bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal allergy influences p38‐mitogen‐activated protein kinase activity upon microbial challenge in CD14+ monocytes from 2‐year‐old children
Authors: Saghafian‐Hedengren S. , Holmlund U. , Amoudruz P. , Nilsson C. , Sverremark‐Ekström E.
Published: February 2008

Background
The development of allergic diseases is dependent on genetic and environmental factors. It has been shown previously that cord blood mononuclear cells (CBMCs) from infants with parental allergy have altered cytokine profiles upon bacterial encounter; it might be possible that such impairment persists during the early years of childhood.

Objective
The aim of this study was to investigate anti‐microbial responses with regard to p38‐mitogen‐activated protein kinase (MAPK) activity in CD14+ monocytes and IL‐6 release from mononuclear cells in the same group of children at birth and at 2 years of age.

Methods
Paired samples of CBMCs and peripheral blood mononuclear cells (PBMCs) were stimulated with either lipopolysaccharide (LPS) or peptidoglycan in vitro. CD14+ monocytes were analysed for p38‐MAPK activity by flow cytometry, and soluble IL‐6 receptor, soluble glycoprotein130 and IL‐6 release from PBMC cultures were quantified by ELISA.

Results
CBMCs from newborns with allergic mothers tended to have a lower IL‐6 response following an LPS (P=0.09) challenge compared with the group without maternal allergy while p38‐MAPK activation levels did not differ between the groups. PBMCs from 2‐year‐olds with allergic mothers released significantly less (P<0.05) IL‐6 upon peptidoglycan stimuli compared with age‐matched infants with non‐allergic mothers. Infants with allergic mothers displayed markedly reduced CD14+ monocyte p38‐MAPK phosphorylation after LPS (P<0.05) and peptidoglycan (P<0.01) challenge. This altered anti‐microbial response was attributed to maternal allergy rather than to being IgE‐sensitized at 2 years of age.

Conclusion
Monocytes from children with allergic mothers are less responsive to bacterial challenge than monocytes from children with non‐allergic mothers, and this impairment persists during the first 2 years of infancy.
Sulphidoleukotriene release of cord blood basophils in response to allergen stimulation correlates with neither a family history of atopy nor a subsequent development of atopic eczema
Authors: Walaschek C. , Heinzmann A. , Weckmann M. , Kopp M. V.
Published: February 2008

Objective
We tested a possible relationship between sulphidoleukotriene (SLT) release of cord blood (CB) basophils, a family history of atopy (HA) and subsequent development of atopic eczema.

Population and methods
A cohort of 86 neonates were involved (48.8% males; 46.5% with a positive HA+). CB samples were analysed for in vitro SLT release quantified by ELISA, and in a subgroup for basophilic activation (CD 63 expression) by flow cytometry in response to a positive control (anti‐IgE‐receptor antibody), an allergen‐mix (TOP and PTOP), egg white (EW), egg yolk (EY), and the purified allergens β‐lactoglobulin (BLG) and α‐lactalbumin (ALA).

Results
Median concentrations of SLT were 124.2 (negative), 3871.5 (positive), 123.9 (TOP), 128.5 (PTOP), 113.1 (EW), 108.4 (EY), 125.2 (BLG) and 122.3 (ALA) pg/mL. Groups of HA+ and HA– show no difference in all analysed allergens. An allergen‐specific SLT release (defined as SLT>125 pg/mL above individual baseline and a stimulation index >2) was detected in 98% (positive control), 5% (TOP), 7% (BLG), 3% (ALA) and 2% (EW and EY), respectively. After a median observation period of 18 months, n=7 out of 70 children developed an atopic eczema, but we observed no association between CB SLT release (positive response to at least one tested allergen).

Conclusion
Allergen‐specific SLT release is detectable in 15.5% of healthy neonates, irrespective of their family history of atopy. However, early allergen‐specific SLT release is not predictive for the development of atopy.
Mechanisms of pathogenesis and the evolution of parasite virulence
Authors: FRANK S. A. , SCHMID‐HEMPEL P.
Published: February 2008

When studying how much a parasite harms its host, evolutionary biologists turn to the evolutionary theory of virulence. That theory has been successful in predicting how parasite virulence evolves in response to changes in epidemiological conditions of parasite transmission or to perturbations induced by drug treatments. The evolutionary theory of virulence is, however, nearly silent about the expected differences in virulence between different species of parasite. Why, for example, is anthrax so virulent, whereas closely related bacterial species cause little harm? The evolutionary theory might address such comparisons by analysing differences in tradeoffs between parasite fitness components: transmission as a measure of parasite fecundity, clearance as a measure of parasite lifespan and virulence as another measure that delimits parasite survival within a host. However, even crude quantitative estimates of such tradeoffs remain beyond reach in all but the most controlled of experimental conditions. Here, we argue that the great recent advances in the molecular study of pathogenesis provide a way forward. In light of those mechanistic studies, we analyse the relative sensitivity of tradeoffs between components of parasite fitness. We argue that pathogenic mechanisms that manipulate host immunity or escape from host defences have particularly high sensitivity to parasite fitness and thus dominate as causes of parasite virulence. The high sensitivity of immunomodulation and immune escape arise because those mechanisms affect parasite survival within the host, the most sensitive of fitness components. In our view, relating the sensitivity of pathogenic mechanisms to fitness components will provide a way to build a much richer and more general theory of parasite virulence.
The impact of shared ancestral variation on hybrid male lethality – a 16 codon indel in the Drosophila simulans Lhr gene
Authors: NOLTE V. , WEIGEL D. , SCHLÖTTERER C.
Published: February 2008

The Lethal hybrid rescue (Lhr) gene causes hybrid male lethality in crosses between Drosophila simulans and D. melanogaster. Lhr2 is a D. simulans allele, which rescues hybrid males. It has been recently proposed that a 16 codon insertion, which distinguishes the D. melanogaster and the canonical D. simulans allele, and is lacking in Lhr2, may be responsible for the functional divergence of D. melanogaster and D. simulans Lhr alleles. Here, we show that the Lhr2 allele lacking the insertion represents an ancestral polymorphism segregating at a moderate frequency in D. simulans. Crosses of D. melanogaster females to males from two D. simulans strains carrying this deletion showed a severe deficiency of viable hybrid males. Our results suggest that the absence of this insertion alone is not sufficient to explain functional differences between D. melanogaster and D. simulans Lhr alleles.
Social heterosis and the maintenance of genetic diversity at the genome level
Authors: NONACS P. , KAPHEIM K. M.
Published: February 2008

Social heterosis is when individuals in groups or neighbourhoods receive a mutualistic benefit from across‐individual genetic diversity. Although it can be a viable evolutionary mechanism to maintain allelic diversity at a given locus, its efficacy at maintaining genome‐wide diversity is in question when multiple loci are being simultaneously selected. Therefore, we modelled social heterosis in a population of haploid genomes of two‐ or three‐linked loci. With such linkages, social heterosis decreases gametic diversity, but maintains allelic diversity. Genomes tend to survive as complimentary pairs, with alternate alleles at each locus (e.g. the pair AbC and aBc). The outcomes of selection appear similar to fitness epistasis but are novel in the sense that phenotypic interactions occur across rather than within individuals. The model’s results strongly suggest that strong linkage across gene loci actually increases the probability that social heterosis maintains significant genetic diversity at the level of the genome.
Interspecific variation in ejaculate allocation and associated effects on female fitness in seed beetles
Authors: RÖNN J. L. , KATVALA M. , ARNQVIST G.
Published: February 2008

When ejaculates are costly to produce, males are expected to allocate their ejaculate resources over successive matings in a manner that optimizes their reproductive success and this may have important consequences for their mates. In seed beetles (Coleoptera; Bruchidae), ejaculates vary in size across species from weighing less than 1%, up to as much as 8%, of male body weight. Ejaculates contain not only sperm but also a range of additional substances and females in some species gain benefits from receiving large ejaculates. Male ejaculate allocation may thus affect female fitness. Here, we first characterized the pattern of male ejaculate allocation over successive matings in seven‐seed beetle species. We then assessed how this allocation affected female fitness in each species. Although females generally benefited from receiving large ejaculates, the interspecific variation observed both in ejaculate allocation patterns and in their effects on female fitness was remarkably large considering that the species studied are closely related. Our analyses suggest that variation in ejaculate composition is the key, both within and across species. We discuss possible causes for this variation and conclude that coevolution between male ejaculates and female utilization of ejaculate substances has apparently been rapid in this clade.
FATIGUE, CREEP AND CREEP/FATIGUE BEHAVIOUR OF A NICKEL BASE SUPERALLOY AT 700°C
Authors: Hyde T. H. , Xia L. , Becker A. A. , Sun W.
Published: February 2008

Abstract— This paper presents the results of an experimental testing programme to examine the uniaxial creep, low cycle fatigue and creep/fatigue interaction behaviour of a Ni‐base superalloy at 700°C. The material is used in the manufacture of aeroengine turbine discs. A creep continuum damage mechanics model is shown to be capable of accurately predicting the creep and creep rupture behaviour of the material. A healing term has been incorporated into the damage mechanics model to allow the behaviour under creep/fatigue conditions to be described.
SUBINTERFACIAL FRACTURE IN FERRITE‐AUSTENITE JOINTS UNDER MODE—III LOADING
Authors: Zelezny M. F. , Tschegg E. K. , Kirchner H. O. K.
Published: February 2008

Abstract— Circumferentially notched cylindrical specimens are tested in torsion to obtain critical J values from crack resistance curves. The specimens are explosion cladded, half ferrite, half austenite, with the interface perpendicular to the cylinder axis and the circumferential notch at, or parallel to, the interface. Critical J values for crack extension in mode III were found to be a factor 1.1 to 2.1 higher than under comparable mode I loading.
LIMITATIONS ON THE USE OF THE STRESS INTENSITY FACTOR, K, AS A FRACTURE PARAMETER IN THE FATIGUE PROPAGATION OF SHORT CRACKS
Authors: Kfouri A. P.
Published: February 2008

Abstract— It is well known that for very short cracks the stress intensity factor K is not a suitable parameter to estimate the stress level over the small but finite Stage II process zone activation region of size rs near the crack tip, within which crack growth events take place. A critical appreciation of the reasons for the limitations on the applicability of ΔK as a fatigue crack propagation (FCP) parameter, when the crack length a is of the same order of magnitude or smaller than the size of the ‘fatigue‐fracture activation region’, rs is presented. As an alternative to ΔK the range Δσs of the cyclic normal stress at a point situated at the fixed distance s=rs/2, ahead of the crack tip, inside the fatigue‐fracture activation region, is proposed. It is observed that the limitation on the use of ΔK when the crack is short, is mathematical (and not physical) but this inconvenience is easily circumvented if the stress Δσs at the prescribed distance is used instead of ΔK since nowadays Δσs can be obtained numerically by using finite element methods (FEM). It follows that the parameter Δσs is not restricted by the mathematical limitations on ΔK and so it would seem that there is, a priori, no reason why the validity of the parameter Δσs cannot be extended to short cracks. It is shown that if the Paris law is expressed in terms of Δσs (πrrs)½ instead of ΔK the validity of the modified Paris law can be extended to short cracks.

A coherent estimate of the value of the fatigue‐fracture activation region rs is derived in terms of the fatigue limit ΔσFL obtained from S‐N tests and of the threshold value ΔKth obtained from tests on long cracks where both relate to Stage II crack growth that ends in failure, namely, rs= (ΔKth/ΔσFL)2/π. An overall, threshold diagram is presented based on the simple criterion that, for sustained Stage II FCP, Δσs must be greater than ΔσFL. The study is based on a simple continuum mechanics approach and its purpose is the investigation of the suitability of both ΔK and Δσs to characterise the crack driving force that activates complex fracture processes at the microstructure's scale. The investigation pertains to conditions that lead to the ultimate failure of the component at values of Δσs > ΔσFL.
FRONT DEVELOPMENT OF A LONG FATIGUE CRACK DURING ITS GROWTH
Authors: Hammouda M. M. I. , Seleem M. H. , Sallam H. E. M. , Ahmad S. S. E.
Published: February 2008

Abstract— A 3‐D elastic‐plastic finite element analysis has been developed to simulate the deformation development along the front of a long mode I single edge crack in plates subjected to either monotonic or cyclic loading. Idealisations having both equal and unequal layers through the thickness of the plate were involved. Plane stress and plane strain 2‐D finite element analyses were also performed and compared with the present 3‐D solutions. The development of the monotonic and cyclic crack tip plastically deformed zones and opening displacements were traced and correlated to accommodate the effect of the plate thickness and the profile of the crack front. A previously developed crack tip deformation parameter was invoked to predict the effect of the specimen thickness on mode I fatigue crack growth and the associated change of crack front profile. Comparison of such a prediction and the experimental findings of the present work reflected the capability of that parameter in modelling fatigue crack growth through the plate thickness.
ASSISTED CRACK GROWTH IN MARAGING STEEL WELDS BY GASEOUS HYDROGEN
Authors: Tsay L. W. , Huang W. B. , Chen C.
Published: February 2008

Abstract— The effects of environmental hydrogen content on fatigue crack growth rates (FCGRs) in T‐250 maraging steel plates and laser welds were investigated. The influence of ageing treatments on fatigue characteristics of the alloy was also studied. Experimental results revealed that the accelerated FCGRs in the presence of hydrogen were always associated with changes in fracture modes that appear in compact‐tension specimens. Even for overaged specimens with excellent resistance to gaseous hydrogen embrittlement, such an acceleration of crack growth in hydrogen could not be avoided. The crack path of underaged specimens in hydrogen was found mainly along prior austenite boundaries for steel plates and along coarse columnar boundaries for welds. In gaseous hydrogen, peak‐aged welds exhibited intergranular and quasi‐cleavage mixed fracture modes, compared to mainly quasi‐clevage for similar aged steel plates. Hence, the enhancement of crack growth in hydrogen was more pronounced for the welds. Overaged welds showed higher FCGRs than the same aged steel plates only in hydrogen and for ΔK values greater than 20MPa√m.
Technology education students: e‐tutors for school children
Authors: Johnson Genevieve Marie , Bratt Sharon E.
Published: February 2008

E‐tutoring refers to individualised learning support mediated by Internet technology. While increased demand for tutors has led to a surge in commercial e‐tutoring services, volunteer e‐tutoring programs for children are rare. To test the viability of volunteer e‐tutoring for elementary school students, 10 undergraduate students enrolled in a technology education (TE) course provided online with instructional support to children in need of tutoring services. Each e‐tutor was assigned a specific child, developed a Web Course Tools course and corresponding online activities to improve teacher‐identified skill deficiencies, and provided 8 weeks of e‐tutoring. Three video conferences complemented online instructional interaction between e‐tutor and e‐tutee. Children, parents and TE students expressed positive evaluation of the initiative.
The Implementation of European Anti‐Discrimination Directives: Converging towards a Common Model?
Authors: BELL MARK
Published: February 2008

This article examines the impact on national law and policy of two Directives on combating discrimination adopted by the EU in 2000. It considers the extent to which their transposition has resulted in the ‘Europeanisation’ of anti‐discrimination law and whether this implies convergence in the direction of a common model. Two themes are examined: the list of protected grounds of discrimination and the creation of equality institutions. All 27 states have introduced legal reforms in response to the Directives and a loose level of convergence can be identified. Nevertheless, specific national traditions have proved resilient, for example, shaping the meaning attached to terms such as ‘disability’ or the structure and powers of equality bodies.
2. IN DEFENSE OF PROVINCIALIZING EUROPE: A RESPONSE TO CAROLA DIETZE
Authors: CHAKRABARTY DIPESH
Published: February 2008

This response to Carola Dietze's critique of Provincializing Europe takes up for examination three key expressions or ideas on which the original argument of the book was founded: hyperreal Europe, historicism, and political modernity. I appreciate the spirit of Dietze's engagement with the book, but I show that her critique is based on a degree of misapprehension of these three central ideas. While clarifying the details and the degree of my disagreement with Dietze, I provide my own critique of Dietze's proposal of “equal histories” by arguing that Dietze has not named or explained the unit with respect to which different histories could be considered equal. I also argue that Dietze's proposals about judging societies only by their “own” standards, and basing human dignity on the idea of a “human nature” that could be seen as a “constant,” do not solve the problems she sees with my book and are themselves open to some serious historical and logical criticism.
Comparison of Hemolytic Properties of Different Shapes of Occlusion of Blood Sac in Occlusive‐type Pulsatile Blood Pump
Authors: Choi Hyuk , Min Byoung Goo , Won Yong Soon
Published: February 2008

Abstract:  The occlusive‐type pulsatile extracorporeal blood pump (T‐PLS, Seoul National University, Seoul, Korea) received the Communauté Européenne mark of the European Directives (2003) and Korea Food and Drug Administration approval (2004) for short‐term application as an extracorporeal life support system. The pump system was recently upgraded in the ameliorated actuator head for reducing hemolysis, rather than in the existing actuator head. In this study, the hemolytic performance of the new pump system (assessed as the degree of occlusiveness of the blood sac) was compared with the existing one. A roller pump, the Stockert S3 (Stockert Instrumente GmbH, Munchen, Germany), was selected as a control device. Five tests were conducted for each pump, with each of these tests lasting for 6 h. A pump flow of 3 L/min with 50 beats per minute was included in the hemolytic test conditions. The lowest hemolytic results were obtained by the new pump system yielding a normalized index of hemolysis of less than 0.005 g/100 L, and this result was one‐fourth that of the roller pump, Stockert S3.
ICD Monitoring Zones: Intricacies, Pitfalls, and Programming Tips
Authors: MANSOUR FADI , KHAIRY PAUL
Published: February 2008

Implantable cardioverter‐defibrillators (ICD) are widely regarded as the treatment of choice for primary and secondary prevention against sudden cardiac death across a broad spectrum of underlying pathologies. Over the past 20 years, ICDs have evolved into complex multifunctional units capable of recording, chronicling, self‐testing, and delivering interventional therapies. Technological advances permitted the creation of ICD monitoring zones that are now considered valuable in diagnosing slower, presumably more stable ventricular arrhythmias. They may be helpful especially in patients with unexplained symptoms such as palpitations and/or syncope, particularly in the setting of antiarrhythmic pharmacological therapy that may slow ventricular tachyarrhythmias. Caregivers largely view ICD monitoring zones as passive features that do not interfere or interact with appropriate functioning of active treatment zones. As will be discussed in this clinical review, this is not always the case. Herein, we unravel the intricacies regarding monitoring zone functions and algorithms, highlight potential pitfalls, and offer practical programming tips relevant to each device manufacturer.
Down‐regulation of osteopontin attenuates breast tumour progression in vivo
Authors: Chakraborty Goutam , Jain Shalini , Patil Tushar V. , Kundu Gopal C.
Published: February 2008

Development of breast tumour malignancies results in enhanced expression of various oncogenic molecules. Elevated expression of osteopontin (OPN) in higher grades of breast carcinoma correlates with enhanced expressions of several oncogenic molecules (urokinase‐type plasminogen activator [uPA], matrix metalloproteinase‐2/‐9 [MMP‐2 and ‐9]) and increased angiogenic potential of breast carcinoma. In this study, using in vitro and multiple in vivo models, we have demonstrated that silencing of OPN by its specific small interfering RNA (siRNA) down‐regulates the expressions of oncogenic molecules such as uPA, MMP‐2 and ‐9 resulting in inhibition of in vitro cell motility and in vivo tumourigenicity in mice. Moreover our results demonstrated that OPN−/− mice showed slower progression of tumour growth in breast cancer model as compared to wild‐type mice. Furthermore, the data showed that injection of carcinogenic compound, pristane (2, 6,10,14‐tetramethylpen‐tadecane) induces breast tumour progression leading to enhanced expression of OPN and other oncogenic molecules in mammary fat pad of nude‐ and wild‐type mice but not in OPN−/ mice. However, intratumoural injection of OPN siRNA to pristane‐induced tumour significantly suppressed these effects. Our data revealed that knocking down of OPN effectively curb breast cancer progression and further suggested that developing of OPN‐based therapeutics might be an emerging approach for the next generation of breast cancer management.
OBSERVATIONS ON ULTRAVIOLET ERYTHEMA*
Authors: van der Leun J. C.
Published: February 2008

Abstract— Ultraviolet erythemas elicited on human skin with 250 nm‐ and 300 nm‐radiation have been compared. Two features have been investigated: the lateral extension of the erythema beyond the boundaries of the exposed skin area, and the skin temperature associated with the erythema. In both respects, marked differences have been found between the two types of erythema.
SUPPRESSION OF PHAGE T4 BY CO‐INFECTION WITH U.V.‐INACTIVATED HOMOLOGOUS PHAGE
Authors: Harm Walter
Published: February 2008

Abstract— Unirradiated phage T4v1 may fail to produce viable progeny in cells which are co‐infected with u.v.‐irradiated homologous particles. The extent of this effect, called suppression, is positively correlated with the multiplicity of infection of the irradiated phage and with the U.V. dose. The suppression reaches a maximum level at about 30–600 lethal hits. Quantitative evaluation of the results shows that in some complexes one irradiated phage particle is sufficient to suppress an unirradiated phage. Two hypotheses are discussed to explain the results. (a) Lethal u.v.‐damages are incorporated into the unirradiated phage genome by genetic recombination; (b) Genetic subunits (e.g. cistrons or operons) of the u.v.‐irradiated phages produce informationally incorrect messenger RNA molecules, which compete with the correct ones from the unirradiated phage in the protein‐synthetizing system. Hypothesis (6) appears to be more adequate to explain the experimental results.
HOST‐CELL REACTIVATION OF NON‐LETHAL ULTRAVIOLET‐EFFECTS
Authors: Harm Walter
Published: February 2008

Abstract— Delay of intracellular growth of u.v.‐irradiated bacteriophage T1 and Λ was compared in host‐cell reactivating [HCR(+)] and non‐host‐cell reactivating [HCR(—)] bacterial strains. At a given phage survival level, intracellular growth delay occurs to the same extent in HCR (+) and HCR (‐) strains; at a given absolute u.v.‐dose, this delay is considerably more expressed in HCR (‐) than in HCR (+) strains. Therefore, it does not reflect the time required for the HCR repair of otherwise lethal U.V. lesions. The results rather suggest that U.V. causes, besides lethal lesions, stable photoproducts in the DNA, which are a priori non‐lethal, and which are recognized and efficiently eliminated by the HCR repair system. The HCR enzymes likewise act on (non‐lethal) u.v.‐photoproducts causing prophage induction in lysogenic cells. Consequently, one obtains the maximum induction effect in a lysogenic HCR (‐) strain at a much lower u.v.‐dose than in the corresponding lysogenic HCR (+) strain. In contrast, u.v.‐damage causing loss of the host cell's capacity to support growth of unirradiated phage is not affected by HCR.
Multiple-Locus Variable-Number Tandem-Repeat Analysis as a Tool for Subtyping
Listeria monocytogenes
Strains
Authors: Sperry Katharine E. Volpe , Kathariou Sophia , Edwards Justin S. , Wolf Leslie A.
Published: February 2008

Listeria monocytogenes
, like many other food-borne bacteria, has certain strains that are commonly linked to outbreaks. Due to the relatively low numbers of affected individuals, outbreaks of
L. monocytogenes
can be difficult to detect. The current technique of molecular subtyping in PulseNet laboratories to identify genetically similar strains is pulsed-field gel electrophoresis (PFGE). While PFGE is state-of-the-art, interlaboratory comparisons are difficult because the results are highly susceptible to discrepancies due to even minor variations in experimental conditions and the subjectivity of band marking. This research was aimed at the development of a multiple-locus variable-number tandem-repeat analysis (MLVA) that can be implemented in PulseNet laboratories to replace or complement existing protocols. MLVA has proven to be a rapid and highly discriminatory tool for subtyping many bacteria. In this study, a novel MLVA method for
L. monocytogenes
strains was developed utilizing eight loci multiplexed into two PCRs. The PCR products were separated by capillary gel electrophoresis for high throughput and accurate sizing, and the fragment sizes were analyzed and clustered based on the number of repeats. When tested against a panel of 193 epidemiologically linked and nonlinked isolates, this MLVA for
L. monocytogenes
strains demonstrates strong epidemiological concordance. Since MLVA is a high-throughput screening method that is fairly inexpensive, easy to perform, rapid, and reliable, it is well suited to interlaboratory comparisons during epidemiological investigations of food-borne illness.
Tree-ring-based growth analysis for a sugar maple stand: relations to local climate and transient soil properties
Authors: Yin Xiwei , Foster Neil W. , Morrison Ian K. , Arp Paul A.
Published: February 2008

Tree-ring-based growth analysis often suffers from lack of concurrent climate and soil data. This study used (i) regressions to adjust weather records for local conditions, (ii) climate-driven simulation models to simulate soil moisture and temperatures, and (iii) site-specific regression models to reconstruct ion concentrations in soil solution for the past 40 years. A standardized tree-ring index was used to measure tree radial growth. The study site was a sugar maple (Acersaccharum Marsh.) dominated deciduous stand in Ontario (Turkey Lakes). Based on reconstructed data, when only climate factors were used, 63% of the year-to-year variation in growth index was explained by (i) precipitation during the growing season, and (ii) air temperatures in midwinter, during the growing season, and prior to autumnal leaf fall. The proportion of explained variance was raised to 83% when (i) precipitation was replaced with soil water content, and (ii) soil solution nitrate concentrations in August and in the preceding recuperating season were incorporated. Hence, introducing transient soil properties into tree-ring based growth analysis may substantially reduce error variance; climatic effects on tree growth depend largely on specific, season-dependent responses of transient soil properties.
Genetic structure and variability in Pinusstrobus in Quebec
Authors: Beaulieu J. , Simon J.-P.
Published: February 2008

The level of genetic diversity of natural populations of eastern white pine (Pinusstrobus L.) from Quebec was estimated from allozyme variants of 18 loci coding 12 enzyme systems. On average, a white pine population was polymorphic at 50.6% of loci, had 1.96 alleles and 1.22 effective alleles per locus, and observed and expected heterozygosities of 0.176 and 0.180, respectively. The level of genetic diversity was lower in the populations of the St. Lawrence lowlands than in those of western Quebec. This observation will help in guiding the selection program of the eastern white pine improvement program under way in Quebec. Genetic differentiation among sampled populations was weak and accounted for only 2% of the total diversity. The estimate of gene flow was very high, resulting in low values for genetic distances among populations. Only one locus showed a heterogeneity of allelic frequencies among populations after the Bonferroni procedure was applied for simultaneous statistical tests. A cluster analysis based on genetic distances among populations revealed that the Anticosti and Abitibi populations, located at the limit of the natural range of white pine, were similar to populations from regions that were geographically the most distant.
Gene Ontology-driven transcriptional analysis of CD34+cell-initiated megakaryocytic cultures identifies new transcriptional regulators of megakaryopoiesis
Authors: Fuhrken Peter G. , Chen Chi , Apostolidis Pani A. , Wang Min , Miller William M. , Papoutsakis Eleftherios T.
Published: February 2008

Differentiation of hematopoietic stem and progenitor cells is an intricate process controlled in large part at the level of transcription. While some key megakaryocytic transcription factors have been identified, the complete network of megakaryocytic transcriptional control is poorly understood. Using global gene expression microarray analysis, Gene Ontology-based functional annotations, and a novel interlineage comparison with parallel, isogenic granulocytic cultures as a negative control, we closely examined the mRNA level of transcriptional regulators in megakaryocytes derived from human mobilized peripheral blood CD34+hematopoietic cells. This approach identified 199 differentially expressed transcription factors or transcriptional regulators. We identified and detailed the transcriptional kinetics of most known megakaryocytic transcription factors including GATA1, FLI1, and MAFG. Furthermore, many genes with transcription factor activity or transcription factor binding activity were identified in megakaryocytes that had not previously been associated with that lineage, including BTEB1, NR4A2, FOXO1A, MEF2C, HDAC5, VDR, and several genes associated with the tumor suppressor p53 (HIPK2, FHL2, and TADA3L). Protein expression and nuclear localization were confirmed in megakaryocytic cells for four of the novel candidate megakaryocytic transcription factors: FHL2, MXD1, E2F3, and RFX5. In light of the hypothesis that transcription factors expressed in a particular differentiation program are important contributors to such a program, these data substantially expand our understanding of transcriptional regulation in megakaryocytic differentiation of stem and progenitor cells.
Muscarinic signaling influences the patterning and phenotype of cholinergic amacrine cells in the developing chick retina
Authors: Stanke Jennifer J , Lehman Bret , Fischer Andy J
Published: February 2008

Background

Many studies in the vertebrate retina have characterized the differentiation of amacrine cells as a homogenous class of neurons, but little is known about the genes and factors that regulate the development of distinct types of amacrine cells. Accordingly, the purpose of this study was to characterize the development of the cholinergic amacrine cells and identify factors that influence their development. Cholinergic amacrine cells in the embryonic chick retina were identified by using antibodies to choline acetyltransferase (ChAT).

Results

We found that as ChAT-immunoreactive cells differentiate they expressed the homeodomain transcription factors Pax6 and Islet1, and the cell-cycle inhibitor p27kip1. As differentiation proceeds, type-II cholinergic cells, displaced to the ganglion cell layer, transiently expressed high levels of cellular retinoic acid binding protein (CRABP) and neurofilament, while type-I cells in the inner nuclear layer did not. Although there is a 1:1 ratio of type-I to type-II cells in vivo, in dissociated cell cultures the type-I cells (ChAT-positive and CRABP-negative) out-numbered the type-II cells (ChAT and CRABP-positive cells) by 2:1. The relative abundance of type-I to type-II cells was not influenced by Sonic Hedgehog (Shh), but was affected by compounds that act at muscarinic acetylcholine receptors. In addition, the abundance and mosaic patterning of type-II cholinergic amacrine cells is disrupted by interfering with muscarinic signaling.

Conclusion

We conclude that: (1) during development type-I and type-II cholinergic amacrine cells are not homotypic, (2) the phenotypic differences between these subtypes of cells is controlled by the local microenvironment, and (3) appropriate levels of muscarinic signaling between the cholinergic amacrine cells are required for proper mosaic patterning.
Copeptin, a novel prognostic biomarker in ventilator-associated pneumonia
Authors: Seligman Renato , Papassotiriou Jana , Morgenthaler Nils G , Meisner Michael , Teixeira Paulo JZ
Published: February 2008

Background

The present study sought to investigate the correlation of copeptin with the severity of septic status in patients with ventilator-associated pneumonia (VAP), and to analyze the usefulness of copeptin as a predictor of mortality in VAP.

Methods

The prospective observational cohort study was conducted in a teaching hospital. The subjects were 71 patients consecutively admitted to the intensive care unit from October 2003 to August 2005 who developed VAP. Copeptin levels were determined on day 0 and day 4 of VAP. Patients were followed for 28 days after the diagnosis, when they were considered survivors. Patients who died before day 28 were classified as nonsurvivors. There were no interventions.

Results

Copeptin levels increased from sepsis to severe sepsis and septic shock both on day 0 and day 4 (P = 0.001 and P = 0.009, respectively). Variables included in the univariable logistic regression analysis for mortality were age, gender, Acute Physiology and Chronic Health Evaluation II score and ln copeptin on day 0 and day 4. Mortality was directly related to ln copeptin levels on day 0 and day 4, with odds ratios of 2.32 (95% confidence interval, 1.25 to 4.29) and 2.31 (95% confidence interval, 1.25 to 4.25), respectively. In a multivariable logistic regression model for mortality, only ln copeptin on day 0 with odds ratio 1.97 (95% confidence interval, 1.06 to 3.69) and ln copeptin on day 4 with odds ratio 2.39 (95% confidence interval, 1.24 to 4.62) remained significant.

Conclusion

Our data demonstrate that copeptin levels increase progressively with the severity of sepsis and are independent predictors of mortality in VAP.
Bovine prolactin-related protein-I is anchored to the extracellular matrix through interactions with type IV collagen
Authors: Takahashi Toru , Yamada Osamu , Soares Michael J , Hashizume Kazuyoshi
Published: February 2008

The bovine placenta produces an array of proteins structurally similar to pituitary prolactin (PRL). At least ten genes of the bovine placental PRL family, including bovine placental lactogen (bPL) and ten bovine PRL-related protein-I to -X (bPRP-I to -X), encode hormones/cytokines predicted to be involved in the establishment and maintenance of pregnancy. Targets and biological roles for most members of the bovine PRL family have yet to be specified. This study focused on three members of bovine PRL family, bPL, bPRP-I, and bPRP-VI. An alkaline phosphatase (AP) tagging strategy was used to monitor interactions of the ligands with their targets. AP-bPRP-I and AP-bPRP-VI specifically bound to tissue sections of the bovine placentome. AP-bPRP-I and AP-bPRP-VI binding within the placentome mimicked the distribution of the extracellular matrix (ECM). Consequently, AP fusion protein binding to individual ECM components (heparin, laminin, fibronectin, type I collagen, and type IV collagen) was evaluated. AP-bPRP-I specifically bound to type IV collagen, but not to the other ECM components. AP-bPRP-VI exhibited weak interactions with ECM components, while AP-bPL and AP did not show significant binding to any of the ECM components. Binding of AP-bPRP-I to type IV collagen was concentration-dependent, influenced by salt concentrations, and specific to the N-terminal cross-linking domain (7S) of type IV collagen but not its triple-helical domain. The interaction of bPRP-I with type IV collagen suggests that bPRP-I accumulates in the ECM where it likely acts on cells traversing the bovine placentome.
Quantitative Trait Analysis of Type 2 Diabetes Susceptibility Loci Identified From Whole Genome Association Studies in the Insulin Resistance Atherosclerosis Family Study
Authors: Palmer Nicholette D. , Goodarzi Mark O. , Langefeld Carl D. , Ziegler Julie , Norris Jill M. , Haffner Steven M. , Bryer-Ash Michael , Bergman Richard N. , Wagenknecht Lynne E. , Taylor Kent D. , Rotter Jerome I. , Bowden Donald W.
Published: February 2008

OBJECTIVE—Evaluate type 2 diabetes susceptibility variants identified from genome-wide association studies in Hispanic Americans and African Americans from the Insulin Resistance Atherosclerosis Family Study (IRAS-FS) for association with quantitative measures of glucose homeostasis and determine their biological role in vivo.

RESEARCH DESIGN AND METHODS—Seventeen type 2 diabetes–associated single nucleotide polymorphisms (SNPs) were genotyped in 1,268 Hispanic- and 581 African-American participants from the IRAS-FS. SNPs were tested for association with quantitative measures of glucose homeostasis, including insulin sensitivity index (SI), acute insulin response (AIR), and disposition index.

RESULTS—Previously identified risk variants in cyclin-dependent kinase 5 regulatory subunit associated protein 1-like 1 (CDKAL1) were associated with reduced AIR (P < 0.0046) in Hispanic Americans. Additionally in Hispanic Americans, the variant in a hypothetical gene (chromosome 11; LOC387761) was significantly associated with AIR (P = 0.0046) with the risk allele showing protective effects, i.e., increased AIR. In both Hispanic- and African-American populations, risk variants at the solute carrier family 30, member 8 (SLC30A8) locus were nominally associated with decreased disposition index (P < 0.078). Risk variants in the insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) locus were associated with a decreased disposition index (P = 0.011) exclusively in Hispanic Americans.

CONCLUSIONS—These data indicate a distinct, limited number of diabetes-related genes, more specifically the SNPs in the genes identified in European-derived populations, with modest evidence for association with glucose homeostasis traits in Hispanic Americans and African Americans. We observe evidence that diabetes risk for CDKAL1, SLC30A8, IGF2BP2, and LOC387761 is specifically mediated through defects in insulin secretion. The mechanisms of other predisposing genes remain to be elucidated.
Serum FGF21 Levels Are Increased in Obesity and Are Independently Associated With the Metabolic Syndrome in Humans
Authors: Zhang Xinmei , Yeung Dennis C.Y. , Karpisek Michal , Stejskal David , Zhou Zhi-Guang , Liu Feng , Wong Rachel L.C. , Chow Wing-Sun , Tso Annette W.K. , Lam Karen S.L. , Xu Aimin
Published: February 2008

OBJECTIVE— Fibroblast growth factor 21 (FGF21) is a metabolic regulator with multiple beneficial effects on glucose homeostasis and insulin sensitivity in animal models. This study aimed to investigate the relationship between its serum levels and various cardiometabolic parameters in humans.

RESEARCH DESIGN AND METHODS— A newly developed immunoassay was used to measure serum FGF21 levels in 232 Chinese subjects recruited from our previous cross-sectional studies. The mRNA expression levels of FGF21 in the liver and adipose tissues were quantified by real-time PCR.

RESULTS— Serum FGF21 levels in overweight/obese subjects were significantly higher than in lean individuals. Serum FGF21 correlated positively with adiposity, fasting insulin, and triglycerides but negatively with HDL cholesterol, after adjusting for age and BMI. Logistic regression analysis demonstrated an independent association between serum FGF21 and the metabolic syndrome. Furthermore, the increased risk of the metabolic syndrome associated with high serum FGF21 was over and above the effects of individual components of the metabolic syndrome. Our in vitro study detected a differentiation-dependent expression of FGF21 in 3T3-L1 adipocytes and human adipocytes. In db/db obese mice, FGF21 mRNA expression was markedly increased in both the liver and adipose tissue compared with that in their lean littermates. Furthermore, FGF21 expression in subcutaneous fat correlated well with its circulating concentrations in humans.

CONCLUSIONS— FGF21 is a novel adipokine associated with obesity-related metabolic complications in humans. The paradoxical increase of serum FGF21 in obese individuals, which may be explained by a compensatory response or resistance to FGF21, warrants further investigation.
Expanded clinical spectrum of spondylocarpotarsal synostosis syndrome and possible manifestation in a heterozygous father
Authors: Mitter Diana , Krakow Deborah , Farrington‐Rock Claire , Meinecke Peter
Published: February 2008

We report on a 5‐year‐old boy with spondylocarpotarsal synostosis (SCT) syndrome who presents with disproportionate short stature, thoracic scoliosis, pes planus, dental enamel hypoplasia, unilateral conductive hearing loss and mild facial dysmorphisms. Radiographs showed abnormal segmentation of the spine with block vertebrae and carpal synostosis. In addition to the typical phenotype of SCT syndrome, he showed pronounced delay of carpal bone age and bilateral epiphyseal dysplasia of the proximal femora. The patient's father has mild short stature and unilateral hip dysplasia. Molecular studies of the filamin B gene (FLNB) revealed a homozygous mutation in the index patient while both parents were heterozygous for the mutation. In this report we expand the phenotype of SCT syndrome in a patient with a causal FLNB mutation. © 2008 Wiley‐Liss, Inc.
Determination of levonorgestrel in human plasma by liquid chromatography–tandem mass spectrometry method: application to a bioequivalence study of two formulations in healthy volunteers
Authors: Zhao Li‐Zi , Zhong Guo‐Ping , Bi Hui‐Chang , Ding Liang , Deng Ying , Guan Su , Chen Xiao , Huang Zhi‐ying , Huang Min
Published: February 2008

A rapid and sensitive liquid chromatography–tandem mass spectrometry (LC/MS/MS) method to determine levonorgestrel in human plasma was developed and fully validated. After hexane–ethyl acetate (70:30, v/v) induced extraction from the plasma samples, levonorgestrel was subjected to LC/MS/MS analysis using electro‐spray ionization. The MS system was operated in the selected reaction monitoring mode. Chromatographic separation was performed on a Hypersil BDS C18 column (i.d. 2.1 × 50 mm, particle size 3 µm). The method had a chromatographic running time of 2.0 min and linear calibration curves over the concentration ranges of 0.25–90 ng/mL for levonorgestrel. The lower limit of quantification of the method was 0.25 ng/mL for levonorgestrel. The intra‐ and inter‐batch precision was 3.7–10.2 and 5.1–12.9%, respectively, for all quality control samples at concentrations of 0.5, 6.0 and 45.0 ng/mL. These results indicate that the method was efficient with a simple preparation procedure and a very short running time (2.0 min) for levonorgestrel compared with those methods reported in the literature and had high selectivity, acceptable accuracy, precision and sensitivity. The validated LC/MS/MS method was successfully used for a bioequivalence study of two tablet formulations of levonorgestrel in healthy volunteers. Copyright © 2008 John Wiley & Sons, Ltd.
LC‐MS determination and pharmacokinetic studies of paeonol in rat plasma after administration of different compatibility of Su‐Xiao‐Xin‐Tong prescriptions
Authors: Xiao Yao , Zhang Ying‐hao , Sheng Yu‐xin , Zhang Jin‐lan
Published: February 2008

A rapid and specific liquid chromatographic/electrospray ionization mass spectrometric (LC/ESI–MS) method has been developed and validated for the identification and quantification of paeonol in rat plasma. Paeonol and internal standard were isolated from plasma samples by liquid–liquid extraction with chloroform. The chromatographic separation was accomplished on a Zorbax‐SB C18 column (100 × 2.1 mm, 3.5 µm). The mobile phase consisted of acetonitrile and 0.1% aqueous formic acid (64:36) was delivered at a flow rate of 0.2 mL/min. Detection was performed on a single quadrupole mass spectrometer by selected ion monitoring mode via electrospray ionization source. Linearity was established for the range of concentrations 0.0525–15.8 µg/mL with a coefficient correlation (r) of 0.9995. The intra‐ and inter‐day precision (RSD%) was lower than 9.34% and accuracy ranged from 93.7 to 102.3%. The lower limit of quantification was 0.0525 µg/mL. The proposed method was used to determine the concentration of paeonol for pharmacokinetic studies. The pharmacokinetics of different compatibility prescriptions of Su‐Xiao‐Xin‐Tong were studied and compared. Copyright © 2008 John Wiley & Sons, Ltd.
Development and validation of a sensitive LC‐MS/MS method with electrospray ionization for quantitation of rhein in human plasma: application to a pharmacokinetic study
Authors: Layek Buddhadev , Kumar T. Santosh , Trivedi Ravi Kumar , Mullangi Ramesh , Srinivas Nuggehally R.
Published: February 2008

A highly sensitive and specific LC‐MS/MS method has been developed and validated for the estimation of rhein with 100 µL human plasma using celecoxib as an internal standard (IS). The API‐4000 Q‐Trap LC‐MS/MS was operated under multiple reaction‐monitoring mode using the electrospray ionization technique. The assay procedure involved extraction of rhein and IS from human plasma with acetonitrile, which yielded consistent recoveries of 36.01 and 65.85% for rhein and IS, respectively. The total chromatographic run time was 5.0 min and the elution of rhein and IS occurred at ∼1.60 and 3.96 min, respectively. The resolution of peaks was achieved with 0.01 m ammonium acetate (pH 6.0):acetonitrile:methanol (30:58:12, v/v) on an Inertsil ODS‐3 column. The method was proved to be accurate and precise at a linearity range of 0.005–5.00 µg/mL with a correlation coefficient (r) of ≥0.995. The lower limit of quantitation was 0.005 µg/mL. The intra‐ and inter‐day precision and accuracy values were found to be within the assay variability limits as per the FDA guidelines. Rhein was found to be stable in the battery of stability studies. The application of the assay to pre‐clinical pharmacokinetic studies confirmed the utility of the assay to derive pharmacokinetic parameters. Copyright © 2008 John Wiley & Sons, Ltd.