bluuebunny/crossref_metadata_2025_split huggingface dataset:
SK-216, an Inhibitor of Plasminogen Activator Inhibitor-1, Limits Tumor Progression and Angiogenesis
Authors: Masuda Takeshi , Hattori Noboru , Senoo Tadashi , Akita Shin , Ishikawa Nobuhisa , Fujitaka Kazunori , Haruta Yoshinori , Murai Hiroshi , Kohno Nobuoki 
Published: August 2013

AbstractPlasminogen activator inhibitor-1 (PAI-1), which can be produced by host and tumor cells in the tumor microenvironment, is intimately involved in tumor progression. In the present study, to pursue the possibility that PAI-1 could be a therapeutic target in the management of malignancy, SK-216, a specific PAI-1 inhibitor, was orally administered to wild-type mice that were subcutaneously implanted or intravenously injected with either PAI-1–secreting Lewis lung carcinoma (LLC) or PAI-1–nonsecreting B16 melanoma cells. The systemic administration of SK-216 was found to reduce the size of subcutaneous tumors and the extent of metastases, regardless of PAI-1 secretion levels from the tumor cells. SK-216 also reduced the extent of angiogenesis in the tumors and inhibited VEGF-induced migration and tube formation by human umbilical vein endothelial cells in vitro. Then, to determine whether host or tumor PAI-1 was more crucial in tumor progression and angiogenesis, PAI-1–deficient or wild-type mice were subcutaneously implanted or intravenously injected with LLC or PAI-1 knockdown LLC cells. Tumor progression was shown to be controlled by the presence of host PAI-1 and not affected by the PAI-1 levels in the tumors. Similarly, host PAI-1 played a more crucial role in tumor angiogenesis than did tumor PAI-1. These observations suggest that regardless of the PAI-1 levels in the tumor, the systemic administration of SK-216 exerts an antitumor effect through its interaction with host PAI-1. This antitumor effect might be mediated by the antiangiogenic properties of SK-216. Mol Cancer Ther; 12(11); 2378–88. ©2013 AACR.
Gene Expression Analyses of Mouse Aortic Endothelium in Response to Atherogenic Stimuli
Authors: Erbilgin Ayca , Siemers Nathan , Kayne Paul , Yang Wen-pin , Berliner Judith , Lusis Aldons J. 
Published: August 2013

Objective—
Endothelial cells are central to the initiation of atherosclerosis, yet there has been limited success in studying their gene expression in the mouse aorta. To address this, we developed a method for determining the global transcriptional changes that occur in the mouse endothelium in response to atherogenic conditions and applied it to investigate inflammatory stimuli.

Approach and Results—

We characterized a method for the isolation of endothelial cell RNA with high purity directly from mouse aortas and adapted this method to allow for the treatment of aortas ex vivo before RNA collection. Expression array analysis was performed on endothelial cell RNA isolated from control and hyperlipidemic prelesion mouse aortas, and 797 differentially expressed genes were identified. We also examined the effect of additional atherogenic conditions on endothelial gene expression, including ex vivo treatment with inflammatory stimuli, acute hyperlipidemia, and age. Of the 14 most highly differentially expressed genes in endothelium from prelesion aortas, 8 were also perturbed significantly by ≥1 atherogenic conditions:
2610019E17Rik, Abca1, H2-Ab1, H2-D1, Pf4, Ppbp, Pvrl2
, and
Tnnt2
.

Conclusions—
We demonstrated that RNA can be isolated from mouse aortic endothelial cells after in vivo and ex vivo treatments of the murine vessel wall. We applied these methods to identify a group of genes, many of which have not been described previously as having a direct role in atherosclerosis, that were highly regulated by atherogenic stimuli and may play a role in early atherogenesis.
Low Glomerular Filtration Rate, Recurrent Stroke Risk, and Effect of Renin–Angiotensin System Modulation
Authors: Ovbiagele Bruce , Bath Philip M. , Cotton Daniel , Sha Nanshi , Diener Hans-Christoph 
Published: August 2013

Background and Purpose—
To investigate the association of low estimated glomerular filtration rate (eGFR) <60 mL/min with recurrent stroke risk and to evaluate whether add-on renin–angiotensin system modulator therapy is associated with lower recurrent stroke risk in patients with low eGFR.

Methods—
We analyzed the database of a multicenter trial involving 18 666 patients with recent ischemic stroke followed for 2.5 years. Primary outcome was time to first recurrent stroke. Independent associations of low eGFR with outcome in the entire cohort and add-on telmisartan treatment with outcome among those with low eGFR were evaluated.

Results—
Low eGFR was observed in 3630 (20.1%) patients. Patients with low eGFR were older, more likely women, with a known history of hypertension. In unadjusted analyses, patients with low eGFR were more likely to experience a recurrent stroke (hazard ratio, 1.34; 95% confidence interval, 1.20–1.49). After adjusting for confounders, low eGFR was still associated with recurrent stroke but to a lesser extent (hazard ratio, 1.16; 95% confidence interval, 1.04–1.31). Telmisartan treatment among patients with low eGFR was not independently associated with recurrent stroke (hazard ratio, 1.08; 95% confidence interval, 0.89–1.31).

Conclusions—
Low eGFR is independently associated with a higher risk of recurrent stroke, but short-term add-on telmisartan therapy does not seem to mitigate this risk.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00153062.
World Politics by Other Means? London, City Diplomacy and the Olympics
Authors: Acuto Michele 
Published: August 2013

Summary
Drawing on the case of the Olympics, and in particular on the role of London in securing, planning and administering the 2012 Summer Games, this article investigates how cities participate in world politics beyond the traditional avenues of the international system. Tracing how the planning of a sporting mega-event has been woven into London’s international role as a global ‘green’ leader, the article seeks to shed some light on the diplomatic role of cities, as well as on how sport has been used in relation to city diplomacy and urban governance. The Olympics offer a unique window on the multi-scalar reach of these subnational authorities, allowing for substantial public diplomacy initiatives. Major cities such as London, as the article argues, can exert a pervasive diplomatic influence, and planning for sporting events can extend their capacity to link ‘city diplomacy’ with tangible impacts on everyday lives.
An Objective Satellite-Based Tropical Cyclone Size Climatology
Authors: Knaff John A. , Longmore Scott P. , Molenar Debra A. 
Published: August 2013

AbstractStorm-centered infrared (IR) imagery of tropical cyclones (TCs) is related to the 850-hPa mean tangential wind at a radius of 500 km (V500) calculated from 6-hourly global numerical analyses for North Atlantic and eastern North Pacific TCs for 1995–2011. V500 estimates are scaled using the climatological vortex decay rate beyond 500 km to estimate the radius of 5 kt (1 kt = 0.514 m s−1) winds (R5) or TC size. A much larger historical record of TC-centered IR imagery (1978–2011) is then used to estimate TC sizes and form a global TC size climatology. The basin-specific distributions of TC size reveal that, among other things, the eastern North Pacific TC basins have the smallest while western North Pacific have the largest TC size distributions. The life cycle of TC sizes with respect to maximum intensity shows that TC growth characteristics are different among the individual TC basins, with the North Atlantic composites showing continued growth after maximum intensity. Small TCs are generally located at lower latitudes, westward steering, and preferred in seasons when environmental low-level vorticity is suppressed. Large TCs are generally located at higher latitudes, poleward steering, and preferred in enhanced low-level vorticity environments. Postmaximum intensity growth of TCs occurs in regions associated with enhanced baroclinicity and TC recurvature, while those that do not grow much are associated with west movement, erratic storm tracks, and landfall at or near the time of maximum intensity. With respect to climate change, no significant long-term trends are found in the dataset of TC size.
The effects of statins on the mevalonic acid pathway in recombinant yeast strains expressing human HMG-CoA reductase
Authors: Maciejak Agata , Leszczynska Agata , Warchol Ilona , Gora Monika , Kaminska Joanna , Plochocka Danuta , Wysocka-Kapcinska Monika , Tulacz Dorota , Siedlecka Joanna , Swiezewska Ewa , Sojka Maciej , Danikiewicz Witold , Odolczyk Norbert , Szkopinska Anna , Sygitowicz Grazyna , Burzynska Beata 
Published: August 2013

Abstract

Background
The yeast Saccharomyces cerevisiae can be a useful model for studying cellular mechanisms related to sterol synthesis in humans due to the high similarity of the mevalonate pathway between these organisms. This metabolic pathway plays a key role in multiple cellular processes by synthesizing sterol and nonsterol isoprenoids. Statins are well-known inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the key enzyme of the cholesterol synthesis pathway. However, the effects of statins extend beyond their cholesterol-lowering action, since inhibition of HMGR decreases the synthesis of all products downstream in the mevalonate pathway. Using transgenic yeast expressing human HMGR or either yeast HMGR isoenzyme we studied the effects of simvastatin, atorvastatin, fluvastatin and rosuvastatin on the cell metabolism.

Results
Statins decreased sterol pools, prominently reducing sterol precursors content while only moderately lowering ergosterol level. Expression of genes encoding enzymes involved in sterol biosynthesis was induced, while genes from nonsterol isoprenoid pathways, such as coenzyme Q and dolichol biosynthesis or protein prenylation, were diversely affected by statin treatment. Statins increased the level of human HMGR protein substantially and only slightly affected the levels of Rer2 and Coq3 proteins involved in non-sterol isoprenoid biosynthesis.

Conclusion
Statins influence the sterol pool, gene expression and protein levels of enzymes from the sterol and nonsterol isoprenoid biosynthesis branches and this effect depends on the type of statin administered. Our model system is a cheap and convenient tool for characterizing individual statins or screening for novel ones, and could also be helpful in individualized selection of the most efficient HMGR inhibitors leading to the best response and minimizing serious side effects.
Improvement of the efficacy of dihydroartemisinin with atorvastatin in an experimental cerebral malaria murine model
Authors: Dormoi Jérôme , Briolant Sébastien , Pascual Aurélie , Desgrouas Camille , Travaillé Christelle , Pradines Bruno 
Published: August 2013

Abstract

Background
The medical care of malaria is a clinical emergency because it may develop into severe malaria, which has a high risk of complications and death. One of the major complications of Plasmodium falciparum infections is cerebral malaria (CM), which is responsible for at least 175,000 deaths worldwide each year and has long-term neurological sequelae. Moreover, treatment for CM is only partially effective. Statins are now known to have anti-inflammatory action, to attenuate sepsis and to have neuroprotective effects. In vitro, atorvastatin (AVA) has an anti-malarial activity and has improved the activity of quinine (QN), mefloquine (MQ), and dihydroartemisinin (DHA).

Objectives
This study had two objectives. First, the ability of AVA to enhance DHA efficacy by improving the survival rate for CM and also decreasing signs of CM was evaluated in a murine model of experimental cerebral malaria (ECM), which was designed in C57BL6/N mice. Second, the inflammatory biomarkers were assessed at D6 and D10 in mice treated by DHA and in untreated mice in which clinical signs of CM appear rapidly and death occurs before D12. Both experiments were designed with seven days of treatment with 40 mg/kg AVA combined with five days of 3 mg/kg DHA administered intraperitoneally.

Results
AVA in combination with DHA in a therapeutic scheme leads to a significant delay in mouse death, and it has an effect on the onset of CM symptoms and on the level of parasitaemia. Evaluation of the biomarkers highlights the significant difference between treated and control mice for five cytokines and chemokines (Eotaxin-CCL11, IL-13, LIX-CXCL5, MIP1b-CCL4 and MIP2) that are known to have a role in chemotaxis.

Conclusions
The combination of DHA and AVA seems to be effective as a therapeutic scheme for improving mouse survival but less effective for cytokine modulation, which is associated with protection against CM. These results call for clinical trials of AVA as an adjuvant with anti-malarial therapy, especially with artemisinin-based combination therapy, in CM treatment or prevention.
Reduction in thermal conductivity of Bi thin films with high-density ordered nanoscopic pores
Authors: Kim Gil-Sung , Lee Mi-Ri , Lee Seung-Yong , Hyung Jung-Hwan , Park No-Won , Lee Eun Sun , Lee Sang-Kwon 
Published: August 2013

Abstract
We prepared two-dimensional Bi thin films with high-density ordered nanoscopic pores by e-beam evaporation of Bi metal. For this structure, we used polystyrene beads ranging from 200 to 750 nm in diameter as an etch mask. The typical hole and neck sizes of the Bi thin films with approximately 50 nm in thickness on SiO2/Si substrates were in the range of 135 to 490 nm and 65 to 260 nm, respectively. By measuring the thermal characteristics through a 3ω technique, we found that the thermal conductivities of nanoporous Bi thin films are greatly suppressed compared with those of corresponding bulk materials. With a decrease in pore size to approximately 135 nm, the thermal conductivity decreased significantly to approximately 0.46 W/m·K at 300 K.
Design and descriptive epidemiology of the Infectious Diseases of East African Livestock (IDEAL) project, a longitudinal calf cohort study in western Kenya
Authors: de Clare Bronsvoort Barend Mark , Thumbi Samuel Mwangi , Poole Elizabeth Jane , Kiara Henry , Auguet Olga Tosas , Handel Ian Graham , Jennings Amy , Conradie Ilana , Mbole-Kariuki Mary Ndila , Toye Philip G , Hanotte Olivier , Coetzer JAW , Woolhouse Mark EJ 
Published: August 2013

Abstract

Background
There is a widely recognised lack of baseline epidemiological data on the dynamics and impacts of infectious cattle diseases in east Africa. The Infectious Diseases of East African Livestock (IDEAL) project is an epidemiological study of cattle health in western Kenya with the aim of providing baseline epidemiological data, investigating the impact of different infections on key responses such as growth, mortality and morbidity, the additive and/or multiplicative effects of co-infections, and the influence of management and genetic factors.
A longitudinal cohort study of newborn calves was conducted in western Kenya between 2007-2009. Calves were randomly selected from all those reported in a 2 stage clustered sampling strategy. Calves were recruited between 3 and 7 days old. A team of veterinarians and animal health assistants carried out 5-weekly, clinical and postmortem visits. Blood and tissue samples were collected in association with all visits and screened using a range of laboratory based diagnostic methods for over 100 different pathogens or infectious exposures.

Results
The study followed the 548 calves over the first 51 weeks of life or until death and when they were reported clinically ill. The cohort experienced a high all cause mortality rate of 16% with at least 13% of these due to infectious diseases. Only 307 (6%) of routine visits were classified as clinical episodes, with a further 216 reported by farmers. 54% of calves reached one year without a reported clinical episode. Mortality was mainly to east coast fever, haemonchosis, and heartwater. Over 50 pathogens were detected in this population with exposure to a further 6 viruses and bacteria.

Conclusion
The IDEAL study has demonstrated that it is possible to mount population based longitudinal animal studies. The results quantify for the first time in an animal population the high diversity of pathogens a population may have to deal with and the levels of co-infections with key pathogens such as Theileria parva. This study highlights the need to develop new systems based approaches to study pathogens in their natural settings to understand the impacts of co-infections on clinical outcomes and to develop new evidence based interventions that are relevant.
Asarum pubitessellatum, sp. nov. (sect. Heterotropa, Aristolochiaceae) from Taiwan based on morphological and palynological evidence
Authors: Lu Chang-Tse , Chiou Wen-Liang , Wang Jenn-Che 
Published: August 2013

AbstractBackgroundRecently, we discovered an unknownAsarumfrom Taiwan which is closely related toA. crassisepalumS.F. Huang, T.H. Hsieh and T.C. Huang andA. taipingshanianumS.F. Huang, T.H. Hsieh and T.C. Huang by sharing a thick leaf blade, spreading perianth-lobes and a conical to cylindrical perianth-tube. We compared it with other related species and identified this plant as a new species.ResultsThis new species differs distinctly from the above two related species by having larger plant body, shortened rhizomes and an inner surface of the perianth-tube that is covered with numerous simple trichomes (vs. glandular trichomes). The pollen tectum in this new species is perforate, which differs from the incomplete reticulate with small supratectate granules inA. crassisepalumand the compact rugulate with small supratectate granules inA. taipingshanianum. Furthermore, these three species are geographically separated from one another.ConclusionsAsarum pubitessellatumC.T. Lu & J.C. Wang, a new species is described and illustrated. The trichomes on the inner surface of the perianth-tube and pollen micromorphology were the valuable characters in the low-level classification ofHeterotropaspecies in Taiwan.
Inhaled corticosteroid treatment for 6 months was not sufficient to normalize phagocytosis in asthmatic children
Authors: da Silva‐Martins Carmen Lívia Faria , Couto Shirley Claudino , Muniz‐Junqueira Maria Imaculada 
Published: August 2013

AbstractBackgroundCorticosteroids are the first‐line therapy for asthma; however, the effect of corticosteroids on the innate immune system remains unclear. This study's objective was to evaluate the effect of inhaled corticosteroid therapy (ICT) on phagocytic functions.MethodsTo evaluate the impact of ICT, the phagocytosis of Saccharomyces cerevisiae by blood monocytes and neutrophils and the production of superoxide anions were assessed before and after three and six months of ICT treatment in 58 children with persistent asthma and 21 healthy controls.ResultsWe showed that the phagocytic capacity of monocytes and neutrophils that occurred via pattern recognition receptors or was mediated by complement and immunoglobulin receptors in asthmatic children before treatment was significantly lower than in healthy controls (p<0.05, Mann–Whitney test) and was not influenced by the severity of the clinical form of the disease. Although there was clinical improvement with treatment, ICT for 6 months was not sufficient to normalize phagocytosis by the phagocytes. Superoxide anion production was also decreased in the asthmatic children before treatment, and ICT normalized the O‐ production only for children with mild persistent asthma when assessed at baseline but caused this function to decrease after stimulation (p<0.05, Kruskal‐Wallis test).ConclusionsOur data suggest that an immunodeficiency in phagocytes remained even after treatment. However, this immunodeficiency does not appear to correspond with the clinical evolution of asthma because an improvement in clinical parameters occurred.
Cellular stress response and innate immune signaling: integrating pathways in host defense and inflammation
Authors: Muralidharan Sujatha , Mandrekar Pranoti 
Published: August 2013

ABSTRACTExtensive research in the past decade has identified innate immune recognition receptors and intracellular signaling pathways that culminate in inflammatory responses. Besides its role in cytoprotection, the importance of cell stress in inflammation and host defense against pathogens is emerging. Recent studies have shown that proteins in cellular stress responses, including the heat shock response, ER stress response, and DNA damage response, interact with and regulate signaling intermediates involved in the activation of innate and adaptive immune responses. The effect of such regulation by cell stress proteins may dictate the inflammatory profile of the immune response during infection and disease. In this review, we describe the regulation of innate immune cell activation by cell stress pathways, present detailed descriptions of the types of stress response proteins and their crosstalk with immune signaling intermediates that are essential in host defense, and illustrate the relevance of these interactions in diseases characteristic of aberrant immune responses, such as chronic inflammatory diseases, autoimmune disorders, and cancer. Understanding the crosstalk between cellular stress proteins and immune signaling may have translational implications for designing more effective regimens to treat immune disorders.
Bile acids PKA-dependently induce a switch of the IL-10/IL-12 ratio and reduce proinflammatory capability of human macrophages
Authors: Haselow Katrin , Bode Johannes G , Wammers Marianne , Ehlting Christian , Keitel Verena , Kleinebrecht Laura , Schupp Anna-Kathrin , Häussinger Dieter , Graf Dirk 
Published: August 2013

ABSTRACTThat cholestatic conditions are accompanied by an enhanced susceptibility to bacterial infection in human and animal models is a known phenomenon. This correlates with the observation that bile acids have suppressive effects on cells of innate and adaptive immunity. The present study provides evidence that in human macrophages, bile acids inhibit the LPS-induced expression of proinflammatory cytokines without affecting the expression of the anti-inflammatory cytokine IL-10. This results in a macrophage phenotype that is characterized by an increased IL-10/IL-12 ratio. Correspondingly, bile acids suppress basal phagocytic activity of human macrophages. These effects of bile acids can be mimicked by cAMP, which is presumably induced TGR5-dependently. The data provided further suggest that in primary human macrophages, modulation of the macrophage response toward LPS by bile acids involves activation of CREB, disturbed nuclear translocation of NF-κB, and PKA-dependent enhancement of LPS-induced cFos expression. The increase in cFos expression is paralleled by an enhanced formation of a protein complex comprising cFos and the p65 subunit of NF-κB. In summary, the data provided suggest that in human macrophages, bile acids induce an anti-inflammatory phenotype characterized by an increased IL-10/IL-12 ratio via activation of PKA and thereby, prevent their activation as classically activated macrophages. This bile acid-induced modulation of macrophage function may also be responsible for the experimentally and clinically observed anti-inflammatory and immunosuppressive effects of bile acids.