bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prolyl oligopeptidase induces angiogenesis both in vitro and in vivo in a novel regulatory manner
Authors: Myöhänen TT , Tenorio‐Laranga J , Jokinen B , Vázquez‐Sánchez R , Moreno‐Baylach MJ , García‐Horsman JA , Männistö PT 
Published: December 2010

BACKGROUND AND PURPOSE A serine protease, prolyl oligopeptidase (POP) has been reported to be involved in the release of the pro‐angiogenic tetrapeptide acetyl‐N‐Ser‐Asp‐Lys‐Pro (Ac‐SDKP) from its precursor, 43‐mer thymosin β4 (Tβ4). Recently, it was shown that both POP activity and the levels of Ac‐SDKP are increased in malignant tumours. The aim of this study was to clarify the release of Ac‐SDKP, and test if POP and a POP inhibitor, 4‐phenyl‐butanoyl‐L‐prolyl‐2(S)‐cyanopyrrolidine (KYP‐2047), can affect angiogenesis.EXPERIMENTAL APPROACH We used HPLC for bioanalytical and an enzyme immunoassay for pharmacological analysis. Angiogenesis of human umbilical vein endothelial cells was assessed in vitro using a ‘tube formation’ assay and in vivo using a Matrigel plug assay (BD Biosciences, San Jose, CA, USA) in adult male rats. Moreover, co‐localization of POP and blood vessels was studied.KEY RESULTS We showed the sequential hydrolysis of Tβ4: the first‐step hydrolysis by proteases to <30‐mer peptides is followed by an action of POP. Unexpectedly, POP inhibited the first hydrolysis step, revealing a novel regulation system. POP with Tβ4 significantly induced, while KYP‐2047 effectively prevented, angiogenesis in both models compared with Tβ4 addition itself. POP and endothelial cells were abundantly co‐localized in vivo.CONCLUSIONS AND IMPLICATIONS We have now revealed that POP is a second‐step enzyme in the release of Ac‐SDKP from Tβ4, and it has novel autoregulatory effect in the first step. Our results also advocate a role for Ac‐SDKP in angiogenesis, and suggest that POP has a pro‐angiogenic role via the release of Ac‐SDKP from its precursor Tβ4 and POP inhibitors can block this action.
The antipyretic effect of dipyrone is unrelated to inhibition of PGE2 synthesis in the hypothalamus
Authors: Malvar David do C , Soares Denis M , Fabrício Aline SC , Kanashiro Alexandre , Machado Renes R , Figueiredo Maria J , Rae Giles A , de Souza Glória EP 
Published: December 2010

BACKGROUND AND PURPOSE Bacterial lipopolysaccharide (LPS) induces fever through two parallel pathways; one, prostaglandin (PG)‐dependent and the other, PG‐independent and involving endothelin‐1 (ET‐1). For a better understanding of the mechanisms by which dipyrone exerts antipyresis, we have investigated its effects on fever and changes in PGE2 content in plasma, CSF and hypothalamus induced by either LPS or ET‐1.EXPERIMENTAL APPROACH Rats were given (i.p.) dipyrone (120 mg·kg−1) or indomethacin (2 mg·kg−1) 30 min before injection of LPS (5 µg·kg−1, i.v.) or ET‐1 (1 pmol, i.c.v.). Rectal temperature was measured by tele‐thermometry. PGE2 levels were determined in the plasma, CSF and hypothalamus by elisa.KEY RESULTS LPS or ET‐1 induced fever and increased CSF and hypothalamic PGE2 levels. Two hours after LPS, indomethacin reduced CSF and hypothalamic PGE2 but did not inhibit fever, while at 3 h it reduced all three parameters. Three hours after ET‐1, indomethacin inhibited the increase in CSF and hypothalamic PGE2 levels but did not affect fever. Dipyrone abolished both the fever and the increased CSF PGE2 levels induced by LPS or ET‐1 but did not affect the increased hypothalamic PGE2 levels. Dipyrone also reduced the increase in the venous plasma PGE2 concentration induced by LPS.CONCLUSIONS AND IMPLICATIONS These findings confirm that PGE2 does not play a relevant role in ET‐1‐induced fever. They also demonstrate for the first time that the antipyretic effect of dipyrone was not mechanistically linked to the inhibition of hypothalamic PGE2 synthesis.
The Legitimacy Challenges for New Modes of Governance: Trustworthy Responsiveness
Authors: Føllesdal Andreas 
Published: December 2010

AbstractTwo typical features of new modes of governance (NMG) are of particular concern: (1) the delegation of regulatory activities to independent regulatory authorities at the national and the European level; and (2) regulatory networks outside the legislative arenas, with both private and public actors. These features tend to make the NMG less democratically accountable. Yet some hold that NMG can confer legitimacy on the European Union, especially because they secure ‘output’ more effectively than democratic arrangements, even though they lack any ‘input’ from voters. This article challenges these normative claims: the alleged benefits of NMG may be less than often claimed, while democratic accountability measures are less of a challenge to effectiveness and credibility, properly conceived.
New Modes of Governance and Democratic Accountability
Authors: Héritier Adrienne , Lehmkuhl Dirk 
Published: December 2010

AbstractThis article raises the question of the link between new modes of governance and democratic accountability. Our definition of new modes of governance as modes refers to public policy-making that includes private actors and/or public policy-making by public actors that takes place outside legislative arenas, and which focuses on delimited sectoral or functional areas. We identify three different ways in which new modes of governance can be subjected to democratic control: parliamentary control, multi-stakeholder involvement and control through the public sphere and civil society at large. Building on a number of the illustrative insights from various empirical projects, we find that, in our cases at least, new modes of governance did not have a negative effect on existing patterns of democratic accountability. At the same time, neither multi-stakeholder policies nor the participation of civil society guarantee democratic accountability in the strict sense. We provide some evidence to the effect that, if institutionally linked to democratically elected governmental bodies – meaning, in this context, the European Parliament – it is more likely that negative externalities deriving from public policy-making in functionally segmented arenas of the European Union's multilevel polity will be dealt with in a more systematic way.
Effect of percutaneous transluminal angioplasty on tissue oxygenation in ischemic diabetic feet
Authors: Kim Hong‐Ryul , Han Seung‐Kyu , Rha Seung‐Woon , Kim Hyun‐Surk , Kim Woo‐Kyung 
Published: December 2010

ABSTRACTPercutaneous transluminal angioplasty (PTA) has been performed as an alternative to bypass surgery for improving tissue oxygenation in ischemic diabetic feet because the former is less invasive than the latter. The purpose of this study was to evaluate the effect of PTA on tissue oxygenation in ischemic diabetic feet. This study included 29 ischemic diabetic feet, as determined by a transcutaneous oxygen pressure (TcPO2)<30 mmHg. The PTA was carried out in 29 limbs. The PTA procedure was considered successful, acceptable, and failed when residual stenosis was<30%, between 30 and 50%, and>50%, respectively. For evaluation of tissue oxygenation, the foot TcPO2 was measured before PTA and weekly for 6 weeks after PTA. Immediately after PTA, 26 feet were evaluated as being successful and the remaining three as acceptable. Before PTA, the average foot TcPO2 was 12.7±8.9 mmHg. The TcPO2 values were increased to 43.6±24.1, 51.0±22.6, 58.3±23.0, 61.3±24.2, 59.0±22.2, and 53.8±21.0 mmHg 1, 2, 3, 4, 5, and 6 weeks after PTA, respectively (p<0.01). The PTA procedure significantly increases tissue oxygenation in ischemic diabetic feet. The maximal level of tissue oxygenation was measured on the fourth week following PTA.
Bioactive peptides derived from vascular endothelial cell extracellular matrices promote microvascular morphogenesis and wound healing in vitro
Authors: Demidova‐Rice Tatiana N. , Geevarghese Anita , Herman Ira M. 
Published: December 2010

ABSTRACTStudies in our laboratory indicate that collagenase from Clostridium histolyticum promotes endothelial cell and keratinocyte responses to injury in vitro and wound healing in vivo. We postulate that matrix degradation by Clostridial collagenase creates bioactive fragments that can stimulate cellular responses to injury and angiogenesis. To test this hypothesis, we performed limited digestion of defined capillary‐endothelial‐derived extracellular matrices using purified human or bacterial collagenases. Immunoprecipitation with antibodies recognizing collagens I, II, III, IV, and V, followed by mass spectrometry reveals the presence of unique fragments in bacterial, but not human‐enzyme‐digested matrix. Results show that there are several bioactive peptides liberated from Clostridial collagenase‐treated matrices, which facilitate endothelial responses to injury, and accelerate microvascular remodeling in vitro. Fragments of collagen IV, fibrillin‐1, tenascin X, and a novel peptide created by combining specific amino acids contained within fibrillin 1 and tenascin X each have profound proangiogenic properties. The peptides used at 10–100 nM increase rates of microvascular endothelial cell proliferation by up to 47% and in vitro angiogenesis by 200% when compared with serum‐stimulated controls. Current studies are aimed at revealing the molecular mechanisms regulating peptide‐induced wound healing while extending these in vitro observations using animal modeling.
Akt‐mediated mechanotransduction in murine fibroblasts during hypertrophic scar formation
Authors: Paterno Josemaria , Vial Ivan N. , Wong Victor W. , Rustad Kristine C. , Sorkin Michael , Shi Yubin , Bhatt Kirit A. , Thangarajah Hariharan , Glotzbach Jason P. , Gurtner Geoffrey C. 
Published: December 2010

ABSTRACTAlthough numerous factors are implicated in skin fibrosis, the exact pathophysiology of hypertrophic scarring remains unknown. We recently demonstrated that mechanical force initiates hypertrophic scar formation in a murine model, potentially enhancing cellular survival through Akt. Here, we specifically examined Akt‐mediated mechanotransduction in fibroblasts using both strain culture systems and our murine scar model. In vitro, static strain increased fibroblast motility, an effect blocked by wortmannin (a phosphoinositide‐3‐kinase/Akt inhibitor). We also demonstrated that high‐frequency cyclic strain was more effective at inducing Akt phosphorylation than low frequency or static strain. In vivo, Akt phosphorylation was induced by mechanical loading of dermal fibroblasts in both unwounded and wounded murine skin. Mechanically loaded scars also exhibited strong expression of α‐smooth muscle actin, a putative marker of pathologic scar formation. In vivo inhibition of Akt increased apoptosis but did not significantly abrogate hypertrophic scar development. These data suggest that although Akt signaling is activated in fibroblasts during mechanical loading of skin, this is not the critical pathway in hypertrophic scar formation. Future studies are needed to fully elucidate the critical mechanotransduction components and pathways which activate skin fibrosis.
Combination of stromal cell‐derived factor‐1 and collagen–glycosaminoglycan scaffold delays contraction and accelerates reepithelialization of dermal wounds in wild‐type mice
Authors: Sarkar Aparajita , Tatlidede Soner , Scherer Saja Sandra , Orgill Dennis P. , Berthiaume François 
Published: December 2010

ABSTRACTWhile dermal substitutes can mitigate scarring and wound contraction, a significant drawback of current dermal replacement technologies is the apparent delay in vascular ingrowth compared with conventional skin grafts. Herein, we examined the effect of the chemokine stromal cell‐derived factor‐1 (SDF‐1) on the performance of a porous collagen–glycosaminoglycan dermal analog in excisional wounds in mice. C57BL/6 mice with 1 cm × 1 cm dorsal full‐thickness wounds were covered with a collagen–glycosaminoglycan scaffold, followed by four daily topical applications of 1 μg SDF‐1 or phosphate‐buffered saline vehicle. Some animals were also pretreated with five daily doses of 300 mg/kg granulocyte colony‐stimulating factor. Animals treated with SDF‐1 and no granulocyte colony‐stimulating factor reepithelialized 36% faster than vehicle controls (16 vs. 25 days), and exhibited less wound contraction on postwounding day 18 (∼35% greater wound area) plus three‐fold longer neoepidermis formed than controls. Conversely, granulocyte colony‐stimulating factor promoted contraction and no epidermal regeneration. Early (postwounding Day 3) inflammatory cell infiltration in the SDF‐1‐treated group was 86% less, while the fraction of proliferating cells (positive Ki67 staining) was 32% more, when compared with controls. These results suggest that SDF‐1 simultaneously delays contraction and promotes reepithelialization and may improve the wound‐healing performance of skin substitutes.
A role for Notch signaling in corneal wound healing
Authors: Ma Aihua , Zhao Bojun , Boulton Mike , Albon Julie 
Published: December 2010

ABSTRACTTo identify the role of the Notch signaling pathway in corneal wound healing, rat corneas receiving either epithelial or stromal wounds were placed in organ culture for up to 3 and 14 days, respectively. Localization of Notch receptors—Notch1, Notch2, and their ligands—Delta1, Jagged1 was determined by immunofluorescence. Wounds were treated with a γ‐secretase inhibitor to suppress Notch signaling or recombinant Jagged1 to enhance Notch signaling and morphological changes in the epithelium and stroma were recorded. The expressions of markers of cell proliferation (Ki67) and epithelial differentiation (cytokeratin 3) were assessed by immunohistology. Notch1 and Notch2 were localized to suprabasal epithelial cells in normal corneas. During corneal wound healing, both Notch receptors were detected in suprabasal and superficial epithelial layers. Delta1 and Jagged1 were observed throughout all corneal epithelial cell layers and occasional keratocytes of the stroma in normal and wounded corneas. γ‐secretase inhibition of Notch resulted in increased epithelial cell layers, with recombinant Jagged1 activation of Notch leading to a reduction in epithelial cell layers during corneal wound healing. Correspondingly, the activation of Notch resulted in a decreased cytokeratin 3 expression in the corneal epithelium, with no effect on cellular expression of Ki67. Notch signaling pathway suppressed corneal epithelial differentiation during corneal wound healing, but had no effect on epithelial cell proliferation.
Storage characteristics of cord blood progenitor cells: report of a multicenter study by the cellular therapies team of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative
Authors: Pamphilon Derwood , Curnow Elinor , Belfield Helen , Reems Jo‐Anna , McMannis John , Lecchi Lucilla , Szczepiorkowski Zbigniew , McKenna David 
Published: December 2010

BACKGROUND: Most hematopoietic progenitor cell (HPC) products are infused or processed shortly after collection, but in some cases this may be delayed for up to 48 hours. A number of variables such as temperature and cell concentration are of critical importance for the integrity of HPCs during this time.STUDY DESIGN AND METHODS: We evaluated critical variables using cord blood HPC units that were divided equally and stored at 4°C versus room temperature (RT) for up to 96 hours. Total nucleated cell (TNC) and mononuclear cell (MNC) counts, viable CD34+ cell counts, and CD45+ cell viability as well as colony‐forming unit–granulocyte‐macrophage (CFU‐GM) present over time at each temperature were determined.RESULTS: Overall, the data indicate that with the exception of viable CD34+ cells, there was a significant decrease in each variable measured for 72 to 96 hours and, with the exception of viable CD34+ cells and CFU‐GM, the reductions were significantly greater in RT units than 4°C units. There was an increase in viable CD34+ count for units where TNC count was greater than 8.5 × 109/L, compared with units where TNC count was less than 8.5 × 109/L, that was different for each storage temperature.CONCLUSIONS: Cord blood HPC collections maintained at 4°C retained higher TNC counts, MNC counts, and CD45+ cell viability over a 72‐ to 96‐hour storage period.
Investigation of heparin‐related hypotensive adverse events during photopheresis: utility of a patient care database
Authors: McPherson Richard A. , Buckler Aileen G. , Sanford Kimberly W. , Roseff Susan D. 
Published: December 2010

BACKGROUND:Extracorporeal photopheresis (ECP) is a procedure in which leukocytes are harvested from a patient's whole blood, treated with a DNA binding dye and ultraviolet light to inactivate lymphocytes, and then returned into the patient's circulation. In January 2008, we observed moderately severe anaphylactoid reactions in eight of 16 patients undergoing ECP.CASE STUDY:Each affected individual exhibited hypotension of sudden onset, usually with tachycardia, during the return of heparin‐anticoagulated blood at the end of the first cycle of collection of leukocytes. A systematic investigation of possible contributing factors revealed that all reactions were associated with administration of a single new lot of heparin.RESULTS:Changing to a different manufacturer of heparin eliminated the occurrence of further such hypotensive reactions during ECP. Although the symptoms were initially attributed to vasovagal reactions or dehydration, their temporal association with exposure to a new lot of heparin suggested a procedure‐related phenomenon. Of particular note, was the finding that of the eight patients who had reactions at any time, six had initial exposures without reactions, suggesting a process of sensitization.CONCLUSION:This study demonstrated the value of a patient database listing lot numbers of all medications and components used in each routine ECP procedure for facilitating rapid determination of common patient exposures, making it easier to determine the cause of adverse events, in this case, a particular lot of heparin responsible for the hypotensive adverse events.
Expression Profiling of Cassava Storage Roots Reveals an Active Process of Glycolysis/GluconeogenesisF
Authors: Yang Jun , An Dong , Zhang Peng 
Published: December 2010

Abstract Mechanisms related to the development of cassava storage roots and starch accumulation remain largely unknown. To evaluate genome‐wide expression patterns during tuberization, a 60 mer oligonucleotide microarray representing 20 840 cassava genes was designed to identify differentially expressed transcripts in fibrous roots, developing storage roots and mature storage roots. Using a random variance model and the traditional twofold change method for statistical analysis, 912 and 3 386 upregulated and downregulated genes related to the three developmental phases were identified. Among 25 significantly changed pathways identified, glycolysis/gluconeogenesis was the most evident one. Rate‐limiting enzymes were identified from each individual pathway, for example, enolase, L‐lactate dehydrogenase and aldehyde dehydrogenase for glycolysis/gluconeogenesis, and ADP‐glucose pyrophosphorylase, starch branching enzyme and glucan phosphorylase for sucrose and starch metabolism. This study revealed that dynamic changes in at least 16% of the total transcripts, including transcription factors, oxidoreductases/transferases/hydrolases, hormone‐related genes, and effectors of homeostasis. The reliability of these differentially expressed genes was verified by quantitative real‐time reverse transcription‐polymerase chain reaction. These studies should facilitate our understanding of the storage root formation and cassava improvement.
γ-rays and the far-infrared–radio continuum correlation reveal a powerful Galactic Centre wind
Authors: Crocker R. M. , Jones D. I. , Aharonian F. , Law C. J. , Melia F. , Ott J. 
Published: December 2010

Abstract
We consider the thermal and non-thermal emission from the inner 200 pc of the Galaxy. The radiation from this almost starburst-like region is ultimately driven dominantly by ongoing massive star formation. We show that this region's radio continuum (RC) emission is in relative deficit with respect to the expectation afforded by the far-infrared–radio continuum correlation (FRC). Likewise we show that the region's γ-ray emission falls short of that expected given its star formation and resultant supernova rates. These facts are compellingly explained by positing that a powerful (400–1200 km s−1) wind is launched from the region. This wind probably plays a number of important roles including advecting positrons into the Galactic bulge thus explaining the observed ∼kpc extension of the 511 keV positron annihilation signal around the GC. We also show that the large-scale GC magnetic field falls in the range ∼100–300 μG and that – in the time they remain in the region – GC cosmic rays do not penetrate into the region's densest molecular material.
Tails of the unexpected: the interaction of an isothermal shell with a cloud
Authors: Pittard J. M. 
Published: December 2010

Abstract
A new mechanism for the formation of cometary tails behind dense clouds or globules is discussed. Numerical hydrodynamical models show that when a dense shell of swept-up matter overruns a cloud, material in the shell is focused behind the cloud to form a tail. This mode of tail formation is completely distinct from other methods, which involve either the removal of material from the cloud or shadowing from a strong, nearby source of ionization. This mechanism is relevant to the cometary tails seen in planetary nebulae and to the interaction of superbubble shells with dense clouds.
Standing at the Crossroads – the Future of a Strong Common Agricultural Policy is at Stake  A la croisée des chemins – l’avenir d’une politique agricole commune forte est en jeu  Am Scheideweg – die Zukunft einer starken Gemeinsamen Agrarpolitik steht auf dem Spiel
Authors: Fazekas Sándor 
Published: December 2010

SummaryStanding at the Crossroads – the Future of a Strong Common Agricultural Policy is at StakeThe issues and targets in the European Union’s agenda are largely in line with Hungarian objectives; job creation for example is one of the main targets of the Europe 2020 strategy and also of the Hungarian Government. Hungary’s development and competitiveness are linked to the internal development and global competitiveness of the European Union; and so our primary objective is to strengthen the integration process and to obtain a strong Common Agricultural Policy. The CAP has reached the highest level of integration among EU policies and its original objectives have been reinforced by the Lisbon Treaty. Europe needs a strong and common agricultural policy beyond 2013; the main task of agriculture will be to ensure the security of food supplies. The future success of the CAP requires appropriate financial support to secure future targets. Rural development has already become an integral part of the CAP structure; but rural areas will not be viable without an evolving agriculture. Without the provision of a proper level of income subsidies many farms would be forced to stop production. CAP adjustments should promote the catching up of new Member States and eliminate the current system of direct subsidies that disadvantage the new members.