bluuebunny/crossref_metadata_2025_split huggingface dataset:
Muscle Cross-Sectional Area and Structural Bone Strength Share Genetic and Environmental Effects in Older Women
Authors: Mikkola Tuija M , Sipilä Sarianna , Rantanen Taina , Sievänen Harri , Suominen Harri , Tiainen Kristina , Kaprio Jaakko , Koskenvuo Markku , Kauppinen Markku , Heinonen Ari 
Published: October 2008

Abstract
The purpose of this study was to estimate to what extent muscle cross-sectional area of the lower leg (mCSA) and tibial structural strength are influenced by common and trait-specific genetic and environmental factors. pQCT scans were obtained from both members of 102 monozygotic (MZ) and 113 dizygotic (DZ) 63- to 76-yr-old female twin pairs to estimate the mCSA of the lower leg, structural bending strength of the tibial shaft (BSIbend), and compressive strength of the distal tibia (BSIcomp). Quantitative genetic models were used to decompose the phenotypic variances into common and trait-specific additive genetic (A), shared environmental (C), and individual environmental (E) effects. The age-adjusted trivariate independent pathway model showed that the total relative contributions of A, C, and E were, respectively, 75%, 0%, and 25% for mCSA, 55%, 20%, and 25% for BSIbend, and 40%, 37%, and 23% for BSIcomp. In addition, the model showed that all three traits shared genetic and individual environmental factors. BSIbend and BSIcomp had common shared environmental factors and were also influenced by trait-specific genetic factors. In conclusion, the association between muscle cross-sectional area and structural bone strength has its origins in both genetic and environmental effects in older women. These results suggest that in older women the same genetic and environmental factors may predispose to or, conversely, protect from both sarcopenia and bone fragility.
Ethanol Impairs Estrogen Receptor Signaling Resulting in Accelerated Activation of Senescence Pathways, Whereas Estradiol Attenuates the Effects of Ethanol in Osteoblasts
Authors: Chen Jin-Ran , Lazarenko Oxana P , Haley Rani Lynn , Blackburn Michael L , Badger Thomas M , Ronis Martin J 
Published: October 2008

AbstractEpidemiological and animal studies have suggested that chronic alcohol consumption is a major risk factor for osteoporosis. Using bone from cycling female rats infused chronically with ethanol (EtOH) in vivo and osteoblastic cells in vitro, we found that EtOH significantly increased estrogen receptor α (ERα) and β (ERβ) mRNA and ERα protein levels. Treatment with 17β-estradiol (E2) in vivo and in vitro interfered with these effects of EtOH on bone and osteoblastic cells. ERα agonist propylpyrazoletriol (PPT) and ERβ agonist diarylpropionitrile (DPN) attenuated EtOH-induced ERα and ERβ gene overexpression, respectively. Similar to the ER antagonist ICI 182780, EtOH blocked nuclear translocation of ERα-ECFP in the presence of E2 in UMR-106 osteoblastic cells. EtOH also downregulated ERE-luc reporter activity. On the other hand, EtOH by itself upregulated some common ERα- and ERβ-mediated genes apparently by an ER-independent pathway. EtOH also transactivated the luciferase activity of the p21 promoter region independent of additional exogenous ERα, activated p21 and p53, and stimulated senescence-associated β-galactosidase activity in rat stromal osteoblasts. E2 treatment attenuated these EtOH actions. We conclude that inhibitory cross-talk between EtOH and E2 in osteoblasts on ERs, p53/p21, and cell senescence provides a pathophysiologic mechanism underlying bone loss and the protective effects of estrogens in alcohol-exposed females.
Simplified System for Absolute Fracture Risk Assessment: Clinical Validation in Canadian Women
Authors: Leslie William D , Tsang James F , Lix Lisa M 
Published: October 2008

Abstract
Absolute 10-yr fracture risk based on multiple factors is the preferred method for risk assessment. A simplified risk assessment system from sex, age, DXA, and two clinical risk factors (CRFs)—prior fracture and systemic corticosteroid (CS) use-has been used in Canada since 2005. This study was undertaken to evaluate this system in the Canadian female population. A total of 16,205 women ≥50 yr of age at the time of baseline BMD (1998–2002) were identified in a database containing all clinical DXA test results for the Province of Manitoba, Canada. Basal 10-yr fracture risk from age and minimum T-score (lumbar spine, femur neck, trochanter, total hip) was categorized as low (&lt;10%), moderate (10–20%), or high (&gt;20%). Health service records since 1987 were assessed for prior fracture codes (N = 5224), recent major CS use (N = 616), and fracture codes after BMD testing (mean, 3.1 yr of follow-up) for the hip, vertebrae, forearm, or humerus (designated osteoporotic, N = 757). Fracture risk predicted from age and minimum T-score alone showed a significant gradient in observed fracture rates (low 5.1 [95% CI, 4.1–6.4], moderate 11.5 [95% CI, 10.1–13.0], high 25.4 [95% CI, 23.2–27.9] per 1000 person-years; p-for-trend &lt;0.0001). There was an incremental increase in incident fracture rates from a prior fracture (13.9 [95% CI, 11.3–16.4] per 1000 person-years) or major CS use (11.2 [95% CI, 4.1–18.2] per 1000 person-years). This simplified fracture risk assessment system provides an assessment of fracture risk that is consistent with observed fracture rates.
Carboxypeptidase Z (CPZ) Links Thyroid Hormone and Wnt Signaling Pathways in Growth Plate Chondrocytes
Authors: Wang Lai , Shao Yvonne Y , Ballock R Tracy 
Published: October 2008

Abstract
Carboxypeptidase Z (CPZ) removes carboxyl-terminal basic amino acid residues, particularly arginine residues, from proteins. CPZ contains a cysteine-rich domain (CRD) similar to the CRD found in the frizzled family of Wnt receptors. We have previously shown that thyroid hormone regulates terminal differentiation of growth plate chondrocytes through activation of Wnt-4 expression and Wnt/β-catenin signaling. The Wnt-4 protein contains a C-terminal arginine residue and binds to CPZ through the CRD. The objective of this study was to determine whether CPZ modulates Wnt/β-catenin signaling and terminal differentiation of growth plate chondrocytes. Our results show that CPZ and Wnt-4 mRNA are co-expressed throughout growth plate cartilage. In primary pellet cultures of rat growth plate chondrocytes, thyroid hormone increases both Wnt-4 and CPZ expression, as well as CPZ enzymatic activity. Knockdown of either Wnt-4 or CPZ mRNA levels using an RNA interference technique or blocking CPZ enzymatic activity with the carboxypeptidase inhibitor GEMSA reduces the thyroid hormone effect on both alkaline phosphatase activity and Col10a1 mRNA expression. Adenoviral overexpression of CPZ activates Wnt/β-catenin signaling and promotes the terminal differentiation of growth plate cells. Overexpression of CPZ in growth plate chondrocytes also removes the C-terminal arginine residue from a synthetic peptide consisting of the carboxyl-terminal 16 amino acids of the Wnt-4 protein. Removal of the C-terminal arginine residue of Wnt-4 by site-directed mutagenesis enhances the positive effect of Wnt-4 on terminal differentiation. These data indicate that thyroid hormone may regulate terminal differentiation of growth plate chondrocytes in part by modulating Wnt signaling pathways through the induction of CPZ and subsequent CPZ-enhanced activation of Wnt-4.
Atorvastatin May Have No Effect on Acute Phase Reaction in Children After Intravenous Bisphosphonate Infusion
Authors: Srivastava Tarak , Haney Connie J , Alon Uri S 
Published: October 2008

Abstract
Intravenous bisphosphonate therapy is associated with acute phase reaction characterized by fever and musculoskeletal pain. Bisphosphonates have been shown in vitro to activate γδT-cells to proliferate and produce cytokines, suggesting a role in acute phase reaction, which can be effectively blocked by statins. We conducted a double-blind randomized crossover placebo controlled study in 12 children (12.1 ± 4.2 yr; 10 girls and 2 boys) receiving intravenous bisphosphonates to evaluate whether statins can be used to prevent acute phase reaction associated with therapy. Children received two cycles given 3–4 mo apart of intravenous bisphosphonate given on 2 consecutive days in each cycle. Atorvastatin 10 mg or placebo was given orally once a day for 3 days, starting the day before intravenous bisphosphonate therapy and on the 2 infusion days. We measured pain using a visual analog pain scale at five time points in 0–48 h, oxycodone use for pain, acetaminophen for fever, C-reactive protein (CRP), and total and percent γδT-cells. There was a nonsignificant decrease in pain, oxycodone use, and acetaminophen use with Atorvastatin compared with placebo. There was no difference in CRP and total or percent γδT-cells between the two groups. The results remained unchanged after adjustment for Atorvastatin versus placebo given with the first cycle. We conclude that in vivo Atorvastatin may not be as effective in modulating the acute phase reaction associated with intravenous bisphosphonate as would have been anticipated from in vitro studies.
Quantification of Methylmalonic Acid in Human Plasma with Hydrophilic Interaction Liquid Chromatography Separation and Mass Spectrometric Detection
Authors: Lakso Hans-Åke , Appelblad Patrik , Schneede Jörn 
Published: October 2008

Abstract
Background: Measurement of methylmalonic acid (MMA) in serum or plasma is useful for diagnosing cobalamin deficiency. We developed a method for quantifying MMA in plasma based on hydrophilic interaction liquid chromatography (HILIC) and single-stage negative electrospray ionization (ESI) mass spectrometry.
Methods: We deproteinized plasma samples (200 μL) with 800 μL acidified acetonitrile containing 0.17 μmol/L deuterated MMA (D3-MMA) internal standard, centrifuged the samples, and injected 4 μL of the supernatant into the LC-MS instrument. Separation was achieved within 3 min on a Merck SeQuant ZIC®-HILIC column with a mobile phase consisting of 4 volumes acetonitrile plus 1 volume 100 mmol/L ammonium acetate buffer, pH 4.5, at a flow rate of 400 μL/min. Subsequent column washing and reconditioning contributed to a total run time of 10 min. MMA and D3-MMA were quantified by single-ion monitoring (m/z 117.2 and 120.2, respectively) in negative ESI mode at a drying-gas flow rate of 10 L/min, 300 °C, and a capillary voltage of 3.0 kV.
Results: The estimated limits of MMA quantification and detection were 0.09 μmol/L and 0.03 μmol/L, respectively, in plasma. The assay was linear to 200 μmol/L. Interassay and intraassay CVs were ≤5% at all tested concentrations. Recoveries were 90%–93%.
Conclusions: This robust assay allows analysis of MMA in human plasma without derivatization. Sample preparation is simple and suitable for automation.
Simultaneous Measurement of Plasma Concentrations of Proinsulin and C-Peptide and Their Ratio with a Trefoil-Type Time-Resolved Fluorescence Immunoassay
Authors: De Pauw Pieter E M , Vermeulen Ilse , Ubani Ogonnaya C , Truyen Inge , Vekens Evilien M F , van Genderen Farah T , De Grijse Joeri W , Pipeleers Daniel G , Van Schravendijk Chris , Gorus Frans K 
Published: October 2008

AbstractBackground: When the concentrations of 2 or more substances are measured separately, their molar ratios are subject to the additive imprecisions of the different assays. We hypothesized that the cumulative error for concentration ratios of peptides containing a common sequence might be minimized by measuring the peptides simultaneously with a “trefoil-type” immunoassay.Methods: As a model of this approach, we developed a dual-label time-resolved fluorescence immunoassay (TRFIA) to simultaneously measure proinsulin, C-peptide, and the proinsulin–C-peptide ratio (PI/C). A monoclonal antibody captures all C-peptide–containing molecules, and 2 differently labeled antibodies distinguish between proinsulin-like molecules and true C-peptide.Results: The trefoil-type TRFIA was capable of measuring plasma C-peptide and proinsulin simultaneously without mutual interference at limits of quantification of 48 and 8125 pmol/L, and 2.1 and 197 pmol/L, respectively. Within-laboratory imprecision values for the trefoil-type TRFIA ranged between 8.4% and 12% for the hormone concentrations. Unlike the hormone results obtained with separate assays, imprecision did not increase when PI/C was calculated from trefoil assay results (P &lt; 0.05). Peptide concentrations were highly correlated with results obtained in individual comparison assays (r2 ≥ 0.965; P &lt; 0.0001). The total error for PI/C obtained with the trefoil-type TRFIA remained ≤25% over a broader C-peptide range than with separate hormone assays (79–7200 pmol/L vs 590–4300 pmol/L C-peptide). Preliminary data indicate little or no interference by heterophile antibodies.Conclusions: The developed trefoil-type TRFIA is a reliable method for simultaneous measurement of proinsulin, C-peptide, and PI/C and provides proof of principle for the development of other trefoil-type multiple-label immunoassays.
N-terminal polyglutamine-containing fragments inhibit androgen receptor transactivation function
Authors: Schiffer Niclas W. , Céraline Jocelyn , Hartl F. Ulrich , Broadley Sarah A. 
Published: October 2008

Abstract
Several neurodegenerative diseases, including Kennedy's disease (KD), are associated with misfolding and aggregation of polyglutamine (polyQ)-expansion proteins. KD is caused by a polyQ-expansion in the androgen receptor (AR), a key player in male sexual differentiation. Interestingly, KD patients often show signs of mild-to-moderate androgen insensitivity syndrome (AIS) resulting from AR dysfunction. Here, we used the yeast Saccharomyces cerevisiae to investigate the molecular mechanism behind AIS in KD. Upon expression in yeast, polyQ-expanded N-terminal fragments of AR lacking the hormone binding domain caused a polyQ length-dependent growth defect. Interestingly, while AR fragments with 67 Q formed large, SDS-resistant inclusions, the most pronounced toxicity was observed upon expression of 102 Q fragments which accumulated exclusively as soluble oligomers in the 100–600 kDa range. Analysis using a hormone-dependent luciferase reporter revealed that full-length polyQ-expanded AR is fully functional in transactivation, but becomes inactivated in the presence of the corresponding polyQ-expanded N-terminal fragment. Furthermore, the greatest impairment of AR activity was observed upon interaction of full-length AR with soluble AR fragments. Taken together, our results suggest that soluble polyQ-containing fragments bind to full-length AR and inactivate it, thus providing insight into the mechanism behind AIS in KD and possibly other polyglutamine diseases, such as Huntington's disease.
Role of tissue kallikrein-related peptidases in cervical mucus remodeling and host defense
Authors: Shaw Julie L.V. , Petraki Constantina , Watson Carole , Bocking Alan , Diamandis Eleftherios P. 
Published: October 2008

AbstractHuman tissue kallikrein-related peptidases (KLKs) are 15 hormonally regulated genes on chromosome 19q13.4 encoding secreted serine proteases. Many KLKs are expressed throughout the female reproductive system and found in cervico-vaginal fluid (CVF). Immunohistochemistry was performed to determine KLK localization in the female reproductive system (fallopian tube, endometrium, cervix and vagina tissues). KLK levels were measured in CVF and saliva over the menstrual cycle to study whether KLKs are regulated by hormonal changes during the cycle.In vitrocleavage analysis was performed to establish whether KLKs may play a role in vaginal epithelial desquamation, mucus remodeling or processing of antimicrobial proteins. KLKs were localized in the glandular epithelium of the fallopian tubes and endometrium, the cervical mucus-secreting epithelium and vaginal stratified squamous epithelium. KLK levels peaked in CVF and saliva after ovulation.In vitrocleavage analysis confirmed KLKs 5 and 12 as capable of digesting desmoglein and desmocollin adhesion proteins and cervical mucin proteins 4 and 5B. KLK5 can digest defensin-1α, suggesting it may aid in cervico-vaginal host defense. We provide evidence of potential physiological roles for KLKs in cervico-vaginal physiology: in desquamation of vaginal epithelial cells, remodeling of cervical mucus and processing of antimicrobial proteins.
Reduction of myocardial infarction by postischemic administration of the calpain inhibitor A-705253 in comparison to the Na+/H+exchange inhibitor Cariporide®in isolated perfused rabbit hearts
Authors: Neuhof Christiane , Fabiunke Verena , Speth Maria , Möller Achim , Fritz Hans , Tillmanns Harald , Neuhof Heinz , Erdogan Ali 
Published: October 2008

AbstractThe calpain inhibitor A-705253 and the Na+/H+-exchange inhibitor Cariporide®were studied in isolated perfused rabbit hearts subjected to 60 min occlusion of the ramus interventricularis of the left coronary artery (below the origin of the first diagonal branch), followed by 120 min of reperfusion. The inhibitors were added to the perfusion fluid solely or in combination at the beginning of reperfusion. Hemodynamic monitoring and biochemical analysis of perfusion fluid from the coronary outflow were performed. Myocardial infarct size and area at risk (transiently not perfused myocardium) were determined from left ventricular slices after a special staining procedure with Evans blue and 2,3,5-triphenyltetrazolium chloride. The infarcted area (dead myocardium) was 72.7±4.0% of the area at risk in untreated controls, but was significantly smaller in the presence of the inhibitors. The largest effect was observed with 10-6 M A-705253, which reduced the infarcted area to 49.2±4.1% of the area at risk, corresponding to a reduction of 33.6%. Cariporide®at 10-6 M reduced the infarct size to the same extent. The combination of both inhibitors, however, did not further improve cardioprotection. No significant difference was observed between the experimental groups in coronary perfusion, left ventricular pressure, heart rate, or in the release of lactate dehydrogenase and creatine kinase from heart muscle.
Rethinking low genus hyperelliptic Jacobian arithmetic over binary fields: interplay of field arithmetic and explicit formulæ
Authors: Avanzi R. , Thériault N. , Wang Z. 
Published: October 2008

Abstract
In this paper, we present several improvements on the best known explicit formulæ for hyperelliptic curves of genus three and four in characteristic two, including the issue of reducing memory requirements.
To show the effectiveness of these improvements and to allow a fair comparison of the curves of different genera, we implement all formulæ using a highly optimized software library for arithmetic in binary fields. This library was designed to minimize the impact of a whole series of overheads which have a larger significance as the genus of the curves increases. The current state of the art in attacks against the discrete logarithm problem is taken into account for the choice of the field and group sizes. Performance tests are done on two personal computers with very different architectures.
Our results can be shortly summarized as follows: Curves of genus three provide performance similar, or better, to that of curves of genus two, and these two types of curves can perform faster than elliptic curves – indeed on some processors often twice as fast. Curves of genus four attain a performance level comparable to elliptic curves. A large choice of curves is therefore available for the deployment of curve-based cryptography, with curves of genus three and four providing their own advantages as larger cofactors can be allowed for the group order.
Reaction of rhenium and carbon at high pressures and temperatures
Authors: Juarez-Arellano Erick A. , Winkler Björn , Friedrich Alexandra , Wilson Dan J. , Koch-Müller Monika , Knorr Karsten , Vogel Sven C. , Wall James J. , Reiche Helmut , Crichton Wilson , Ortega-Aviles Mayahuel , Avalos-Borja Miguel 
Published: October 2008

Abstract
A study of the reaction of rhenium with carbon at high-(P, T) conditions up to P
max = 67 GPa and T
max = 3800 K is presented. A hexagonal ReC
x
was identified as the stable phase at high-(P, T) conditions. A composition of ReC0.5 is proposed. No evidence for a cubic ReC polymorph with rocksalt structure, as suggested in the literature, or for any other phase was found at the P-T conditions explored. A preliminary P-T rhenium-carbon phase diagram has been derived and properties such as bulk moduli and elastic stiffness coefficients were obtained.
Electron density of a new EGFR Tyrokinase-inhibitor at 100 K, consideration of different models
Authors: Mebs Stefan , Lüth Anja , Löwe Wolfgang , Paulmann Carsten , Luger Peter 
Published: October 2008

Abstract
The electron density (ED) of a substituted 4-(indol-3-yl)-quinazoline, a newly developed anti-cancer drug, was determined from a high resolution X-ray data set measured at 100 K using synchrotron radiation. Because the structure contains a chlorine atom, which has a diffuse outer electron shell and is therefore beyond standard modeling, the influence of the model on the bond topological and atomic properties was studied following Bader's approach of ‘Atoms In Molecules’ (AIM). The expansion/contraction parameters κ and κ′ of the four atoms being constitutive for the Cl—C-bond and the F—C-bond were obtained by calculation of theoretical structure factors of a model compound and assigned in subsequent multipole refinements. The κ and κ′-values for all other non H-atoms atoms were taken from the literature. The effect of two different sets of κ and κ′ (1.20/1.20 and 1.13/1.29) for the hydrogen atoms was evaluated for the topological properties at bonds to hydrogen atoms (including hydrogen bonds) and to the atomic properties of the hydrogen atoms. Furthermore the effect of particular n

l
-sets for the chlorine atom to bond topological descriptors of the Cl—C-bond was investigated for the theoretical structure factors and compared with experiment. All results were compared with corresponding theoretical findings from a single point calculation at experimental geometry.
Solid state molecular assemblies of five bile acid derivatives
Authors: Bertolasi Valerio , Ferretti Valeria , Fantin Giancarlo , Fogagnolo Marco 
Published: October 2008

Abstract
The crystal structures of five bile acid derivatives are reported: 1: 6α,7α-Dihydroxy-5β-cholan-24-oic acid; 2: 3α,6α-Dihydroxy-5β-cholan-24-oic acid (Hyodeoxycholic acid); 3: 3α,7α,12α-Trihydroxy-5β-cholan-24-hydrazide hemihydrate; 4: 3-Dimethyl ketal,7,12-dioxo-5β-cholan-24-oic acid and 5: 3α,7α-Di-O-acetyl-12-oxo-5β-cholan-24-oic acid methyl ester. In all the structures the four saturated cycles, forming the common alicyclic steroidal skeleton, have the same conformation, while the flexible side chain adopts different conformations. Whereas all the crystal structures of Cholic Acid inclusion compounds are characterized by the formation of a bilayer-type structure with channels within the lipophilic layers, the chemical variations of the substituents on the cholanic framework induce remarkable changes in the H-bond scheme and in the crystal packing arrangements. For instance, the structures 1, 2, having a different number and position of the hydroxyl groups on the rigid skeleton, display a variety of supramolecular architectures dominated by networks of cooperative …O—H…O… H-bonds which do not produce typical molecular layers and channels of Cholic Acid inclusion compounds. Cholic hydrazide hemihydrate, 3, where both the hydrazide group and water molecule are strongly involved in the H-bond system, forms an overall structural motif similar to that observed in CA inclusion compounds containing hydrophilic and lipophilic layers and small channels. Compound 4, containing only the carboxylic OH group as H-bond donor, makes simple antiparallel chains of molecules, while compound 5, lacking of H-bond donors, forms a crystal aggregation dominated by weak C—H…O contacts and van der Waals interactions leading to a crystal packing where neither molecular layers nor channels are recognizable.