bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initiation of Dopaminergic Differentiation of Nurr1− Mesencephalic Precursor Cells Depends on Activation of Multiple Mitogen-Activated Protein Kinase Pathways
Authors: Sabolek Michael , Baumann Bernd , Heinrich Maria , Meyer Anne K. , Herborg Anna , Liebau Stefan , Maisel Martina , Hermann Andreas , Ventz Katharina , Schwarz Johannes , Wirth Thomas , Storch Alexander 
Published: May 2009

Abstract
Interleukin-1 (IL-1) plays a pivotal role in terminal dopaminergic differentiation of midbrain-derived neural precursor cells already committed to the mesencephalic dopaminergic phenotype (named mdNPCs for mesencephalic dopaminergic neural precursor cells). Here we characterized the molecular events in long-term expanded rat nuclear receptor related-1− (Nurr1−) mdNPCs in response to IL-1β during their terminal dopaminergic specification. We showed that IL-1β induced a rapid induction of mRNA of dopaminergic key fate-determining transcription factors, such as Nurr1 and Pitx3, and a subsequent increase of tyrosine hydroxylase protein as an early marker for dopaminergic neurons in vitro. These effects of IL-1β were specific for mdNPCs and were not observed in striatal neural precursor cells (NPCs). Surprisingly, IL-1β did not activate the NF-κB pathway or the transcription factor activating protein 1 (AP-1), but inhibition of nuclear translocation of NF-κB by SN50 facilitated IL-1β-induced Nurr1 expression and dopaminergic differentiation of mdNPCs. Incubation of mdNPCs with IL-1β led to a rapid phosphorylation of ERK1/2 and p38 mitogen-activated protein (MAP) kinases within 1 to 3 hours, whereas Jun kinase was not phosphorylated in response to IL-1β. Consistently, inhibition of the ERK1/2 pathway or p38 MAP kinase blocked Nurr1 upregulation and further dopaminergic specification of mdNPCs, but not differentiation into MAP2ab+ neurons. IL-1 receptor antagonist did not block early dopaminergic differentiation events, suggesting that the effects of IL-1β are not mediated through activation of IL-1 receptor type I. Our results indicate that induction of terminal dopaminergic specification of Nurr1− mdNPCs by IL-1β depends on activation of the ERK1/2 and p38 MAP kinase pathway.
Disclosure of potential conflicts of interest is found at the end of this article.
Ionizing Radiation Induces Ataxia Telangiectasia Mutated-Dependent Checkpoint Signaling and G2 But Not G1 Cell Cycle Arrest in Pluripotent Human Embryonic Stem Cells
Authors: Momčilović Olga , Choi Serah , Varum Sandra , Bakkenist Christopher , Schatten Gerald , Navara Christopher 
Published: May 2009

Abstract
Human embryonic stem (ES) cells are highly sensitive to environmental insults including DNA damaging agents, responding with high levels of apoptosis. To understand the response of human ES cells to DNA damage, we investigated the function of the ataxia telangiectasia mutated (ATM) DNA damage signaling pathway in response to γ-irradiation. Here, we demonstrate for the first time in human ES cells that ATM kinase is phosphorylated and properly localized to the sites of DNA double-strand breaks within 15 minutes of irradiation. Activation of ATM kinase resulted in phosphorylation of its downstream targets: Chk2, p53, and Nbs1. In contrast to murine ES cells, Chk2 and p53 were localized to the nucleus of irradiated human ES cells. We further show that irradiation resulted in a temporary arrest of the cell cycle at the G2, but not G1, phase. Human ES cells resumed cycling approximately 16 hours after irradiation, but had a fourfold higher incidence of aberrant mitotic figures compared to nonirradiated cells. Finally, we demonstrate an essential role of ATM in establishing G2 arrest since inhibition with the ATM-specific inhibitor KU55933 resulted in abolishment of G2 arrest, evidenced by an increase in the number of cycling cells 2 hours after irradiation. In summary, these results indicate that human ES cells activate the DNA damage checkpoint, resulting in an ATM-dependent G2 arrest. However, these cells re-enter the cell cycle with prominent mitotic spindle defects.
Disclosure of potential conflicts of interest is found at the end of this article.
Smad, PI3K/Akt, and Wnt-Dependent Signaling Pathways Are Involved in BMP-4-Induced ESC Self-Renewal
Authors: Lee Min Young , Lim Hyun Woo , Lee Sang Hun , Han Ho Jae 
Published: May 2009

Abstract
It is known that bone morphogenetic protein 4 (BMP-4) has a diverse effect on ESCs. However, its precise mechanism in mouse ESCs is not fully understood. We evaluated the effect of BMP-4 on ESC proliferation and its related signal cascades in this study. BMP-4 significantly increased the level of [3H]-thymidine incorporation in time- (≥8 hours) and dose- (≥10 ng/ml) dependent manners. Additionally, BMP-4 increased cyclin D1 and decreased p27kip1 expression values in a time-dependent manner. The increases in BMP-4-induced [3H]-thymidine incorporation and cyclin D1 expression were inhibited by the BMP-4 receptor antagonist noggin. BMP-4 increased Wnt1 expression. Wnt1 expression was attenuated by Smad4 small interfering RNA (siRNA), and BMP-4-induced cyclin D1 expression was inhibited by Smad4 and Wnt1 siRNAs. BMP-4 also activated β-catenin, which was blocked by Smad4 and Wnt1 siRNAs. In addition, BMP-4 induced Akt phosphorylation. BMP-4-induced β-catenin activation and cyclin D1 expression were attenuated by phosphatidyl inositol 3-kinase (PI3K) siRNA and Akt inhibitor. Additionally, downregulation of Smad4, Wnt1, and PI3K expression by siRNA decreased the levels of pluripotency marker mRNAs of ESCs, including Oct4, Sox2, and FoxD3. Our results suggested that BMP-4-induced [3H]-thymidine incorporation was significantly attenuated by Smad4, Wnt1, and PI3K knockdown. In conclusion, BMP-4 contributed to the maintenance of cell proliferation and the pluripotent state by Smad, PI3K/Akt, and Wnt1/β-catenin in mouse ESCs.
Disclosure of potential conflicts of interest is found at the end of this article.
A Complex Role for FGF-2 in Self-Renewal, Survival, and Adhesion of Human Embryonic Stem Cells
Authors: Eiselleova Livia , Matulka Kamil , Kriz Vitezslav , Kunova Michaela , Schmidtova Zuzana , Neradil Jakub , Tichy Boris , Dvorakova Dana , Pospisilova Sarka , Hampl Ales , Dvorak Petr 
Published: May 2009

Abstract
The transcription program that is responsible for the pluripotency of human ESCs (hESCs) is believed to be comaintained by exogenous fibroblast growth factor-2 (FGF-2), which activates FGF receptors (FGFRs) and stimulates the mitogen-activated protein kinase (MAPK) pathway. However, the same pathway is stimulated by insulin receptors, insulin-like growth factor 1 receptors, and epidermal growth factor receptors. This mechanism is further complicated by intracrine FGF signals. Thus, the molecular mechanisms by which FGF-2 promotes the undifferentiated growth of hESCs are unclear. Here we show that, in undifferentiated hESCs, exogenous FGF-2 stimulated the expression of stem cell genes while suppressing cell death and apoptosis genes. Inhibition of autocrine FGF signaling caused upregulation of differentiation-related genes and downregulation of stem cell genes. Thus, exogenous FGF-2 reinforced the pluripotency maintenance program of intracrine FGF-2 signaling. Consistent with this hypothesis, expression of endogenous FGF-2 decreased during hESC differentiation and FGF-2 knockdown-induced hESC differentiation. In addition, FGF-2 signaling via FGFR2 activated MAPK kinase/extracellular signal-regulated kinase and AKT kinases, protected hESC from stress-induced cell death, and increased hESC adhesion and cloning efficiency. This stimulation of self-renewal, cell survival, and adhesion by exogenous and endogenous FGF-2 may synergize to maintain the undifferentiated growth of hESCs.
Disclosure of potential conflicts of interest is found at the end of this article.
A Targeted Neuroglial Reporter Line Generated by Homologous Recombination in Human Embryonic Stem Cells
Authors: Xue Haipeng , Wu Sen , Papadeas Sophia T. , Spusta Steve , Swistowska Anna Maria , MacArthur Chad C. , Mattson Mark P. , Maragakis Nicholas J. , Capecchi Mario R. , Rao Mahendra S. , Zeng Xianmin , Liu Ying 
Published: May 2009

Abstract
In this study, we targeted Olig2, a basic helix-loop-helix transcription factor that plays an important role in motoneuron and oligodendrocyte development, in human embryonic stem cell (hESC) line BG01 by homologous recombination. One allele of Olig2 locus was replaced by a green fluorescent protein (GFP) cassette with a targeting efficiency of 5.7%. Targeted clone R-Olig2 (like the other clones) retained pluripotency, typical hESC morphology, and a normal parental karyotype 46,XY. Most importantly, GFP expression recapitulated endogenous Olig2 expression when R-Olig2 was induced by sonic hedgehog and retinoic acid, and GFP-positive cells could be purified by fluorescence-activated cell sorting. Consistent with previous reports on rodents, early GFP-expressing cells appeared biased to a neuronal fate, whereas late GFP-expressing cells appeared biased to an oligodendrocytic fate. This was corroborated by myoblast coculture, transplantation into the rat spinal cords, and whole genome expression profiling. The present work reports an hESC reporter line generated by homologous recombination targeting a neural lineage-specific gene, which can be differentiated and sorted to obtain pure neural progenitor populations.
Disclosure of potential conflicts of interest is found at the end of this article.
Seismic performance of a 20‐story steel‐frame building in Canada
Authors: Yousuf MD , Bagchi Ashutosh 
Published: May 2009

AbstractIn performance‐based seismic design of a structure, the inelastic deformation demand of structural members or system is the primary input, whereas in conventional design procedure the input is the equivalent static loads to represent seismic effects. The National Building Code of Canada (NBCC) 2005 requires that for irregular and buildings higher than 60 m, dynamic analysis must be conducted to calculate seismic design forces and deflection, while for other cases, equivalent static loads can be used for the design. In this paper, the performance of a 20‐story steel moment resisting steel frame building, designed for western part of Canada, has been presented. Simulated and actual (scaled) ground motion records are used to evaluate the dynamic response. While NBCC does not provide any performance‐based design method, various techniques for displacement‐based design have been explored here in the context of the 20‐story building. A wide range of variation amongst these methods in terms of their application and results was found. Amongst these methods the direct displacement‐based design method seems to be more suitable for carrying out the performance‐based design of a building. Copyright © 2009 John Wiley & Sons, Ltd.
Indoor–outdoor distribution and risk assessment of volatile organic compounds in the atmosphere of industrial and urban areas
Authors: Massolo Laura , Rehwagen Martina , Porta Andres , Ronco Alicia , Herbarth Olf , Mueller Andrea 
Published: May 2009

AbstractVolatile organic compounds (VOCs), which play an important part indoors and outdoors, comprise differing compound groups such as n‐alkanes, cycloalkanes, aromatic and chlorinated hydrocarbons and terpenes. In the current study, samples were analyzed from indoor (schools and houses, n = 92) and outdoor (n = 33) air in urban, industrial, semirural and residential areas from the region of La Plata (Argentine) to consider VOC exposure in different types of environments. VOCs were sampled for 1 month during winter for 3 years, with passive 3M monitors. Samples were extracted with CS2 and analyzed by GC/MS detectors. The results show significant differences in concentration and distribution between indoor and outdoor samples, depending on the study area. Most VOCs predominantly originated indoors in urban, semirural and residential areas, whereas an important outdoor influence in the industrial area was observed. In all areas alkanes and aromatic compounds dominated, even though a different chemical distribution was seen. Traffic burden was determined as the major source of outdoor VOC with a benzene/toluene ratio close to 0.5. Indoors, C9–C11 alkanes, toluene and xylenes dominated, caused by human activities. In contrast, in the industrial area higher concentrations of hexane, heptane and benzene occurred outdoors and affected the indoor air significantly. The lifetime cancer risk (LCR) associated to the benzene exposure was calculated for children from the different study areas. For all groups the study showed a LCR value greater than 1 × 10−6 related to the benzene exposure indoors as well outdoors. A value two magnitudes higher was detected indoors in the industrial area, what demonstrates the high risk for children living in this area of La Plata. © 2009 Wiley Periodicals, Inc. Environ Toxicol 25: 339–349, 2010.
Reduced Ternary Rare‐Earth–Transition Metal Tellurides for the Smaller Rare‐Earth Elements. An Exploration and an Explanation of the Marked Stability Differentiation among the Rare‐Earth Elements in These Phases
Authors: Herzmann Nina , Gupta Shalabh , Corbett John D. 
Published: May 2009

AbstractThe existence of further metal‐rich condensed cluster compounds in R–Z–Te systems has been synthetically explored for R = Sc, Y, Pr, Dy, Er, Tm, Yb, Lu and, mainly, Z = Ru, Rh, Pd, Ag, Ir, Pt, Au. Ten new examples of orthorhombic Er7Ni2Te2‐type (Imm2) have been identified and that for Dy7Ir2Te2 has been refined. Seven new examples of other ternary structure types plus X‐ray powder pattern evidence for 14 unknown phases have also been identified. To date the family of ternary R–Z–Te phases appears to be limited to those for R = Sc, Y, and Dy–Lu, a trend that is parallel to but more emphatic than those variations found among parallel cluster halide systems. Stability trends among the halide and especially the telluride series follow the I1 + I2 sums for the R elements well, the larger values of which are considered to reflect better mixing of R and Z valence d orbitals in the more stable phases.
Leaf‐trait relationships of Quercus liaotungensis along an altitudinal gradient in Dongling Mountain, Beijing
Authors: Jian Qi , Keming Ma , Yuxin Zhang 
Published: May 2009

AbstractFew studies have examined leaf‐trait relationships in the distribution of individual species along an environmental gradient. Here we address the issue by testing for the leaf‐trait relationships of Quercus liaotungensis, a dominant deciduous woody species in northern China, along an altitudinal gradient in Dongling Mountain, Beijing. These leaf traits included specific leaf area (SLA), leaf dry matter content (LDMC), and leaf nitrogen, phosphorus, and potassium concentration on mass basis (Nmass, Pmass and Kmass, respectively). Along the altitudinal gradient, negative relationships between SLA and LDMC and Nmass were found, and Nmass, Pmass and Kmass correlated with each other positively. Relationship between Nmass and Pmass was stronger than the ones between Nmass and Kmass, and between Pmass and Kmass. The weak and negative relationship between SLA and Nmass might result from trade‐offs that limit photosynthesis and water use efficiency along the altitudinal gradient, suggesting many environmental factors of local site being the collective forcing of drivers. Out of our expectations, Nmass and Pmass related very weakly to soil N and P, and no significant relationship between Kmass and soil K was found along elevation. These relationships could be used to predict the productivity of the population with changing environment in this region.
Modification of Palm Oil for Anti‐Inflammatory Nutraceutical Properties
Authors: Zainal Zaida , Longman Andrea J. , Hurst Samantha , Duggan Katrina , Hughes Clare E. , Caterson Bruce , Harwood John L. 
Published: May 2009

AbstractPalm oil is one of the most important edible oils in the world. Its composition (rich in palmitate and oleate) make it suitable for general food uses but its utility could be increased if its fatty acid quality could be varied. In this study, we have modified a palm olein fraction by transesterification with the n‐3 polyunsaturated fatty acids, α‐linolenate or eicosapentaenoic acid (EPA). Evaluation of the potential nutritional efficacy of the oils was made using chondrocyte culture systems which can be used to mimic many of the degenerative and inflammatory pathways involved in arthritis. On stimulation of such cultures with interleukin‐1α, they showed increased expression of cyclooxygenase‐2, the inflammatory cytokines tumour necrosis factor‐α (TNF‐α), IL‐1α and IL‐1β and the proteinase ADAMTS‐4. This increased expression was not affected by challenge of the cultures with palm olein alone but showed concentration‐dependent reduction by the modified oil in a manner similar to EPA. These results show clearly that it is possible to modify palm oil conveniently to produce a nutraceutical with effective anti‐inflammatory properties.
Confidence and Gold: German War Finance 1914–1918
Authors: Gross Stephen 
Published: May 2009

In January 1915, Sir William Grenfell Max-Müller, an intelligence officer in the British Foreign Office, recorded the following remark from a German trade journal.As long as the confidence in military and political victory continues, we need not fear our paper system and its consequences. But one sees immediately what would be bound to threaten us in the contrary case—a ruin to avoid which we are compelled to sacrifice the last man and the last penny.1
EARLY NINETEENTH-CENTURY SCOTTISH MILITARY PENSIONERS AS HOMECOMING SOLDIERS
Authors: COOKSON J. E. 
Published: May 2009

ABSTRACTThis article makes use of the data-rich sources, little used by historians, relating to rank and file soldiers, especially those who became Chelsea Hospital outpensioners. It particularly seeks to find out the migration history of such men in the years after Waterloo, focusing on Scots. The conclusion is that Scots were under-represented among soldiers who became imperial settlers. There appear to be good reasons for Scots finding colonial conditions uncongenial, and, in this respect, there was little difference between the ‘Napoleonic’ soldiery and the succeeding generation who belonged more definitely to an imperial service army. Most, in fact, returned to Scotland, and then to that part of the country familiar to them. Moreover, they refute an image of veterans as marginalized men. They are shown, on the whole, to have settled back into civilian society with surprising ease, law-abiding rather than lawless, respected rather than despised or feared.
Direct Conglutination withRickettsia Burneti, the Causal Agent of Q Fever
Authors: Barber H. 
Published: May 2009

Summary1. Direct conglutination has been demonstrated withRickettsia burneti.2. Sera from human volunteers inoculated with killed suspensions ofR. burnetiand from persons who had recovered from an attack of Q fever as well as sera from a small number of healthy blood donors were all examined by the direct conglutination reaction, the haemolytic-complement fixation test and the direct agglutination test. A good correlation was found between the titres of the direct conglutination reaction and the haemolytic complement-fixation test but the results with the direct agglutination test were unreliable.
The Active Immunization of Guinea-Pigs Passively Immunized with Homologous Antitoxic Serum
Authors: Mason J. H. , Robinson Mary , Christensen P. Agerholm 
Published: May 2009

SummaryGroups of guinea-pigs were passively immunized against diphtheria toxin with homologous antitoxic serum so that their sera contained, at the start of the experiment, 1·0, 0·1, 0·01 or 0·001 unit/ml, respectively. They were then actively immunized with one, or two spaced, injections of 0·1 Lf of A.D.F. Two control groups were included, one passively immunized only and the other actively immunized only.Passively produced serum titres of 0·01 and 0·001 unit/ml. did not interfere with active immunization in any demonstrable way.A titre of 0·1 unit/ml. did interfere with active immunization, markedly 4 weeks after the primary, slightly 2 weeks after the secondary, and markedly 14 weeks after the secondary, stimulus.A titre of 1·0 unit/ml. interfered with active immunization, markedly 4 weeks after the primary, and 2 and 14 weeks after the secondary, stimulus. This titre, however, did not completely annul the effect of the primary stimulus. The highest observed serum titre was obtained at the 32nd, instead of at the 4th week, as in the guinea-pigs actively immunized only.In large measure the results confirm those of Barr and her colleagues who found that, in human babies, an initial ‘passive’ titre of 0·04 unit/ml. serum did not interfere with active immunization, whereas a titre of 0·1 unit/ml, led to unsatisfactory immunization.
Clostridium BotulinumTypes A and B Toxin-Antitoxin Reactions
Authors: Fulthorpe A. J. 
Published: May 2009

SummaryC. botulinumtypes A and B toxins required larger amounts of antitoxin for neutralization when fractions of the test dose of toxin were used than would be expected.The degree of this dilution effect, i.e. the dilution ratio, varied with different sera. The dilution ratios with type A sera could be improved by allowing a greater time for combination to occur, or by mixing toxin and antitoxin in high concentration and diluting these mixtures.The dilution ratios of type A sera from horses rose as immunization proceeded, the greatest rise occurring during the 3-month rest period following three small doses of toxoid.A type A serum could be separated into fractions of different dilution ratio by precipitation with increasing concentrations of ammonium sulphate.Type A antitoxins prepared by immunization of groups of guinea-pigs with two doses of toxoid, had dilution ratios far lower than those found in hyperimmune horse sera.The dilution ratios of sera were lower when tested against a toxic toxin than against a more toxoided one.A number of type A sera were tested at one level of test against a number of test toxins. There was no evidence of heterogeneity of the toxins and antitoxins tested.The serum ratios were found to be correlated with the dilution ratios except where the serum ratios exceeded 0·64. Flocculation time was slow and varied from 6 to 48 hr. with different sera tested against the same toxoid.I am greatly indebted to Miss M. Barr for her constant advice and encouragement in the execution of this work and in the preparation of this paper. I am grateful to Dr M. Sterne for the supply ofC. botulinumtype A and B toxins and for the benefit of his experience of animal botulism.
Intensive Breeding of Mice
Authors: Lane-Petter W. 
Published: May 2009

Summary1. Production figures are given for a small mouse colony.2. High productivity depends upon careful selection of breeding stock.3. This selection has been based on an analysis of individual records. Both the keeping and the analysis of records are easy and simple.4. In addition to providing a basis for selection, these records make possible a forecast of future production.I particularly wish to thank Miss D. Lawrence, the animal technician whose skill in looking after this colony has contributed so much to its successful performance.
Production of Non-Infective Particles among Influenza Viruses: Do Changes in Virulence Accompany the von Magnus phenomenon?
Authors: de St Groth S. Fazekas , Moran P. A. P. 
Published: May 2009

SummaryTwo new statistical methods—one parametric, the other non-parametric—are developed to compare the slopes of quantal infectivity curves.Ten influenza strains were examined with the aid of these tests, and the results show that virus yielded by the von Magnus phenomenon (i.e. containing ‘incomplete’ particles) and standard infective virus do not differ in the slope of their infectivity curves.It is concluded that the von Magnus phenomenon yields a mixture of infective and non-infective particles; on this evidence Fulton's suggestion of uniformly changed virulence is untenable.I am greatly indebted to Prof. P. A. P. Moran for helpful discussions of theory, and frequent corrections of statistical technique.