bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical Activity of Eltrombopag (SB-497115), an Oral, Nonpeptide Thrombopoietin Receptor Agonist
Authors: Erickson-Miller Connie L. , Delorme Evelyne , Tian Shin-Shay , Hopson Christopher B. , Landis Amy J. , Valoret Elizabeth I. , Sellers Teresa S. , Rosen Jon , Miller Stephen G. , Luengo Juan I. , Duffy Kevin J. , Jenkins Julian M. 
Published: November 2008

Abstract
Eltrombopag is a first-in-class, orally bioavailable, small-molecule, nonpeptide agonist of the thrombopoietin receptor (TpoR), which is being developed as a treatment for thrombocytopenia of various etiologies. In vitro studies have demonstrated that the activity of eltrombopag is dependent on expression of TpoR, which activates the signaling transducers and activators of transcription (STAT) and mitogen-activated protein kinase signal transduction pathways. The objective of this preclinical study is to determine if eltrombopag interacts selectively with the TpoR to facilitate megakaryocyte differentiation in platelets. Functional thrombopoietic activity was demonstrated by the proliferation and differentiation of primary human CD34+ bone marrow cells into CD41+ megakaryocytes. Measurements in platelets in several species indicated that eltrombopag specifically activates only the human and chimpanzee STAT pathways. The in vivo activity of eltrombopag was demonstrated by an increase of up to 100% in platelet numbers when administered orally (10 mg/kg per day for 5 days) to chimpanzees. In conclusion, eltrombopag interacts selectively with the TpoR without competing with Tpo, leading to the increased proliferation and differentiation of human bone marrow progenitor cells into megakaryocytes and increased platelet production. These results suggest that eltrombopag and Tpo may be able to act additively to increase platelet production.
Epigenetic Reprogramming of IGF1 and Leptin Genes by Serum Deprivation in Multipotential Mesenchymal Stromal Cells
Authors: Sanchez Cecilia , Oskowitz Adam , Pochampally Radhika R. 
Published: November 2008

AbstractRecent studies on the therapeutic effect of multipotential mesenchymal stem cells (MSCs) in various models of injury have shown that paracrine factors secreted by MSCs are responsible for tissue repair with very little engraftment. In this study we tested the hypothesis that MSCs under stress undergo epigenetic modifications that direct secretion of paracrine factors responsible for tissue repair. Microarray assays of MSCs that had been deprived of serum (SD-MSCs), to induce stress, demonstrated an increase in the expression of several angiogenic, prosurvival, and antiapoptotic factors, including insulin-like growth factor 1 (IGF1) and leptin. Real-time polymerase chain reaction assays demonstrated a &gt;200-fold increase in the expression of IGF1 and leptin in SD-MSCs. Chromatin immunoprecipitation of SD-MSCs revealed histone tail modifications consistent with transcriptional activation of IGF1 and leptin promoters in a reversible manner. To identify the functional significance of the epigenetic changes in stressed MSCs, we tested the prosurvival properties of SD-MSCs and the ability of conditioned medium from SD-MSCs to enhance survival of apoptotic cancer cells. First, we showed that SD-MSCs are more resistant to oxidative damage than MSCs using alkaline comet assays. Next, we demonstrated that conditioned medium from SD-MSCs decreased staurosporin-induced cell death in the KHOS osteosarcoma cell line, and that this effect was partially reversed by immunodepletion of IGF1 or leptin from the conditioned medium. In conclusion, we demonstrate that serum deprivation induces epigenetic changes in MSCs to upregulate the expression of the proangiogenic and antiapoptotic factors IGF1 and leptin.
A STUDY OF THE INCIDENCE, MORTALITY AND FATALITY OF DIPHTHERIA
Authors: Deacon W. J. V. 
Published: November 2008

Diptheria is a disease of childhood. Seventy per cent of all cases and ninety per cent of all deaths occur under fifteen years of age. More boys than girls and more women than men have diphtheria. The fatality rate is higher for males than for females.
Potential role of formaldehyde in the mechanism of action of ascorbigens on the basis of BioArena studies
Authors: Kátay György , Ott Péter G. , Kátay Edit , Magyar Donát , Tyihák Ernő 
Published: November 2008

AbstractThe effect of ascorbigen and 1′‐methylascorbigen as a model compound pair was studied on the phytopathogenic bacterium Pseudomonas savastanoi pv. phaseolicola in the BioArena experimental system after overpressured layer chromatography. Results showed a characteristic, strong antibacterial effect of 1′‐methylascorbigen and weak effect of ascorbigen present on the adsorbent layer as chromatographic spot. Addition of formaldehyde capture compounds (l‐arginine, glutathione, dimedone) partially or totally reduced the antibacterial effect of 1′‐methylascorbigen and ascorbigen. On adding Cu(II) ions—which mobilize and coordinate formaldehyde—to the culture medium, the antibacterial effect of both compounds became stronger. It is supposed that the weak antibacterial effect of ascorbigen may have originated from the 1′‐methylascorbigen formed in situ on the adsorbent layer by partial enzymatic methylation of ascorbigen. Copyright © 2008 John Wiley & Sons, Ltd.
Comparison of impulsive and premeditated perpetrators of intimate partner violence
Authors: Stanford Matthew S. , Houston Rebecca J. , Baldridge Robyn M. 
Published: November 2008

AbstractViolence occurs in four to five million intimate relationships each year in the United States. Past research has investigated the concept of batterer subtypes based on the nature of the violent behavior. To extend this research, the present study used the Impulsive/Premeditated Aggression Scale (IPAS) along with a battery of relevant self‐report measures in a sample of men (N = 113) convicted of domestic violence and court ordered into an intervention program. Batterers whose violence was classified as premeditated scored higher on psychopathic traits and a measure of treatment rejection. Batterers whose violence was classified as impulsive in nature reported a wider range of serious psychopathology. It is suggested that the use of a bimodal classification (Impulsive/Premeditated) in batterers may have significant clinical and legal policy implications. Copyright © 2008 John Wiley & Sons, Ltd.
Without Thinking: Impulsive Aggression and Criminal Responsibility
Authors: Shuman Daniel W. , Gold Liza H. 
Published: November 2008

AbstractIn the U.S. the decision to impose criminal responsibility rests on an assumption about the defendant's decision to engage in proscribed conduct. We punish only those who we believe had the capacity to make a choice. In an increasingly violent world, the criminal law and the assumptions upon which it rests are relentlessly tested. A new generation of neuro‐imaging technologies offers to provide insights into structural and functional abnormalities in the brain that may limit the autonomy of many dangerous offenders and unravel the fabric of the criminal justice system. How will the results of these technologies be received by the courts—are they relevant to existing formulations of the prima facie case, the insanity defense, or mitigation of sentence; will changes in the science or the law be required to accommodate this knowledge? The new generation of technologies may appropriately play a role in assessing culpable mental states only if they are also reliable. This short article takes on these and a host of other related questions at the intersection between science, law, and science fiction. Copyright © 2008 John Wiley & Sons, Ltd.
CXCR3‐deficiency protects influenza‐infected CCR5‐deficient mice from mortality
Authors: Fadel Shaza A. , Bromley Shannon K. , Medoff Benjamin D. , Luster Andrew D. 
Published: November 2008

AbstractMice lacking the chemokine receptor CCR5 are susceptible to mortality from a normally non‐lethal influenza infection. Here we found that CXCR3‐deficiency rescued CCR5‐deficient (CCR5−/−) mice from influenza‐induced mortality. The number of mononuclear phagocytes in the airways was transiently increased in CCR5−/− mice but not in CXCR3‐CCR5 double‐deficient mice. Antigen‐specific CXCR3‐CCR5 double‐deficient CD8 effector cells were less efficient at entering the airways compared with WT or CCR5−/− CD8 effector cells. The decrease in inflammatory cell infiltrates in CXCR3‐CCR5 double‐deficient‐infected mice correlated with a decrease in CCL2 and IFN‐γ production in the airways. Finally, CXCR3‐CCR5 double‐deficient mice that survived the primary viral challenge were protected from a lethal secondary challenge, indicating that T‐cell‐mediated protective memory was not compromised in mice lacking these chemokine receptors. In conclusion, CXCR3‐deficiency attenuated the lethal cellular immune response in CCR5−/− influenza‐infected mice without hindering viral clearance or long‐term immunity.
From phagocyte diversity and activation to probiotics: Back to Metchnikoff
Authors: Mantovani Alberto 
Published: November 2008

AbstractIn this issue of the European Journal of Immunology, Siamon Gordon gives a detailed account of Metchnikoff's life and his achievements (Eur. J. Immunol. 2008. 38: 3257–3264). Looking back at the roots of innate immunity stimulates reflections on open issues in the field. Here, I give a personal view of some of these issues, including myeloid‐derived suppressor cells, macrophage polarization and adaptive responses of mononuclear phagocytes.
Forecasting exchange rate volatility: a multiple horizon comparison using historical, realized and implied volatility measures
Authors: Siu David T. L. , Okunev John 
Published: November 2008

AbstractRecent studies suggest realized volatility provides forecasts that are as good as option‐implied volatilities, with improvement stemming from the use of high‐frequency data instead of a long‐memory specification. This paper examines whether volatility persistence can be captured by a longer dataset consisting of over 15 years of intra‐day data. Volatility forecasts are evaluated using four exchange rates (AUD/USD, EUR/USD, GBP/USD, USD/JPY) over horizons ranging from 1 day to 3 months, using an expanded set of short‐range and long‐range dependence models. The empirical results provide additional evidence that significant incremental information is found in historical forecasts, beyond the implied volatility information for all forecast horizons. Copyright © 2008 John Wiley & Sons, Ltd.
Historical roots of poverty: A symposium
Authors: Bowden Sue , Mosley Paul 
Published: November 2008

AbstractThe current anti‐poverty wave, beginning in the 1990s, has not been deeply influenced by the processes which caused underdevelopment in the past. This is a pity, because historical awareness can help define the processes and institutions which have caused poverty in the past, and provide ideas from the past which can inspire present‐day policy. The essays in this volume all use primary source materials to open up pathways towards the better understanding of present‐day poverty dynamics in the developing world. Copyright © 2008 John Wiley & Sons, Ltd.
Spatial and temporal variability of cloudiness in Poland, 1971–2000
Authors: Filipiak Janusz , Miȩtus Mirosław 
Published: November 2008

AbstractThe study concerns research of the most important features of temporal and spatial structure of cloudiness variability in the area of Poland in the period 1971–2000 using the data from 41 synoptic stations. For all the stations the seasonal and annual values of total cloudiness were calculated, as well as the frequency of total cloudiness, cloud base heights and cloudiness in levels. The analysis by means of the empirical orthogonal functions made it possible to establish the dominant modes of the cloudiness variability in Poland. Mean annual and seasonal cloudiness can be described by means of no more than five dominating eigenvectors presenting the crucial role of circulation influence on the local cloudiness field. Copyright © 2008 Royal Meteorological Society
Microencapsulation of protein‐loaded polysaccharide particles within poly(D,L‐lactic‐co‐glycolic acid) microspheres using S/O/W: characterization and release studies
Authors: Yuan Weien , Wu Fei , Jin Tuo 
Published: November 2008

AbstractThis report demonstrates a process to form polysaccharide glassy particles without water–oil or water–air interfaces as well as ionic polymers and its application in formulating sustained‐release dosage forms for structurally delicate proteins. When a co‐solution containing dextran and polyethylene glycol (PEG) was subjected to freeze‐drying, the dextran separated out of the solution to form dispersed phases surrounded by a PEG‐rich continuous phase and was solidified during subsequent lyophilization to fine glassy particles, 1–2 µm in diameter. Water‐soluble proteins can easily be loaded in these glassy particles due to preferential partition and become resistant to organic solvents simply by adding them into the dextran‐PEG co‐solution. After washing away the PEG continuous phase with organic solvents, the protein‐containing glassy particles can be suspended in a hydrophobic polymer solution and formulated into various pharmaceutical dosage forms and medical devices for sustained‐release protein delivery. In the present study, myoglobin, bovine serum albumin (BSA), andβ‐galactosidase (β‐gal) were formulated in PLGA mcirospheres and as model proteins using this glassy particulate approach, and subjected to a series of assays for release kinetics, structural integrity, and bioactivity. The experimental results indicated that this system offered well preserved protein integrity and bioactivity as well as significantly improved protein release kinetics. Copyright © 2008 John Wiley & Sons, Ltd.
Distribution of microbial terpenoid lipid cyclases in the global ocean metagenome
Authors: Pearson Ann , Rusch Douglas B 
Published: November 2008

Abstract
The bacterial terpenoid lipids known as hopanoids are fundamental tools for interpreting ancient microbial communities. Their degradation products, the hopanes, are found in sedimentary rocks throughout the geologic record. These compounds are presumed to be analogous to the sterols of eukaryotes, yet although the eukaryotic requirement for sterols is universal, hopanoid biosynthetic capacity is not ubiquitous among marine bacteria. Among the 9.8 million shotgun reads from the Sorcerer II Global Ocean Sampling (GOS) expedition, 148 contain putative coding sequence for bacterial squalene-hopene cyclases (SHCs). SHCs encoded by α-Proteobacteria potentially related to Rhodospirillaceae dominate these hits, especially in the open ocean and in tropical regions. Planctomycetes and β-Proteobacteria contribute more SHC-encoding sequences, and therefore presumably more hopanoid production, to coastal and temperate environments. Although sequences nominally related to α- and β-Proteobacteria outnumber other taxa in marine and coastal environments, there is large phylogenetic distance between GOS sequences and known species. Assuming that the environments sampled here are broadly representative of a wide range of surface ocean climates, depositional settings and temporal periods, the data suggest a fundamental function for Proteobacteria in the development of the geologic record of hopanes.
L-Lysine uptake in giant vesicles from cardiac ventricular sarcolemma: two components of cationic amino acid transport
Authors: Lu Xiaodong , Zheng Ruifang , Gonzalez Jorge , Gaspers Lawrence , Kuzhikandathil Eldo , Peluffo R. Daniel 
Published: November 2008

Cationic L-amino acids enter cardiac-muscle cells through carrier-mediated transport. To study this process in detail, L-[14C]lysine uptake experiments were conducted within a 103-fold range of L-lysine concentrations in giant sarcolemmal vesicles prepared from rat cardiac ventricles. Vesicles had a surface-to-volume ratio comparable with that of an epithelial cell, thus representing a suitable system for initial uptake rate studies. Two Na+-independent, N-ethylmaleimide-sensitive uptake components were found, one with high apparent affinity (Km=222±71 μM) and low transport capacity (Vmax=121±36 pmol/min per mg of vesicle protein) and the other with low apparent affinity (Km=16±4 mM) and high capacity (Vmax=4.0±0.4 nmol/min per mg of vesicle protein). L-Lysine uptake mediated by both components was stimulated by the presence of intravesicular L-lysine as well as by valinomycin-induced membrane hyperpolarization. Altogether, this behaviour is consistent with the functional properties of the CAT-1 and CAT-2A members of the system y+ family of cationic amino acid transporters. Furthermore, mRNA transcripts for these two carrier proteins were identified in freshly isolated rat cardiac myocytes, the amount of CAT-1 mRNA, relative to β-actin, being 33-fold larger than that of CAT-2A. These two transporters appear to function simultaneously as a homoeostatic device that supplies cardiac-muscle cells with cationic amino acids under a variety of metabolic conditions. Analysis of two carriers acting in parallel with such an array of kinetic parameters shows significant activity of the low-affinity component even at amino acid plasma levels far below its Km.
Fetal programming alters reactive oxygen species production in sheep cardiac mitochondria
Authors: von Bergen Nicholas H. , Koppenhafer Stacia L. , Spitz Douglas R. , Volk Kenneth A. , Patel Sonali S. , Roghair Robert D. , Lamb Fred S. , Segar Jeffrey L. , Scholz Thomas D. 
Published: November 2008

Exposure to an adverse intrauterine environment is recognized as an important risk factor for the development of cardiovascular disease later in life. Although oxidative stress has been proposed as a mechanism for the fetal programming phenotype, the role of mitochondrial O2•− (superoxide radical) production has not been explored. To determine whether mitochondrial ROS (reactive oxygen species) production is altered by in utero programming, pregnant ewes were given a 48-h dexamethasone (dexamethasone-exposed, 0.28 mg·kg−1 of body weight·day−1) or saline (control) infusion at 27–28 days gestation (term=145 days). Intact left ventricular mitochondria and freeze-thaw mitochondrial membranes were studied from offspring at 4-months of age. AmplexRed was used to measure H2O2 production. Activities of the antioxidant enzymes Mn-SOD (manganese superoxide dismutase), GPx (glutathione peroxidase) and catalase were measured. Compared with controls, a significant increase in Complex I H2O2 production was found in intact mitochondria from dexamethasone-exposed animals. The treatment differences in Complex I-driven H2O2 production were not seen in mitochondrial membranes. Consistent changes in H2O2 production from Complex III in programmed animals were not found. Despite the increase in H2O2 production in intact mitochondria from programmed animals, dexamethasone exposure significantly increased mitochondrial catalase activity, whereas Mn-SOD and GPx activities were unchanged. The results of the present study point to an increase in the rate of release of H2O2 from programmed mitochondria despite an increase in catalase activity. Greater mitochondrial H2O2 release into the cell may play a role in the development of adult disease following exposure to an adverse intrauterine environment.
GS52 Ecto-Apyrase Plays a Critical Role during Soybean Nodulation
Authors: Govindarajulu Manjula , Kim Sung-Yong , Libault Marc , Berg R. Howard , Tanaka Kiwamu , Stacey Gary , Taylor Christopher G. 
Published: November 2008

Abstract
Apyrases are non-energy-coupled nucleotide phosphohydrolases that hydrolyze nucleoside triphosphates and nucleoside diphosphates to nucleoside monophosphates and orthophosphates. GS52, a soybean (Glycine soja) ecto-apyrase, was previously shown to be induced very early in response to inoculation with the symbiotic bacterium Bradyrhizobium japonicum. Overexpression of the GS52 ecto-apyrase in Lotus japonicus increased the level of rhizobial infection and enhanced nodulation. These data suggest a critical role for the GS52 ecto-apyrase during nodulation. To further investigate the role of GS52 during nodulation, we used RNA interference to silence GS52 expression in soybean (Glycine max) roots using Agrobacterium rhizogenes-mediated root transformation. Transcript levels of GS52 were significantly reduced in GS52 silenced roots and these roots exhibited reduced numbers of mature nodules. Development of the nodule primordium and subsequent nodule maturation was significantly suppressed in GS52 silenced roots. Transmission electron micrographs of GS52 silenced root nodules showed that early senescence and infected cortical cells were devoid of symbiosome-containing bacteroids. Application of exogenous adenosine diphosphate to silenced GS52 roots restored nodule development. Restored nodules contained bacteroids, thus indicating that extracellular adenosine diphosphate is important during nodulation. These results clearly suggest that GS52 ecto-apyrase catalytic activity is critical for the early B. japonicum infection process, initiation of nodule primordium development, and subsequent nodule organogenesis in soybean.
Topical tacrolimus 0.1% ointment in the treatment of localized scleroderma. An open label clinical and histological study
Authors: STEFANAKI Christina , STEFANAKI Kalliopi , KONTOCHRISTOPOULOS George , ANTONIOU Christina , STRATIGOS Alexander , NICOLAIDOU Electra , GREGORIOU Stamatis , KATSAMBAS Andreas 
Published: November 2008

ABSTRACTLocalized scleroderma or morphea, although a self‐limited and benign disease, may leave substantial physical and cosmetic deformity necessitating treatment but treatment remains to date unsatisfactory. The aim of our study was to evaluate the efficacy of topical tacrolimus ointment in the treatment of morphea. Thirteen patients with morphea used tacrolimus 0.1% cream b.i.d. without occlusion for 4 months. Patients were followed up for up to a year. A 4‐mm biopsy was taken before starting treatment in seven patients and 4 months after continuous use of tacrolimus 0.1% ointment, next to the previous biopsy site. Masson trichrome and elastica stains were performed to evaluate the distribution of elastic fibers as well as the streptavidin‐biotin horseradish peroxide immunohistochemical method for the detection of CD20/L‐26, CD3, CD8, CD4, CD1a, human leukocyte antigen‐DR and CD25. Four patients had a less than 25% improvement, two patients responded by 50–70% and the remaining seven by more than 70%. Patients with thick, well‐established lesions responded poorly in comparison to others with less thick and more erythematous ones. Patients with mild‐to‐moderate fibrosis histologically were more likely to improve after treatment, while the lymphocytic infiltrate decreased regardless of initial degree before treatment. It was concluded that topical tacrolimus 0.1% cream may be used in patients with morphea, particularly with early inflammatory lesions, even as a first‐line treatment.
Postmenopausal frontal fibrosing alopecia in a Japanese woman with Sjögren's syndrome
Authors: SATO Makito , SAGA Kenji , TAKAHASHI Hiroyuki 
Published: November 2008

ABSTRACTPostmenopausal frontal fibrosing alopecia (PFFA) is a rare alopecia that develops in the frontoparietal scalp of postmenopausal women. Etiology of PFFA is unknown. Most of cases of PFFA have been reported in European and North American countries. Herein, we report a Japanese case of PFFA associated with Sjögren's syndrome. A 66‐year‐old woman had had slowly progressive, band‐like, scarring alopecia on her frontoparietal scalp. Hair follicles on the margin showed follicular keratosis. Histologically, fibrosis and lymphocytic infiltration were mild. This case suggests that PFFA may show mild inflammatory reaction and mild fibrosis in Japanese women. The association with immunological disorders including Sjögren's syndrome should be studied further.