bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic Regions Identified for BMD in a Large Sample Including Epistatic Interactions and Gender-Specific Effects
Authors: Xiao Peng , Shen Hui , Guo Yan-Fang , Xiong Dong-Hai , Liu Yao-Zhong , Liu Yong-Jun , Zhao Lan-Juan , Long Ji-Rong , Guo Yan , Recker Robert R , Deng Hong-Wen 
Published: September 2006

Abstract
A genome-wide linkage scan was conducted using a large white sample to identify QTLs for BMD. We found QTLs in the total sample and the gender-specific subgroups, as well as significant epistatic interactions underlying BMD variations.
Introduction: Low BMD is an important risk factor for osteoporosis and under strong genetic control.
Materials and Methods: To identify quantitative trait loci (QTLs) for regulation of BMD, we performed a large-scale whole genome linkage scan (WGS) involving 4126 individuals from 451 families. In addition to the conventional linkage analyses in the total combined sample of males and females, we conducted epistatic interaction analyses and gender-specific linkage analyses.
Results: Significant linkage was detected on 5q23 for wrist BMD (LOD = 3.39) and 15q13 for female spine BMD (LOD = 4.49). For spine BMD, we revealed significant epistatic interactions between 3p25 and 2q32 (p = 0.0022) and between 3p25 and 11q23 (p = 0.0007). We replicated several genomic regions that showed linkage with BMD in previous studies by others and ours, such as 3p21, 1p36, and Xq27.
Conclusions: This study highlights the importance of large sample size, incorporation of epistatic interaction, and consideration of gender-specific effects in identifying QTLs for BMD variation. The results of this study provide a foundation for the future fine mapping and gene identification in our population.
α9β1: A Novel Osteoclast Integrin That Regulates Osteoclast Formation and Function
Authors: Rao Hongwei , Lu Ganwei , Kajiya Hiroshi , Garcia-Palacios Veronica , Kurihara Noriyoshi , Anderson Judy , Patrene Ken , Sheppard Dean , Blair Harry C , Windle Jolene J , Choi Sun Jin , Roodman G David 
Published: September 2006

Abstract
We identified a previously unknown integrin, α9β1, on OCLs and their precursors. Antibody to α9 inhibited OCL formation in human marrow cultures, and OCLs from α9 knockout mice had a defect in actin ring reorganization and an impaired bone resorption capacity.
Introduction: Integrins play important roles in osteoclast (OCL) formation and function. Mature OCLs mainly express αvβ3 integrin, a heterodimer adhesion receptor that has been implicated in osteoclastic bone resorption. We identified ADAM8, a disintegrin and metalloproteinase, as a novel stimulator of OCL differentiation and showed that the disintegrin domain of ADAM8 mediated its effects on OCL formation. Because the disintegrin domain of ADAM8 does not bind Arg-Gly-Asp (RGD) sequences, we determined which integrin bound ADAM8 and characterized its role in OCL formation and activity.
Materials and Methods: Chinese hamster ovary cells (CHO) expressing different integrin subunits were tested for their capacity to bind the disintegrin domain of ADAM8. Mouse or human bone marrow cells and purified OCL precursors were tested for α9β1 integrin expression by Western blot, immunocytochemistry, and real-time RT-PCR. A monoclonal antibody to human α9 was used to block α9β1 on OCL precursors stimulated by 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] or RANKL. Vertebrae of 7-day-old α9−/− mice and wildtype (WT) littermates were compared using bone histomorphometry and 3D μCT analysis.
Results: α9 integrin was expressed by mouse and human bone marrow–derived OCLs and their precursors. Importantly, the anti-α9 antibody inhibited human OCL formation stimulated by 1α,25(OH)2D3 or RANKL dose-dependently. Furthermore, analysis of OCLs formed in marrow cultures from α9−/− mice showed that the OCLs formed were more contracted and formed significantly less bone resorption pits on dentin slices. Histologic analysis of α9−/− vertebrae showed thickened trabecular regions and retained cartilage within vertebral bodies of α9−/− mice. 3D μCT analysis of α9−/− vertebrae also showed a significant increase in trabecular bone volume/total tissue volume and a tendency for decreased trabecular separation compared with WT mice.
Conclusions: These results support a previously unknown role for α9β1 integrin in OCL formation and function.
Reproducibility of Risk Figures in 2nd-Trimester Maternal Serum Screening for Down Syndrome: Comparison of 2 Laboratories
Authors: Benn Peter A , Makowski Gregory S , Egan James FX , Wright Dave 
Published: September 2006

Abstract
Background: Analytical error affects 2nd-trimester maternal serum screening for Down syndrome risk estimation. We analyzed the between-laboratory reproducibility of risk estimates from 2 laboratories.
Methods: Laboratory 1 used Bayer ACS180 immunoassays for α-fetoprotein (AFP) and human chorionic gonadotropin (hCG), Diagnostic Systems Laboratories (DSL) RIA for unconjugated estriol (uE3), and DSL enzyme immunoassay for inhibin-A (INH-A). Laboratory 2 used Beckman immunoassays for AFP, hCG, and uE3, and DSL enzyme immunoassay for INH-A. Analyte medians were separately established for each laboratory. We used the same computational algorithm for all risk calculations, and we used Monte Carlo methods for computer modeling.
Results: For 462 samples tested, risk figures from the 2 laboratories differed &gt;2-fold for 44.7%, &gt;5-fold for 7.1%, and &gt;10-fold for 1.7%. Between-laboratory differences in analytes were greatest for uE3 and INH-A. The screen-positive rates were 9.3% for laboratory 1 and 11.5% for laboratory 2, with a significant difference in the patients identified as screen-positive vs screen-negative (McNemar test, P &lt;0.001). Computer modeling confirmed the large between-laboratory risk differences.
Conclusion: Differences in performance of assays and laboratory procedures can have a large effect on patient-specific risks. Screening laboratories should minimize test imprecision and ensure that each assay performs in a manner similar to that assumed in the risk computational algorithm.
Measurement of Urinary Metanephrines to Screen for Pheochromocytoma in an Unselected Hospital Referral Population
Authors: Brain Keith L , Kay Jonathan , Shine Brian 
Published: September 2006

Abstract
Background: Despite the rarity of pheochromocytoma, diagnosis is important because of the dangers of uncontrolled severe hypertension and the availability of very effective surgical treatment. Urinary or plasma catecholamines or catecholamine derivatives are commonly used to screen for pheochromocytomas before imaging, but data from 24-h urinary metanephrine results, patient age, and sex may better predict tumors in populations with a low pretest probability.
Methods: We retrospectively studied outcomes of an unselected population (1819 patients) referred to a tertiary hospital laboratory for urinary metanephrine testing and investigated the usefulness of some simple derivative measures for detecting pheochromocytoma. We normalized values for urinary 24-h excretion of metanephrine, normetanephrine, and 3-methoxytyramine by dividing by an age- and sex-specific reference range. We then compared pheochromocytoma prediction by the use of products of these normalized measures with the gold standard of biopsy-confirmed tumor.
Results: The product of the excretion of normalized metanephrine (nMAD) and normalized normetanephrine (nNMT) (nMAD·nNMT) was a highly sensitive (100%) and specific (99.1%) measure, yielding a positive predictive value of 82%. ROC curves were not improved by including the normalized 3-methoxytyramine concentrations in the product. The test for nMAD·nNMT gave higher sensitivity and specificity than the tests for either substance alone.
Conclusion: The test for nMAD·nNMT is a useful measure for identifying pheochromocytoma in a population with a low pretest probability.
Rapid, Simple, and Sensitive Immunoagglutination Assay with SiO2 Particles and Quartz Crystal Microbalance for Quantifying Schistosoma japonicum Antibodies
Authors: Wang Hua , Zhang Yun , Yan Bani , Liu Li , Wang Shiping , Shen Guoli , Yu Ruqin 
Published: September 2006

AbstractBackground: The resurgence of the parasitic disease schistosomiasis calls for more efficient diagnostic tests. We developed a rapid, simple, portable, and sensitive immunoagglutination assay that uses SiO2 particles and quartz crystal microbalance (QCM) for quantifying Schistosoma japonicum (Sj) antibodies (SjAb).Methods: We prepared submicrometer-sized silica particles derivatized with Sj antigens as replacements for traditional latex microspheres to specifically agglutinate in the presence of SjAb targets, and we used the QCM monitor to measure the resulting frequency shifts. We optimized the assay medium by adding poly(ethylene glycol) (PEG) as a response accelerator of immunoagglutination. To minimize or eliminate any nonspecific agglutination or adsorption interferences, we conducted appropriate sealing procedures separately for silica particles and the QCM probe.Results: The measured frequency changes were linearly related to the SjAb concentrations in infected rabbit serum. The PEG-assisted immunoagglutination system was quantitatively sensitive to SjAb concentrations ranging from ∼0.70 to 32.31 mg/L, with a detection limit of ∼0.46 mg/L. The obtained linear regression equation was: y = 43.61 x + 80.44 (r = 0.9872). Several serum specimens were evaluated with the developed QCM immunoassay and the results were compared with ELISA, validating the feasibility of practical applications.Conclusions: This novel immunoagglutination-based QCM detection format is rapid, simple to use, and more portable than conventional diagnostic immunoassays, thus offering a promising alternative tool that can be used for point-of-care clinical diagnosis of schistosomiasis, particularly in epidemic situations.
Improvement of Technical and Analytical Performance in DNA Sequencing by External Quality Assessment-Based Molecular Training
Authors: Dorn-Beineke Alexandra , Ahmad-Nejad Parviz , Pfeiffer Ulrike , Ramsden Simon , Pazzagli Mario , Neumaier Michael 
Published: September 2006

AbstractBackground: From 2003 to 2005, the European Union supported the EQUAL-initiative to develop methodological external quality assessment (EQA) schemes for genotyping (EQUALqual), quantitative PCR (EQUALquant), and sequencing (EQUALseq). As a relevant part of the EQUALseq program, a training course was held subsequent to the first EQA Program (EQAP1). The success of this course was reassessed in a 2nd EQUALseq round (EQAP2).Methods: In September 2005, a 3-day training course took place. We invited 8 laboratories with below-average performance in EQAP1 to improve their methodological and analytical/proficiency skills by lectures and practical work. To compare the results of the pretraining and posttraining EQUALseq rounds, we distributed 2 samples used in the first EQUAL round, but this time we provided different oligonucleotide sets. We evaluated the results by means of a previously described scoring system.Results: In EQAP2, 6 laboratories returned complete data sets, corresponding to an overall 14% of the 43 laboratories that had finished EQAP1. The scoring results for samples A (P = 0.0025) and B (P = 0.0125) demonstrated a significant improvement in EQAP2. Overall, a substantial improvement of technical and interpretative skills was demonstrated (P = 0.0051). In general, the workshop experience was highly rated by the participants.Conclusions: Methodologic EQAPs in DNA sequencing are appropriate tools to uncover strengths and weaknesses in both technique and proficiency, emphasizing the need for mandatory EQAPs. Training courses, together with 2nd-round reiterations, should be implemented into methodological EQAPs in molecular diagnostics to improve technical performance and proficiency in genetic testing.
Circulating Proteasomes Are Functional and Have a Subtype Pattern Distinct from 20S Proteasomes in Major Blood Cells
Authors: Zoeger Annette , Blau Michael , Egerer Karl , Feist Eugen , Dahlmann Burkhardt 
Published: September 2006

Abstract
Background: 20S proteasomes, the proteolytic core particles of the major intracellular protein degradative pathway, are potential disease markers because they are detectable in human plasma as circulating proteasomes and their concentrations are increased in patients suffering from various diseases. To investigate the origin of circulating proteasomes, we compared some of their features with those of proteasomes isolated from major blood cells.
Methods: We isolated circulating proteasomes from the plasma of 2 patients with rheumatoid arthritis and 2 with systemic lupus erythematosus and from human plasma from healthy donors. We purified the proteasomes to apparent homogeneity and then used electron microscopy for imaging and chromatography for subtype spectrum analysis. We compared subtype results with those from 20S proteasomes purified from 4 major blood cell populations. We also tested proteasomes for enzymatic activity and immunosubunit content.
Results: Circulating proteasomes from plasma of healthy donors and from patients with autoimmune disease were found to have the same size and shape as erythrocyte proteasomes, be proteolytically active, and contain standard- and immunosubunits. Chromatography revealed 6 circulating proteasome subtype peaks in healthy donor plasma and 7 in patient donor plasma. Proteasomes from erythrocytes had 3 subtype peaks and those of monocytes, T-lymphocytes, and thrombocytes each had 5 different subtype peaks.
Conclusion: Circulating proteasomes were intact and enzymatically active in plasma from healthy donors and from patients with autoimmune disease. Because the subtype patterns of circulating proteasomes clearly differ from those of proteasomes from blood cells, these cells cannot be regarded as a major source of circulating proteasomes.
Lipoprotein(a) in the Cerebrospinal Fluid of Neurological Patients with Blood–Cerebrospinal Fluid Barrier Dysfunction
Authors: Pepe Gabriella , Chimienti Guglielmina , Liuzzi Grazia Maria , Lamanuzzi Biagia Leila , Nardulli Marina , Lolli Francesco , Anglés-Cano Eduardo , Matà Sabrina 
Published: September 2006

AbstractBackground: Lipoprotein(a) [Lp(a)] is a recognized pathogenic particle in human plasma, but its presence in the cerebrospinal fluid and its possible role in the central nervous system have not been documented. We tested the hypothesis that apolipoprotein(a) [apo(a)], free or as a component of the Lp(a) particle, can cross the blood–cerebrospinal fluid barrier and be found in the cerebrospinal fluid of patients affected by neurologic pathologies.Methods: We studied paired cerebrospinal fluid/serum samples from 77 patients with inflammatory (n = 20) or noninflammatory (n = 34) blood–cerebrospinal fluid barrier dysfunction and without blood–cerebrospinal fluid barrier dysfunction (n = 23). We used ELISA to measure Lp(a) concentrations and Western blot and immunodetection to analyze apo(a) isoforms in native and reducing conditions.Results: Entire Lp(a) with either small or large apo(a) isoforms was present in the cerebrospinal fluid of patients with blood–cerebrospinal fluid barrier dysfunction, regardless of its pathogenesis. Multiple linear regression analysis showed that both serum Lp(a) concentration (P = 0.003) and cerebrospinal fluid/serum albumin ratio (P &lt;0.001) were predictors of the Lp(a) concentration in cerebrospinal fluid.Conclusions: Our results demonstrate that Lp(a) can cross a dysfunctional blood–cerebrospinal fluid barrier. The unusual presence of Lp(a) in the cerebrospinal fluid could extend some of its known pathogenic effects to the central nervous system.
Inhibitory Effects of Micronized Fenofibrate on Carotid Atherosclerosis in Patients with Essential Hypertension
Authors: Zhu Shiming , Su Guohai , Meng Qing H 
Published: September 2006

Abstract
Background: The coexistence of hypertension and dyslipidemia synergistically increases the risk of cardiovascular events. We investigated the effect of the lipid-lowering agent micronized fenofibrate on inhibition of carotid atherosclerosis in patients with essential hypertension and mild hyperlipidemia.
Methods: We measured serum lipid profiles and inflammatory markers on chemistry or immune analyzers and common or internal carotid intima-media thickness (IMT) and diameter (D) by ultrasonography.
Results: Patients receiving micronized fenofibrate for 24 months in addition to antihypertensive treatment had decreased concentrations of total cholesterol, LDL-cholesterol, triglyceride, apolipoprotein B100, oxidized LDL, high-sensitivity C-reactive protein, P-selectin, and cytokines. These patients had increased concentrations of HDL-cholesterol, apolipoprotein A-I, and nitric oxide. Common carotid artery IMT (CCAIMT) and internal carotid artery IMT (ICAIMT) remained unchanged during the 24-month intervention. Moreover, the mean CCAIMT/D ratio and ICAIMT/D ratio were significantly decreased in the fenofibrate intervention group. In contrast, CCAIMT/D and ICAIMT/D ratios were increased in the control group. The incidence rates of carotid artery plaque formation and stroke in the fenofibrate intervention group were significantly lower than those in the control group.
Conclusion: The combination of antihypertensive agents with micronized fenofibrate can effectively prevent the progression of carotid atherosclerosis and reduce the incidence of stroke in patients with essential hypertension.
Dppa2 and Dppa4 Are Closely Linked SAP Motif Genes Restricted to Pluripotent Cells and the Germ Line
Authors: Maldonado-Saldivia Joanna , van den Bergen Jocelyn , Krouskos Margarita , Gilchrist Mike , Lee Caroline , Li Ruili , Sinclair Andrew H. , Surani M. Azim , Western Patrick S. 
Published: September 2006

Abstract
Despite the enormous medical potential of ESCs, the molecular mechanisms conferring the ability to differentiate into all cell types of the embryo remain elusive. We used an in silico approach to identify genes expressed exclusively in mouse preimplantation embryos and pluripotent cell lines. Two of these genes were developmental pluripotency-associated gene 2 (Dppa2) and Dppa4, which we show are closely linked genes encoding putative nuclear SAP domain proteins expressed in human and mouse pluripotent stem cells and germ cell tumor-derived embryonal carcinoma cells. In the mouse, these genes are transcribed in germinal vesicle-stage oocytes and throughout the cleavage stages of embryogenesis. They then become restricted to the pluripotent inner cell mass of blastocysts and are subsequently downregulated. After gastrulation, Dppa2 and Dppa4 are expressed only in the developing germ line, showing that these genes mark cells of the pluripotent cycle. In the germ line, both genes are downregulated as the germ cells commit to the oogenic pathway or soon after commitment to the spermatogenic pathway. We have observed similar germ line expression profiles for other pluripotent markers, and these results are consistent with the hypothesis that pluripotent markers must be downregulated during fetal germ line development, a process that may be required to facilitate appropriate germ line differentiation. The study of expression and function of pluripotent markers such as Dppa2 and Dppa4 is likely to unveil new aspects of the regulation of pluripotency and germ line development in mammals.
Multiscale modeling of transport and residence times in nanostructured membranes
Authors: Albo Simón E. , Broadbelt Linda J. , Snurr Randall Q. 
Published: September 2006

AbstractModeling and simulation at different scales were used to study mass transport and residence times of particles in nanostructured membranes with uniform cylindrical pores of 10–150 nm diameter and up to 5 μm long. Analytical equations of the possible mass‐transport mechanisms inside the pores were used to determine that diffusion dominates over convection under the conditions of interest for selective oxidation: 700 K and pressure near atmospheric. Molecular dynamics simulations showed that surface diffusion is present only at temperatures < 700 K. Knudsen diffusion was identified as the dominant mechanism. Simulations based on its principles were performed using an ensemble of particles in a boundary‐driven simulation cell, providing the average number of hits between a particle and the pore wall and the dependency of the residence time on the pore dimensions. The differences between operating a nanostructured membrane reactor in sweep‐gas and pass‐through modes were also investigated. © 2006 American Institute of Chemical Engineers AIChE J, 2006
Extending the Scope of NMR Spectroscopy with Microcoil Probes
Authors: Schroeder Frank C. , Gronquist Matthew 
Published: September 2006

AbstractCapillary NMR (CapNMR) spectroscopy has emerged as a major breakthrough for increasing the mass‐sensitivity of NMR spectroscopic analysis and enabling the combination of NMR spectroscopy with other analytical techniques. Not only is the acquisition of high‐sensitivity spectra getting easier but the quality of CapNMR spectra obtained in many small‐molecule applications exceeds what can be accomplished with conventional designs. This Minireview discusses current CapNMR technology and its applications for the characterization of mass‐limited, small‐molecule and protein samples, the rapid screening of small‐molecule or protein libraries, as well as hyphenated techniques that combine CapNMR with other analytical methods.
Luminescent lanthanide molecular‐based hybrid materials bridged through novel urethane linkages
Authors: Yan Bing , Zhou Bing , Wang Qian‐Ming 
Published: September 2006

AbstractNovel organosilicates with covalently linked functional modified aromatic acid have been synthesized from 3‐aminopropyl triethoxysilane (APS) grafted 4‐ethoxy benzoic acid (EB‐Si) and terbium ions via a simple low‐temperature route. The existence of covalent bonds between EB‐Si and silica matrices was shown by the hydrolysis and polycondensation processes of ethoxysilyl groups. Luminescence spectra were used to characterize the photophysical properties of the obtained hybrid material and the above spectroscopic data reveal that the triplet energy of modified para ethoxy benzoic acid in this favorable hybrid system matches the emissive energy level of RE3+. Copyright © 2006 John Wiley & Sons, Ltd.
Heck reactions of aryl halides with alk‐1‐en‐3‐ol derivatives catalysed by a tetraphosphine–palladium complex
Authors: Berthiol Florian , Doucet Henri , Santelli Maurice 
Published: September 2006

Abstractcis,cis,cis‐1,2,3,4‐Tetrakis(diphenylphosphinomethyl)cyclopentane–[PdCl(C3H5)]2 efficiently catalyses the Heck reaction of alk‐1‐en‐3‐ol with a variety of aryl halides. In the presence of hex‐1‐en‐3‐ol or oct‐1‐en‐3‐ol, the β‐arylated carbonyl compounds were selectively obtained. Turnover numbers up to 84 000 can be obtained for this reaction. Linalool and 2‐methylbut‐3‐en‐2‐ol led regio‐ and stereoselectively to the corresponding (E)‐1‐arylalk‐1‐en‐3‐ol derivatives. A minor electronic effect of the substituents of the aryl bromide was observed. Quite similar reaction rates were generally observed in the presence of activated aryl bromides such as bromoacetophenone and deactivated aryl bromides such as bromoanisole, indicating that, with these alkenols and this catalyst, the oxidative addition of aryl bromides to palladium is not the rate‐limiting step. It should be noted that this reaction also proceeds with sterically very congested aryl bromides such as 9‐bromoanthracene or 2,4,6‐triisopropylbromobenzene or with a vinyl bromide. On the other hand, low yields were obtained with aryl chlorides. Copyright © 2006 John Wiley & Sons, Ltd.
Novel photoswitching dithienylethenes with ferrocene units
Authors: Yin Jun , Yu Guang‐Ao , Tu Haiyang , Liu Sheng Hua 
Published: September 2006

AbstractTwo novel dithienylethenes with ferrocene units were synthesized by Wittig reaction. The structure of 2a has been established by X‐ray diffraction studies. They could reversibly interconvert between two thermally stable forms, an open and a closed one, using light of different wavelengths as triggers. Copyright © 2006 John Wiley & Sons, Ltd.