bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fetal asphyctic preconditioning modulates the acute cytokine response thereby protecting against perinatal asphyxia in neonatal rats
Authors: Vlassaks Evi , Strackx Eveline , Vles Johan SH , Nikiforou Maria , Martinez-Martinez Pilar , Kramer Boris W , Gavilanes Antonio WD 
Published: January 2013

Abstract

Background
Perinatal asphyxia (PA) is a major cause of brain damage and neurodevelopmental impairment in infants. Recent investigations have shown that experimental sublethal fetal asphyxia (FA preconditioning) protects against a subsequent more severe asphyctic insult at birth. The molecular mechanisms of this protection have, however, not been elucidated. Evidence implicates that inflammatory cytokines play a protective role in the induction of ischemic tolerance in the adult brain. Accordingly, we hypothesize that FA preconditioning leads to changes in the fetal cytokine response, thereby protecting the newborn against a subsequent asphyctic insult.

Methods
In rats, FA preconditioning was induced at embryonic day 17 by clamping the uterine vasculature for 30 min. At term birth, global PA was induced by placing the uterine horns, containing the pups, in a saline bath for 19 min. We assessed, at different time points after FA and PA, mRNA and protein expression of several cytokines and related receptor mRNA levels in total hemispheres of fetal and neonatal brains. Additionally, we measured pSTAT3/STAT3 levels to investigate cellular responses to these cytokines.

Results
Prenatally, FA induced acute downregulation in IL-1β, TNF-α and IL-10 mRNA levels. At 96 h post FA, IL-6 mRNA and IL-10 protein expression were increased in FA brains compared with controls. Two hours after birth, all proinflammatory cytokines and pSTAT3/STAT3 levels decreased in pups that experienced FA and/or PA. Interestingly, IL-10 and IL-6 mRNA levels increased after PA. When pups were FA preconditioned, however, IL-10 and IL-6 mRNA levels were comparable to those in controls.

Conclusions
FA leads to prenatal changes in the neuroinflammatory response. This modulation of the cytokine response probably results in the protective inflammatory phenotype seen when combining FA and PA and may have significant implications for preventing post-asphyctic perinatal encephalopathy.
High number of CD56bright NK-cells and persistently low CD4+ T-cells in a hemophiliac HIV/HCV co-infected patient without opportunistic infections
Authors: Fregni Giulia , Maresca Anaenza Freire , Jalbert Valérie , Caignard Anne , Scott-Algara Daniel , Cramer Elisabeth Bordé , Rouveix Elisabeth , Béné Marie C , Capron Claude 
Published: January 2013

AbstractBackgroundBoth the human immunodeficiency virus (HIV) and hepatitis C virus (HCV), either alone or as coinfections, persist in their hosts by destroying and/or escaping immune defenses, with high morbidity as consequence. In some cases, however, a balance between infection and immunity is reached, leading to prolonged asymptomatic periods. We report a case of such an indolent co-infection, which could be explained by the development of a peculiar subset of Natural Killer (NK) cells.ResultsPersistently high peripheral levels of CD56+NK cells were observed in a peculiar hemophiliac HIV/HCV co-infected patient with low CD4 counts, almost undetectable HIV viral load and no opportunistic infections. Thorough analysis of NK-subsets allowed to identify a marked increase in the CD56bright/dimcell ratio and low numbers of CD16+/CD56-cells. These cells have high levels of natural cytotoxicity receptors but low NCR2 and CD69, and lack both CD57 and CD25 expression. The degranulation potential of NK-cells which correlates with target cytolysis was atypically mainly performed by CD56brightNK-cells, whereas no production of interferon γ (IFN-γ) was observed following NK activation by K562 cells.ConclusionsThese data suggest that the expansion and lytic capacity of the CD56brightNK subset may be involved in the protection of this « rare » HIV/HCV co-infected hemophiliac A patient from opportunistic infections and virus-related cancers despite very low CD4+cell counts.
Viral Encephalopathy and Retinopathy in groupers (Epinephelusspp.) in southern Italy: a threat for wild endangered species?
Authors: Vendramin Niccolò , Patarnello Pierpaolo , Toffan Anna , Panzarin Valentina , Cappellozza Elisabetta , Tedesco Perla , Terlizzi Antonio , Terregino Calogero , Cattoli Giovanni 
Published: January 2013

Abstract

Background
Betanodaviruses are the causative agents of Viral Encephalopathy and Retinopathy (VER). To date, more than 50 species have proved to be susceptible and among them, those found in genus Epinephelus are highly represented. Clinical disease outbreaks are generally characterized by typical nervous signs and significant mortalities mainly associated with aquaculture activities, although some concerns for the impact of this infection in wild fish have been raised. In this study, the authors present the first documented report describing an outbreak of VER in wild species in the Mediterranean basin.

Case presentation
In late summer - early winter 2011 (September-December), significant mortalities affecting wild Dusky grouper (Epinephelus marginatus), Golden grouper (Epinephelus costae) and European sea bass (Dicentrarchus labrax) were reported in the municipality of Santa Maria di Leuca (Northern Ionian Sea, Italy). The affected fish showed an abnormal swimming behavior and swollen abdomens. During this epizootic, five moribund fish showing clear neurological signs were captured and underwent laboratory investigations. Analytical results confirmed the diagnosis of VER in all the specimens. Genetic characterization classified all betanodavirus isolates as belonging to the RGNNV genotype, revealing a close genetic relationship with viral sequences obtained from diseased farmed fish reared in the same area in previous years.

Conclusion
The close relationship of the viral sequences between the isolates collected in wild affected fish and those isolated during clinical disease outbreaks in farmed fish in the same area in previous years suggests a persistent circulation of betanodaviruses and transmission between wild and farmed stocks. Further investigations are necessary to assess the risk of viral transmission between wild and farmed fish populations, particularly in marine protected areas where endangered species are present.
Experimental and quantum chemical studies of a novel synthetic prenylated chalcone
Authors: Espinoza-Hicks José C , Camacho-Dávila Alejandro A , Flores-Holguín Norma R , Nevárez-Moorillón Guadalupe V , Glossman-Mitnik Daniel , Rodríguez-Valdez Luz M 
Published: January 2013

AbstractBackgroundChalcones are ubiquitous natural compounds with a wide variety of reported biological activities, including antitumoral, antiviral and antimicrobial effects. Furthermore, chalcones are being studied for its potential use in organic electroluminescent devices; therefore the description of their spectroscopic properties is important to elucidate the structure of these molecules. One of the main techniques available for structure elucidation is the use of Nuclear Magnetic Resonance Spectroscopy (NMR). Accordingly, the prediction of the NMR spectra in this kind of molecules is necessary to gather information about the influence of substituents on their spectra.ResultsA novel substituted chalcone has been synthetized. In order to identify the functional groups present in the new synthesized compound and confirm its chemical structure, experimental and theoretical1H-NMR and13C-NMR spectra were analyzed. The theoretical molecular structure and NMR spectra were calculated at both the Hartree-Fock and Density Functional (meta: TPSS; hybrid: B3LYP and PBE1PBE; hybrid meta GGA: M05-2X and M06-2X) levels of theory in combination with a 6-311++G(d,p) basis set. The structural parameters showed that the best method for geometry optimization was DFT:M06-2X/6-311++G(d,p), whereas the calculated bond angles and bond distances match experimental values of similar chalcone derivatives. The NMR calculations were carried out using the Gauge-Independent Atomic Orbital (GIAO) formalism in a DFT:M06-2X/6-311++G(d,p) optimized geometry.ConclusionConsidering all HF and DFT methods with GIAO calculations, TPSS and PBE1PBE were the most accurate methods used for calculation of1H-NMR and13C-NMR chemical shifts, which was almost similar to the B3LYP functional, followed in order by HF, M05-2X and M06-2X methods. All calculations were done using the Gaussian 09 software package. Theoretical calculations can be used to predict and confirm the structure of substituted chalcones with good correlation with the experimental data.
Pharmacokinetics of combined gene therapy expressing constitutive human GM-CSF and hyperthermia-regulated human IL-12
Authors: Wei Fang , Wang Huiping , Zhang Jufeng , Chen Xiafang , Li Chuanyuan , Huang Qian 
Published: January 2013

Abstract

Background
An adenovirus that expresses both interleukin (IL)-12 and granulocyte-macrophage colony-stimulating-factor (GM-CSF) has been proven to be very effective in treating several tumors, but causes serious normal tissue toxicities.

Methods
In this study, a novel adenoviral vector was constructed by placing the human GM-CSF gene under the control of the CMV-IE promoter and human IL-12 gene under the control of heat shock protein 70B gene promoter. Both hGM-CSF and hIL-12 expressions in virus-infected tumor cells were analyzed in vitro and in vivo when underlying single or multiple rounds of hyperthermia.

Results
We observed constitutive high expression of human GM-CSF and heat-induced expression of human IL-12 after a single round of hyperthermia post viral infection. The heat-induced hIL-12 expression exhibited a pulse-like pattern with a peak at 24 hrs followed by a decline 48 hrs post heat stress. Repeated heat treatment was more effective in inducing hIL-12 expression than a one-time heat treatment. Interestedly, we also observed that constitutive expression of hGM-CSF could be stimulated by heat stress in tested tumor cells.

Conclusion
Our study provided a novel strategy for combined gene therapy that allows constitutive expression of a non-toxic gene such as GM-CSF and heat-induced expression of a toxic gene such as IL-12. In addition, our study also showed that hyperthermia can be used to trigger gene expression in temporal and special manner.
PRIMA-1 increases cisplatin sensitivity in chemoresistant ovarian cancer cells with p53 mutation: a requirement for Akt down-regulation
Authors: Kobayashi Noriko , Abedini Mohammadreza , Sakuragi Noriaki , Tsang Benjamin K 
Published: January 2013

Abstract

Background
Since ovarian cancer is associated with high frequency of p53 mutation, the availability of p 53 r eactivation and i nduction of m assive a poptosis (PRIMA-1) offers a possible new therapeutic strategy for overcoming this devastating disease. Although Akt activation is believed to be a determinant in chemoresistance in ovarian cancer, whether Akt plays a role in regulating the effectiveness of PRIMA-1 in sensitizing chemoresistant ovarian cancer cells with p53 mutation to cisplatin (CDDP), remains to be determined.

Methods
In the present studies, we examined the influence of Akt down-regulation following dominant-negative (DN-Akt) expression on the ability of PRIMA-1 (0–10 μM) to facilitate CDDP (0–10 μM)-induced apoptosis in p53-mutated chemoresistant ovarian cancer cells (A2780cp).

Results
Apoptosis rate was significantly higher at the combined treatment of low PRIMA-1 concentrations (0.156 - 0.938 μM) plus CDDP (10 μM) in the DN-Akt groups than control (p<0.001). Apoptosis in cells treated with PRIMA-1 (0.156 μM) and CDDP treatment (10 μM) was significantly suppressed by p53-siRNA. PRIMA-1 increased phospho-p53 (Ser15) content in Akt down-regulated cells treated with CDDP.

Conclusions
These results demonstrate that PRIMA-1 can sensitize chemoresistant ovarian cancer cells with p53 mutation to CDDP when Akt is down-regulated, and the action of PRIMA-1 is associated with p53 activation. Our findings raise the possibility that PRIMA-1 may be useful candidate for adjuvant therapy with CDDP in chemoresistant ovarian cancer with p53 mutation when Akt is down-regulated.
Functional expression of a proton-coupled organic cation (H+/OC) antiporter in human brain capillary endothelial cell line hCMEC/D3, a human blood–brain barrier model
Authors: Shimomura Keita , Okura Takashi , Kato Sayaka , Couraud Pierre-Olivier , Schermann Jean-Michel , Terasaki Tetsuya , Deguchi Yoshiharu 
Published: January 2013

Abstract

Background
Knowledge of the molecular basis and transport function of the human blood–brain barrier (BBB) is important for not only understanding human cerebral physiology, but also development of new central nervous system (CNS)-acting drugs. However, few studies have been done using human brain capillary endothelial cells, because human brain materials are difficult to obtain. The purpose of this study is to clarify the functional expression of a proton-coupled organic cation (H+/OC) antiporter in human brain capillary endothelial cell line hCMEC/D3, which has been recently developed as an in vitro human BBB model.

Methods
Diphenhydramine, [3H]pyrilamine and oxycodone were used as cationic drugs that proved to be H+/OC antiporter substrates. The in vitro uptake experiments by hCMEC/D3 cells were carried out under several conditions.

Results
Diphenhydramine and [3H]pyrilamine were both transported into hCMEC/D3 cells in a time- and concentration-dependent manner with Km values of 59 μM and 19 μM, respectively. Each inhibited uptake of the other in a competitive manner, suggesting that a common mechanism is involved in their transport. The diphenhydramine uptake was significantly inhibited by amantadine and quinidine, but not tetraethylammonium and 1-methyl-4-phenylpyridinium (substrates for well-known organic cation transporters). The uptake was inhibited by metabolic inhibitors, but was insensitive to extracellular sodium and membrane potential. Further, the uptake was increased by extracellular alkalization and intracellular acidification. These transport properties are completely consistent with those of previously characterized H+/OC antiporter in rat BBB.

Conclusions
The present results suggest that H+/OC antiporter is functionally expressed in hCMEC/D3 cells.
An assessment of the concentrations of pharmaceutical compounds in wastewater treatment plants on the island of Gran Canaria (Spain)
Authors: Guedes-Alonso Rayco , Afonso-Olivares Cristina , Montesdeoca-Esponda Sarah , Sosa-Ferrera Zoraida , Santana-Rodríguez José Juan 
Published: January 2013

Abstract
An assessment of the concentrations of thirteen different therapeutic pharmaceutical compounds was conducted on water samples obtained from different wastewater treatment plants (WWTPs) using solid phase extraction and high- and ultra-high-performance liquid chromatography with mass spectrometry detection (HPLC-MS/MS and UHPLC-MS/MS), was carried out.
The target compounds included ketoprofen and naproxen (anti-inflammatories), bezafibrate (lipid-regulating), carbamazepine (anticonvulsant), metamizole (analgesic), atenolol (β-blocker), paraxanthine (stimulant), fluoxetine (antidepressant), and levofloxacin, norfloxacin, ciprofloxacin, enrofloxacin and sarafloxacin (fluoroquinolone antibiotics).
The relative standard deviations obtained in method were below 11%, while the detection and quantification limits were in the range of 0.3 – 97.4 ng·L-1 and 1.1 – 324.7 ng·L-1, respectively. The water samples were collected from two different WWTPs located on the island of Gran Canaria in Spain over a period of one year. The first WWTP (denoted as WWTP1) used conventional activated sludge for the treatment of wastewater, while the other plant (WWTP2) employed a membrane bioreactor system for wastewater treatment.
Most of the pharmaceutical compounds detected in this study during the sampling periods were found to have concentrations ranging between 0.02 and 34.81 μg·L-1.
Hormonal Contraception and HIV-1 Infection: Medroxyprogesterone Acetate Suppresses Innate and Adaptive Immune Mechanisms
Authors: Huijbregts Richard P. H. , Helton E. Scott , Michel Katherine G. , Sabbaj Steffanie , Richter Holly E. , Goepfert Paul A. , Hel Zdenek 
Published: January 2013

AbstractRecent observational studies indicate an association between the use of hormonal contraceptives and acquisition and transmission of HIV-1. The biological and immunological mechanisms underlying the observed association are unknown. Depot medroxyprogesterone acetate (DMPA) is a progestin-only injectable contraceptive that is commonly used in regions with high HIV-1 prevalence. Here we show that medroxyprogesterone acetate (MPA) suppresses the production of key regulators of cellular and humoral immunity involved in orchestrating the immune response to invading pathogens. MPA inhibited the production of interferon (IFN)-γ, IL-2, IL-4, IL-6, IL-12, TNFα, macrophage inflammatory protein-1α (MIP-1α), and other cytokines and chemokines by peripheral blood cells and activated T cells and reduced the production of IFNα and TNFα by plasmacytoid dendritic cells in response to Toll-like receptor-7, -8, and -9 ligands. Women using DMPA displayed lower levels of IFNα in plasma and genital secretions compared with controls with no hormonal contraception. In addition, MPA prevented the down-regulation of HIV-1 coreceptors CXCR4 and CCR5 on the surface of T cells after activation and increased HIV-1 replication in activated peripheral blood mononuclear cell cultures. The presented results suggest that MPA suppresses both innate and adaptive arms of the immune system resulting in a reduction of host resistance to invading pathogens.
Ontogeny of the Adrenal Gland in the Spiny Mouse, With Particular Reference to Production of the Steroids Cortisol and Dehydroepiandrosterone
Authors: Quinn Tracey A. , Ratnayake Udani , Dickinson Hayley , Nguyen Tri-Hung , McIntosh Michelle , Castillo-Melendez Margie , Conley Alan J. , Walker David W. 
Published: January 2013

Abstract
Synthesis of the androgen dehydroepiandrosterone (DHEA) by the fetal adrenal gland is important for placental estrogen production and may also be important for modulating the effects of glucocorticoids on the developing brain. The presence of cortisol in spiny mouse (Acomys cahirinus) blood led us to determine whether the adrenal gland of this precocial rodent also synthesized DHEA. Cytochrome P450 enzyme 17α-hydroxylase/17,20-lyase (P450c17), cytochrome-b5 (Cytb5), and 3β-hydroxysteroid dehydrogenase (3βHSD) were detected in the adrenal gland from 30 days gestation (term = 39 days), and DHEA, cortisol, and aldosterone were detected in fetal plasma from this time. Plasma DHEA concentrations increased 4-fold, whereas cortisol concentrations decreased from day 30 of gestation until the day of birth. Explant culture of fetal adrenal tissue showed that DHEA was produced from exogenous pregnenolone, and thus, the DHEA in the fetal circulation is likely to be of fetal origin. Clear zonation of the fetal adrenal cortex was evident by 38 days gestation when expression of Cytb5 was present throughout the cortex, and coexpression of P450c17 and Cytb5 occurred in the zona reticularis and fasciculata. 3βHSD was expressed in the cortex from at least 30 days gestation and decreased as term approached, consistent with the fall of cortisol in late gestation in this species. These results show that the spiny mouse adrenal gland, like that of the human fetus, can synthesize and secrete DHEA from at least 30 days (relative gestation length, 30 days of a 39-day gestation, 0.76) of gestation, and DHEA may have important roles in placental biosynthesis of estrogens and in modulating the actions of glucocorticoids in the developing brain in this species.
Phosphorylation of IGFBP-1 at Discrete Sites Elicits Variable Effects on IGF-I Receptor Autophosphorylation
Authors: Abu Shehab Majida , Iosef Cristiana , Wildgruber Robert , Sardana Girish , Gupta Madhulika B. 
Published: January 2013

AbstractWe previously demonstrated that hypoxia and leucine deprivation cause hyperphosphorylation of IGF-binding protein-1 (IGFBP-1) at discrete sites that markedly enhanced IGF-I affinity and inhibited IGF-I-stimulated cell growth. In this study we investigated the functional role of these phosphorylation sites using mutagenesis. We created three IGFBP-1 mutants in which individual serine (S119/S169/S98) residues were substituted with alanine and S101A was recreated for comparison. The wild-type (WT) and mutant IGFBP-1 were expressed in Chinese hamster ovary cells and IGFBP-1 in cell media was isolated using isoelectric-focusing-free-flow electrophoresis. BIACore analysis indicated that the changes in IGF-I affinity for S98A and S169A were moderate, whereas S119A greatly reduced the affinity of IGFBP-1 for IGF-I (100-fold, P &lt; .0001). Similar results were obtained with S101A. The IGF-I affinity changes of the mutants were reflected in their ability to inhibit IGF-I-induced receptor autophosphorylation. Employing receptor-stimulation assay using IGF-IR-overexpressing P6 cells, we found that WT-IGFBP-1 inhibited IGF-IRβ autophosphorylation (∼2-fold, P &lt; .001), possibly attributable to sequestration of IGF-I. Relative to WT, S98A and S169A mutants did not inhibit receptor autophosphorylation. S119A, on the other hand, greatly stimulated the receptor (2.3-fold, P &lt; .05). The data with S101A matched S119A. In summary, we show that phosphorylation at S98 and S169 resulted in milder changes in IGF-I action; nonetheless most dramatic inhibitory effects on the biological activity of IGF-I were due to IGFBP-1 phosphorylation at S119. Our results provide novel demonstration that IGFBP-1 phosphorylation at S119 can enhance affinity for IGF-I possibly through stabilization of the IGF-IGFBP-1 complex. These data also propose that the synergistic interaction of distinct phosphorylation sites may be important in eliciting more pronounced effects on IGF-I affinity that needs further investigation.
Steigerung der zeitlichen Auflösung von PIV-Systemen mittels Wavelet-Transformation
Authors: Hermle Georg , Lawerenz Martin 
Published: January 2013

Zusammenfassung
Das in diesem Artikel beschriebene Auswerteverfahren ermöglicht für Particle Image Velocimetry (PIV) Messysteme mit geringen Messraten die zeitlich aufgelöste Darstellung hochfrequenter, instationärer Strömungseffekte. Das Verfahren bestimmt die Phasenlage des Phänomens mittels Wavelet-Transformation für jede PIV-Messung. Die Messungen können entsprechend der Phasenlage geordnet und somit die zeitliche Entwicklung des Phänomens über eine Periode dargestellt werden. Die Methode wird anhand des instationären Phänomens der Kármánschen Wirbelstraße auf seine Funktionsfähigkeit überprüft.
Un paradigme innovant et puissant pour remédier à la crise du management : le « servant leadership »
Authors: Belet Daniel 
Published: January 2013

Résumé Cet article présente le paradigme de leadership innovant et peu connu en France du « servant leadership ». Celui-ci procède d’une philosophie managériale alternative qui s’avère particulièrement intéressante et pertinente pour remédier à la crise endémique du management des hommes et du leadership que connaissent beaucoup d’organisations et pour améliorer leurs performances sociales et économiques. Il propose en effet d’autres principes et surtout d’autres pratiques de management des hommes qui ont le mérite d’être plus éthiques et donc plus satisfaisantes pour les collaborateurs tout en améliorant très sensiblement la mobilisation du potentiel humain de l’organisation. Dans le contexte actuel de crise des systèmes de management traditionnels hiérarchiques et bureaucratiques hérités de « l’âge industriel », cet autre paradigme de leadership a le mérite d’ouvrir la voie vers un nouvel « humanisme managérial » capable de réconcilier les impératifs d’efficacité économique et le bien - être au travail des collaborateurs. Codes JEL : L21, L26