bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design considerations in a sib-pair study of linkage for susceptibility loci in cancer
Authors: Kerber Richard A , Amos Christopher I , Yeap Beow Y , Finkelstein Dianne M , Thomas Duncan C 
Published: July 2008

AbstractBackgroundModern approaches to identifying new genes associated with disease allow very fine analysis of associaton and can be performed in population based case-control studies. However, the sibpair design is still valuable because it requires few assumptions other than acceptably high penetrance to identify genetic loci.MethodsWe conducted simulation studies to assess the impact of design factors on relative efficiency for a linkage study of colorectal cancer. We considered two test statistics, one comparing the mean IBD probability in affected pairs to its null value of 0.5, and one comparing the mean IBD probabilities between affected and discordant pairs. We varied numbers of parents available, numbers of affected and unaffected siblings, reconstructing the genotype of an unavailable affected sibling by a spouse and offspring, and elimination of sibships where the proband carries a mutation at another locus.ResultsPower and efficiency were most affected by the number of affected sibs, the number of sib pairs genotyped, and the risk attributable to linked and unlinked loci. Genotyping unaffected siblings added little power for low penetrance models, but improved validity of tests when there was genetic heterogeneity and for multipoint testing. The efficiency of the concordant-only test was nearly always better than the concordant-discordant test. Replacement of an unavailable affected sibling by a spouse and offspring recovered some linkage information, particularly if several offspring were available. In multipoint analysis, the concordant-only test was showed a small anticonservative bias at 5 cM, while the multipoint concordant-discordant test was generally the most powerful test, and was not biased away from the null at 5 cM.ConclusionGenotyping parents and unaffected siblings is useful for detecting genotyping errors and if allele frequencies are uncertain. If adequate allele frequency data are available, we suggest a single-point affecteds-only analysis for an initial scan, followed by a multipoint analysis of affected and unaffected members of all available sibships with additional markers around initial hits.
Male silver eels mature by swimming
Authors: Palstra Arjan P , Schnabel Denhi , Nieveen Maaike C , Spaink Herman P , van den Thillart Guido EEJM 
Published: July 2008

Abstract

Background
If European silver eels are prevented from reproductive migration, they remain in a prepubertal stage by dopaminergic inhibition of pituitary activity. Because this inhibition is likely a requirement for an extended female growth stage, we tested if it is sex-specific by subjecting both sexes to stimulation by GnRHa (Gonadotropin-Releasing Hormone agonist) – injection or 3-months swimming in seawater.

Results
In contrast to females, males showed a two- to three-fold higher LHβ (luteinising hormone β subunit) – expression, a three- to five-fold higher GSI (Gonadosomatic index) and induced spermatogenesis when compared with the untreated control group.

Conclusion
Dopaminergic inhibition is thus not effective in males and swimming results in natural maturation, probably via GnRH-release.
Tiling array-CGH for the assessment of genomic similarities among synchronous unilateral and bilateral invasive breast cancer tumor pairs
Authors: Brommesson Sara , Jönsson Göran , Strand Carina , Grabau Dorthe , Malmström Per , Ringnér Markus , Fernö Mårten , Hedenfalk Ingrid 
Published: July 2008

Abstract

Background
Today, no objective criteria exist to differentiate between individual primary tumors and intra- or intermammary dissemination respectively, in patients diagnosed with two or more synchronous breast cancers. To elucidate whether these tumors most likely arise through clonal expansion, or whether they represent individual primary tumors is of tumor biological interest and may have clinical implications. In this respect, high resolution genomic profiling may provide a more reliable approach than conventional histopathological and tumor biological factors.

Methods
32 K tiling microarray-based comparative genomic hybridization (aCGH) was used to explore the genomic similarities among synchronous unilateral and bilateral invasive breast cancer tumor pairs, and was compared with histopathological and tumor biological parameters.

Results
Based on global copy number profiles and unsupervised hierarchical clustering, five of ten (p = 1.9 × 10-5) unilateral tumor pairs displayed similar genomic profiles within the pair, while only one of eight bilateral tumor pairs (p = 0.29) displayed pair-wise genomic similarities. DNA index, histological type and presence of vessel invasion correlated with the genomic analyses.

Conclusion
Synchronous unilateral tumor pairs are often genomically similar, while synchronous bilateral tumors most often represent individual primary tumors. However, two independent unilateral primary tumors can develop synchronously and contralateral tumor spread can occur. The presence of an intraductal component is not informative when establishing the independence of two tumors, while vessel invasion, the presence of which was found in clustering tumor pairs but not in tumor pairs that did not cluster together, supports the clustering outcome. Our data suggest that genomically similar unilateral tumor pairs may represent a more aggressive disease that requires the addition of more severe treatment modalities, and underscores the importance of evaluating the clonality of multiple tumors for optimal patient management. In summary, our findings demonstrate the importance of evaluating the properties of both tumors in order to determine the most optimal patient management.
Soluble histone H2AX is induced by DNA replication stress and sensitizes cells to undergo apoptosis
Authors: Liu Ying , Parry Joshua A , Chin Anna , Duensing Stefan , Duensing Anette 
Published: July 2008

Abstract

Background
Chromatin-associated histone H2AX is a key regulator of the cellular responses to DNA damage. However, non-nucleosomal functions of histone H2AX are poorly characterized. We have recently shown that soluble H2AX can trigger apoptosis but the mechanisms leading to non-chromatin-associated H2AX are unclear. Here, we tested whether stalling of DNA replication, a common event in cancer cells and the underlying mechanism of various chemotherapeutic agents, can trigger increased soluble H2AX.

Results
Transient overexpression of H2AX was found to lead to a detectable fraction of soluble H2AX and was associated with increased apoptosis. This effect was enhanced by the induction of DNA replication stress using the DNA polymerase α inhibitor aphidicolin. Cells manipulated to stably express H2AX did not contain soluble H2AX, however, short-term treatment with aphidicolin (1 h) resulted in detectable amounts of H2AX in the soluble nuclear fraction and enhanced apoptosis. Similarly, soluble endogenous H2AX was detected under these conditions. We found that excessive soluble H2AX causes chromatin aggregation and inhibition of ongoing gene transcription as evidenced by the redistribution and/or loss of active RNA polymerase II as well as the transcriptional co-activators CBP and p300.

Conclusion
Taken together, these results show that DNA replication stress rapidly leads to increased soluble H2AX and that non-chromatin-associated H2AX can sensitize cells to undergo apoptosis. Our findings encourage further studies to explore H2AX and the cellular pathways that control its expression as anti-cancer drug targets.
Development of the Knee Quality of Life (KQoL-26) 26-item questionnaire: data quality, reliability, validity and responsiveness
Authors: Garratt Andrew M , Brealey Stephen , Robling Michael , Atwell Chris , Russell Ian , Gillespie William , King David ,   the DAMASK Trial Team
Published: July 2008

AbstractBackgroundThis article describes the development and validation of a self-reported questionnaire, the KQoL-26, that is based on the views of patients with a suspected ligamentous or meniscal injury of the knee that assesses the impact of their knee problem on the quality of their lives.MethodsPatient interviews and focus groups were used to derive questionnaire content. The instrument was assessed for data quality, reliability, validity, and responsiveness using data from a randomised trial and patient survey about general practitioners' use of Magnetic Resonance Imaging for patients with a suspected ligamentous or meniscal injury.ResultsInterview and focus group data produced a 40-item questionnaire designed for self-completion. 559 trial patients and 323 survey patients responded to the questionnaire. Following principal components analysis and Rasch analysis, 26 items were found to contribute to three scales of knee-related quality of life: physical functioning, activity limitations, and emotional functioning. Item-total correlations ranged from 0.60–0.82. Cronbach's alpha and test retest reliability estimates were 0.91–0.94 and 0.80–0.93 respectively. Hypothesised correlations with the Lysholm Knee Scale, EQ-5D, SF-36 and knee symptom questions were evidence for construct validity. The instrument produced highly significant change scores for 65 trial patients indicating that their knee was a little or somewhat better at six months. The new instrument had higher effect sizes (range 0.86–1.13) and responsiveness statistics (range 1.50–2.13) than the EQ-5D and SF-36.ConclusionThe KQoL-26 has good evidence for internal reliability, test-retest reliability, validity and responsiveness, and is recommended for use in randomised trials and other evaluative studies of patients with a suspected ligamentous or meniscal injury.
Validity of two physical activity questionnaires (IPAQ and PAQA) for Vietnamese adolescents in rural and urban areas
Authors: Lachat Carl K , Verstraeten Roosmarijn , Khanh Le Nguyen Bao , Hagströmer Maria , Khan Nguyen Cong , Van Nguyen Do Anh , Dung Nguyen Quang , Kolsteren Patrick W 
Published: July 2008

Abstract

Background
Although physical activity is recognised to be an important determinant of health and nutritional status, few instruments have been developed to assess physical activity in developing countries. The aim of this study was to compare the validity of the short form of the International Physical Activity Questionnaire (IPAQ) and a locally adapted version of the Physical Activity Questionnaire for Adolescents (PAQA) for use in school going adolescents in rural and urban areas in Vietnam.

Methods
Sixteen year old adolescents from rural areas (n = 137) and urban areas (n = 90) completed the questionnaires in 2006. Test-retest reliability was assessed by comparing registrations after 2 weeks. Criterion validity was assessed by comparison with 7 days continuous accelerometer logging. Validity of the two methods was assessed using Spearman correlation coefficient, intra class correlation coefficients (ICC) and Kappa statistics.

Results
Reliability of both questionnaires was poor for both the IPAQ (ICC = 0.37) and the PAQA (ICC = 0.40). Criterion validity of both questionnaires was acceptable and similar for the IPAQ (ρ = 0.21) and the PAQA (ρ = 0.27) but a significantly lower validity was observed in rural areas. Both forms poorly estimated time spent on light, moderate and vigorous physical activity. Agreement of both questionnaires to classify individuals was also low but the IPAQ performed better than the PAQA.

Conclusion
Both questionnaires have a similar and overall poor validity to be used as a population instrument in Vietnam. Low reliability and classification properties in rural areas call for further research for specific use in such settings.
Identification of genes influencing dendrite morphogenesis in developing peripheral sensory and central motor neurons
Authors: Ou Yimiao , Chwalla Barbara , Landgraf Matthias , van Meyel Donald J 
Published: July 2008

Abstract
Background
Developing neurons form dendritic trees with cell type-specific patterns of growth, branching and targeting. Dendrites of Drosophila peripheral sensory neurons have emerged as a premier genetic model, though the molecular mechanisms that underlie and regulate their morphogenesis remain incompletely understood. Still less is known about this process in central neurons and the extent to which central and peripheral dendrites share common organisational principles and molecular features. To address these issues, we have carried out two comparable gain-of-function screens for genes that influence dendrite morphologies in peripheral dendritic arborisation (da) neurons and central RP2 motor neurons.

Results
We found 35 unique loci that influenced da neuron dendrites, including five previously shown as required for da dendrite patterning. Several phenotypes were class-specific and many resembled those of known mutants, suggesting that genes identified in this study may converge with and extend known molecular pathways for dendrite development in da neurons. The second screen used a novel technique for cell-autonomous gene misexpression in RP2 motor neurons. We found 51 unique loci affecting RP2 dendrite morphology, 84% expressed in the central nervous system. The phenotypic classes from both screens demonstrate that gene misexpression can affect specific aspects of dendritic development, such as growth, branching and targeting. We demonstrate that these processes are genetically separable. Targeting phenotypes were specific to the RP2 screen, and we propose that dendrites in the central nervous system are targeted to territories defined by Cartesian co-ordinates along the antero-posterior and the medio-lateral axes of the central neuropile. Comparisons between the screens suggest that the dendrites of peripheral da and central RP2 neurons are shaped by regulatory programs that only partially overlap. We focused on one common candidate pathway controlled by the ecdysone receptor, and found that it promotes branching and growth of developing da neuron dendrites, but a role in RP2 dendrite development during embryonic and early larval stages was not apparent.

Conclusion
We identified commonalities (for example, growth and branching) and distinctions (for example, targeting and ecdysone response) in the molecular and organizational framework that underlies dendrite development of peripheral and central neurons.
The influence of body composition on therapeutic hypothermia: a prospective observational study of patients after cardiac arrest
Authors: Jimmink Joost J , Binnekade Jan M , Paulus Frederique , Mathus-Vliegen Elisebeth MH , Schultz Marcus J , Vroom Margreeth B 
Published: July 2008

Abstract
Introduction
Patients after out-of-hospital cardiac arrest (OHCA) benefit from therapeutic hypothermia for 24 hours. The time needed to reach hypothermia (target temperature of 32°C to 34°C) varies widely. In this study, we explore the relation between measures of body composition and the time needed to reach target temperature with hypothermia.

Method
We conducted a prospective observational study in patients treated with hypothermia after OHCA. Data collected included weight and height, body composition by anthropometric measures and by single-frequency body impedance, and waist-to-hip ratio. Analysis of concordance between impedance and anthropometric measures and hazard ratios of achieving target temperature (event) corrected for different body composition measures.

Results
Twenty-seven patients were included. The median (interquartile range) time to reach target temperature after admission to the intensive care unit was 191 (105 to 382) minutes. Intraclass correlation for total body fat (TBF) measures was 0.94 (95% confidence interval [CI] 0.89 to 0.97). Only TBF percentage (anthropometrics by the Durnin's table) appeared to be associated with time to reach target temperature: 0.93 (95% CI 0.87 to 0.99; P = 0.03).

Conclusion
The body composition measures from single-frequency impedance and anthropometrics appear to be very concordant. Only TBF percentage (anthropometrics) showed a significant but clinically irrelevant influence on time needed to achieve target temperature with hypothermia. We conclude that there are no indications to adjust current cooling practice toward the body composition of patients.
Glucocorticoid Regulation of the Promoter of 11β-Hydroxysteroid Dehydrogenase Type 1 Is Indirect and Requires CCAAT/Enhancer-Binding Protein-β
Authors: Sai Shuji , Esteves Cristina L. , Kelly Val , Michailidou Zoi , Anderson Karen , Coll Anthony P. , Nakagawa Yuichi , Ohzeki Takehiko , Seckl Jonathan R. , Chapman Karen E. 
Published: July 2008

Abstract11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inert 11keto-glucocorticoids to active 11β-hydroxy forms, thereby amplifying intracellular glucocorticoid action. Up-regulation of 11β-HSD1 in adipose tissue and liver is of pathogenic importance in metabolic syndrome. However, the mechanisms controlling 11β-HSD1 transcription are poorly understood. Glucocorticoids themselves potently increase 11β-HSD1 expression in many cells, providing a potential feed-forward system to pathology. We have investigated the molecular mechanisms by which glucocorticoids regulate transcription of 11β-HSD1, exploiting an A549 cell model system in which endogenous 11β-HSD1 is expressed and is induced by dexamethasone. We show that glucocorticoid induction of 11β-HSD1 is indirect and requires new protein synthesis. A glucocorticoid-responsive region maps to between −196 and −88 with respect to the transcription start site. This region contains two binding sites for CCAAT/enhancer-binding protein (C/EBP) that together are essential for the glucocorticoid response and that bind predominantly C/EBPβ, with C/EBPδ present in a minority of the complexes. Both C/EBPβ and C/EBPδ are rapidly induced by glucocorticoids in A549 cells, but small interfering RNA-mediated knockdown shows that only C/EBPβ reduction attenuates the glucocorticoid induction of 11β-HSD1. Chromatin immunoprecipitation studies demonstrated increased binding of C/EBPβ to the 11β-HSD1 promoter in A549 cells after glucocorticoid treatment. A similar mechanism may apply in adipose tissue in vivo where increased C/EBPβ mRNA levels after glucocorticoid treatment were associated with increased 11β-HSD1 expression. C/EBPβ is a key mediator of metabolic and inflammatory signaling. Positive regulation of 11β-HSD1 by C/EBPβ may link amplification of glucocorticoid action with metabolic and inflammatory pathways and may represent an endogenous innate host-defense mechanism.
Discovery and Application of Asymmetric Reaction by Multi-Functional Thioureas
Authors: Miyabe Hideto , Takemoto Yoshiji 
Published: July 2008

Abstract
Novel bifunctional organocatalysts, which possess a thiourea moiety and an amino group, were designed and synthesized. We discovered that bifunctional thiourea bearing a tertiary amino group significantly accelerated several nucleophilic addition reactions of active methylene compounds to electron-deficient double bonds. In these reactions, the double hydrogen-bonding activation of electrophiles bearing nitro, imide, and carbamate groups by the thiourea moiety and simultaneous deprotonation of nucleophiles by the dimethylamino group of bifunctional thiourea proved to play a crucial role for enhancing both reaction rate and enantioselectivity. We have demonstrated the utility of PEG-bound thiourea as a homogeneous catalyst. Although the reaction rate was somewhat decreased with PEG-bound thiourea, immobilization to a PEG support proved to facilitate the recovery and reuse of thiourea catalyst without affecting the chemical yield and enantioselectivity. A newly designed thiourea catalyst provided sufficient activation of organoboronic acids to facilitate the enantioselective Petasis transformation of quinolines even at low temperatures. A high degree of stereocontrol was achieved in the reaction of various quinolines and organoboronic acids by using a combination of H2O and NaHCO3 as additives.
Infrared-Induced Reaction on MoO3 Using a Tunable Infrared Free Electron Laser
Authors: Moula Md Golam , Sato Shinsuke , Irokawa Katsumi , Niimi Hironobu , Suzuki Shushi , Asakura Kiyotaka , Kuroda Haruo 
Published: July 2008

Abstract
We observed the IR-induced reaction of C2H5OH on MoO3 using a pulsed and tunable infrared free electron laser (IR-FEL). The IR-FEL-induced reaction showed wavelength dependency and requires light stronger than a certain threshold level. The C2H5OH was converted mainly to C2H4 only when the MoO3 was irradiated with focused IR-FEL at 967 and 814 cm−1 corresponding to Mo=O stretching modes, whereas IR light at 1200 cm−1 induced no reaction. The origin of this IR-FEL-induced reaction is discussed.
Electron Spin–Lattice Relaxation Times of Spin Probes in Aqueous Dispersions of a Unique Amphiphilic Compound Obtained by a Saturation Recovery Method
Authors: Nakagawa Kouichi 
Published: July 2008

Abstract
Electron spin–lattice relaxation times (T1e) of a unique nonionic amphiphilic compound, (poly(oxyethylene) hydrogenated castor oil, HCO) in aqueous dispersions, were investigated by electron paramagnetic resonance (EPR) and saturation recovery (SR) spectroscopies. The spin probes, 5-doxylstearic acid (5-DSA) and 3β-doxyl-5α-cholestane (CHL), were used to obtain T1e values for the head group region in the HCO membrane. Analysis of SR signals from both probes showed that the T1e value (≈5 μs at 20 °C) indicates relatively faster relaxation behavior in the region than that of 12-DSA. No abrupt change (such as phase transition) of the relaxation time was observed in the temperature region studied. Thus, the present T1e results indicate relative flexibility for both probe moieties in the membrane throughout the temperatures studied.
Curium(III) Complexation with Desferrioxamine B (DFO) Investigated Using Fluorescence Spectroscopy
Authors: Moll Henry , Glorius Maja , Bernhard Gert 
Published: July 2008

Abstract
Hydroxamate-type siderophores like desferrioxamine B (DFO) are the most common siderophores ubiquitously found in the environment. These naturally occurring chelating substances have the potential to enhance the solubility and mobility of actinides by forming soluble complexes. The unknown interaction between curium(III) and aqueous DFO species is the subject of this paper. The reactions between soluble species of curium(III) and DFO were studied at trace curium(III) concentrations (3×10−7 M) in 0.1 M NaClO4 using time-resolved laser-induced fluorescence spectroscopy (TRLFS). Three Cm3+–DFO species, MpHqLr, could be identified from the luminescence spectra, CmH2DFO2+, CmHDFO+, and CmDFO, having emission maxima at 599, 611, and 614 nm, respectively. The large formation constants, logβ121=31.62±0.23, logβ111=25.70±0.17, and logβ101=16.80±0.40, compared to those of other chelating agents illustrate the unique complexation properties of hydroxamate-type siderophores. An indirect excitation mechanism for the curium(III) luminescence was observed in the presence of the DFO molecules.
Synthesis and Absolute Structure of (−)-Umtatin
Authors: Yamaguchi Seiji , Kobayashi Masahide , Harada Shin-ichiro , Miyazawa Masahiro , Hirai Yoshiro 
Published: July 2008

Abstract
A new preparation of 2-(hydroxymethyl)chromones was developed via the new regio-selective six-membered cyclization of 1-[o-(tert-butyldimethylsiloxy)phenyl]but-2-yn-1-ones by a three-step treatment with 1) diethylamine (activation of the γ-position), 2) KF-18-crown-6 (deprotection), and 3) silica-gel (cyclization). A naturally occurring chiral hydroxymethylfurochromone, (−)-umtatin, was synthesized starting from chiral (R)-(−)-2-isopropenyl-4,6-dimethoxy-2,3-dihydrobenzofuran, and the absolute structure was determined to R.