NSP) and then reexpanding via simultaneous direct conversion of numerous NSP cells back to the SP phenotype both in culture and in tumor xenografts. These findings show for the first time that adaptive, cancer-promoting traits such as drug resistance and brisk tumor initiation arise not only as solitary events under selective pressures but also as highly orchestrated transitions occurring concurrently in large numbers of cells even without specifically induced drug selection, ectopic gene expression, or fractionation into subpopulations. This high level of coordinated phenotypic plasticity bears consideration when using cancer cell lines as experimental models and may have significant implications for therapeutic efforts targeting cancer stem cells, which are marked by a drug-resistant tumor-initiating phenotype. Mol Cancer Ther; 10(6); 938–48. ©2011 AACR.
The Power of Play: Innovations in Getting Active Summit 2011
Authors: Lieberman Debra A. , Chamberlin Barbara , Medina Ernie , Franklin Barry A. , Sanner Brigid McHugh , Vafiadis Dorothea K. 
Published: April 2011

Background—
To examine the influence active-play video gaming (also referred to as exergaming, exertainment, and active gaming) might have on improving health-related skills, enhancing self-esteem and self-efficacy, promoting social support, and ultimately motivating positive changes in health behaviors, the American Heart Association convened The Power of Play: Innovations in Getting Active Summit. The summit, as well as a follow-up science panel, was hosted by the American Heart Association and Nintendo of America.

Methods and Results—
The science panel discussed the current state of research on active-play video gaming and its potential to serve as a gateway experience that might motivate players to increase the amount and intensity of physical activity in their daily lives. The panel identified the need for continued research on the gateway concept and on other behavioral health outcomes that could result from active-play video games and considered how these games could potentially affect disparate populations.

Conclusions—
The summit represented an exciting first step in convening healthcare providers, behavioral researchers, and professionals from the active-play video game industry to discuss the potential health benefits of active-play video games. Research is needed to improve understanding of processes of behavior change with active games. Future games and technologies may be designed with the goal to optimize physical activity participation, increase energy expenditure, and effectively address the abilities and interests of diverse and targeted populations. The summit helped the participants gain an understanding of what is known, identified gaps in current research, and supported a dialogue for continued collaboration.