bluuebunny/crossref_metadata_2025_split huggingface dataset:
QTL Analysis of Trabecular Bone in BXD F2 and RI Mice
Authors: Bower Abbey L , Lang Dean H , Vogler George P , Vandenbergh David J , Blizard David A , Stout Joseph T , McClearn Gerald E , Sharkey Neil A 
Published: July 2006

Abstract
A sample of 693 mice was used to identify regions of the mouse genome associated with trabecular bone architecture as measured using μCT. QTLs for bone in the proximal tibial metaphysis were identified on several chromosomes indicating regions containing genes that regulate properties of trabecular bone.
Introduction: Age-related osteoporosis is a condition of major concern because of the morbidity and mortality associated with osteoporotic fractures in humans. Osteoporosis is characterized by reduced bone density, strength, and altered trabecular architecture, all of which are quantitative traits resulting from the actions of many genes working in concert with each other and the environment over the lifespan. μCT gives accurate measures of trabecular bone architecture providing phenotypic data related to bone volume and trabecular morphology. The primary objective of this research was to identify chromosomal regions called quantitative trait loci (QTLs) that contain genes influencing trabecular architecture as measured by μCT.
Materials and Methods: The study used crosses between C57BL/6J (B6) and DBA/2J (D2) as progenitor strains of a second filial (F2) generation (n = 141 males and 148 females) and 23 BXD recombinant inbred (RI) strains (n ≈︁ 9 of each sex per strain). The proximal tibial metaphyses of the 200-day-old mice were analyzed by μCT to assess phenotypic traits characterizing trabecular bone, including bone volume fraction, trabecular connectivity, and quantitative measures of trabecular orientation and anisotropy. Heritabilities were calculated and QTLs were identified using composite interval mapping.
Results: A number of phenotypes were found to be highly heritable. Heritability values for measured phenotypes using RI strains ranged from 0.15 for degree of anisotropy in females to 0.51 for connectivity density in females and total volume in males. Significant and confirmed QTLs, with LOD scores ⩾4.3 in the F2 cohort and ⩾1.5 in the corresponding RI cohort were found on chromosomes 1 (43 cM), 5 (44 cM), 6 (20 cM), and 8 (49 cM). Other QTLs with LOD scores ranging from 2.8 to 6.9 in the F2 analyses were found on chromosomes 1, 5, 6, 8, 9, and 12. QTLs were identified using data sets comprised of both male and female quantitative traits, suggesting similar genetic action in both sexes, whereas others seemed to be associated exclusively with one sex or the other, suggesting the possibility of sex-dependent effects.
Conclusions: Identification of the genes underlying these QTLs may lead to improvements in recognizing individuals most at risk for developing osteoporosis and in the design of new therapeutic interventions.
Cholesterol-Sensing Receptors, Liver × Receptor α and β, Have Novel and Distinct Roles in Osteoclast Differentiation and Activation
Authors: Robertson Kirsten M , Norgård Maria , Windahl Sara H , Hultenby Kjell , Ohlsson Claes , Andersson Göran , Gustafsson Jan-Åke 
Published: July 2006

Abstract
The liver × receptor (α,β) is responsible for regulating cholesterol homeostasis in cells. However, our studies using the LXRα−/−, LXRβ−/−, and LXRα−/−β−/− mice show that both LXRα and β are also important for bone turnover, mainly by regulating osteoclast differentiation/activity.
Introduction: The liver × receptors (α,β) are primarily responsible for regulating cholesterol homeostasis within cells and the whole body. However, as recent studies show that the role for this receptor is expanding, we studied whether the LXRs could be implicated in bone homeostasis and development.
Materials and Methods: pQCT was performed on both male and female LXRα−/−, LXRβ−/−, LXRα−/−β−/−, and WT mice at 4 months and 1 year of age. Four-month-old female mice were additionally analyzed with reference to qPCR, immunohistochemistry, histomorphometry, transmission electron microscopy, and serum bone turnover markers.
Results: At the mRNA level, LXRβ was more highly expressed than LXRα in both whole long bones and differentiating osteoblast-like MC3T3-E1 and osteoclast-like RAW 264.7 cells. Four-month-old female LXRα−/− mice had a significant increase in BMD because of an increase in all cortical parameters. No difference was seen regarding trabecular BMD. Quantitative histomorphometry showed that these mice had significantly more endosteal osteoclasts in the cortical bone; however, these cells appeared less active than normal cells as suggested by a significant reduction in serum levels of cross-linked carboxyterminal telopeptides of type I collagen (CTX) and a reduction in bone TRACP activity. Conversely, the female LXRβ−/− mice exhibited no change in BMD, presumably because a significant decline in the number of the trabecular osteoclasts was compensated for by an increase in the expression of the osteoclast markers cathepsin K and TRACP. These mice also had a significant decrease in serum CTX, suggesting decreased bone resorption; however, in addition presented with an increase in the expression of osteoblast associated genes, bone formation markers, and serum leptin levels.
Conclusions: Our findings show that both LXRs influence cellular function within the bone, with LXRα having an impact on osteoclast activity, primarily in cortical bone, whereas LXRβ modulates trabecular bone turnover.
Osteocytes Use Estrogen Receptor α to Respond to Strain but Their ERα Content Is Regulated by Estrogen
Authors: Zaman Gul , Jessop Helen L , Muzylak Mariusz , De Souza Roberto L , Pitsillides Andrew A , Price Joanna S , Lanyon Lance L 
Published: July 2006

Abstract
The role of mechanical strain and estrogen status in regulating ERα levels in bone cells was studied in female rats. OVX is associated with decreased ERα protein expression/osteocyte, whereas habitual strain and artificial loading has only a small but positive effect, except on the ulna's medial surface, where artificial loading stimulates reversal of resorption to formation.
Introduction: Osteoporosis is the most widespread failure of bones' ability to match their architectural strength to their habitual load bearing. In men and women, the severity of bone loss is associated with bioavailability of estrogen. This association could result from the estrogen receptor (ER) involvement in bone cells' adaptive response to loading.
Materials and Methods: In vivo semiquantitative analysis of the amount of ERα protein per osteocyte was performed in immuno-cytochemically stained sections from control and loaded rat ulna, as well as tibias of ovariectomy (OVX) and sham-operated female rats. In vitro, the effect of exogenous estrogen (10−8 M) and mechanical strain (3400 μϵ, 1 Hz, 600 cycles) on the expression of ERα mRNA levels was assessed in ROS 17/2.8 cells in monolayers using real-time PCR and ER promoter activity. ERα translocation in response to exogenous estrogen and mechanical strain was assessed in both ROS 17/2.8 and MLO-Y4 cells.
Results: More than 90 percent of tibial osteocytes express ERα, the level/osteocyte being higher in cortical than cancellous bone. OVX is associated with decreased ERα protein expression/osteocyte, whereas in the ulna habitual strain and that caused by artificial loading had only a small but positive effect, except on the medial surface, where loading stimulates reversal of resorption to formation. In unstimulated osteocytes and osteoblasts in situ, and osteocyte-like and osteoblast-like cells in vitro, ERα is predominantly cytoplasmic. In vitro, both strain and estrogen stimulate transient ERα translocation to the nucleus and transient changes in ERα mRNA. Strain but not estrogen also induces discrete membrane localization of ERα.
Conclusions: Bone cells' responses to both strain and estrogen involve ERα, but only estrogen regulates its cellular concentration. This is consistent with the hypothesis that bone loss associated with estrogen deficiency is a consequence of reduction in ERα number/activity associated with lower estrogen concentration reducing the effectiveness of bone cells' anabolic response to strain.
Role of the Ram Domain and Ankyrin Repeats on Notch Signaling and Activity in Cells of Osteoblastic Lineage
Authors: Deregowski Valerie , Gazzerro Elisabetta , Priest Leah , Rydziel Sheila , Canalis Ernesto 
Published: July 2006

Abstract
Notch proteins belong to a family of single pass transmembrane receptors that are activated after interactions with the membrane-bound ligands Delta and Jagged/Serrate. We determined the pathways responsible for the inhibitory effects of Notch on osteoblastogenesis and the contributions of the RAM domain and ankyrin repeats to this process in cells of the osteoblastic lineage.
Introduction: Notch receptors play a role in osteoblast differentiation. Activation of Notch results in its cleavage and the release of its intracellular domain (NICD), which interacts with the CBF1/RBP-Jκ, Suppressor of Hairless, Lag-1 (CSL) family of transcription factors. The interaction is presumably mediated by the RBP-Jκ–associated module (RAM) of NICD, although the role of the ankyrin repeats is uncertain.
Materials and Methods: To determine the contributions of the RAM domain and ankyrin repeats to the inhibitory effects of Notch on osteoblastogenesis, ST-2 and MC3T3-E1 cells were transfected or transduced with vectors expressing NICD, RAM (NICD ΔRAM), and ankyrin (NICD ΔANK) deletion mutants.
Results: Notch increased the transactivation of transiently transfected 12xCSL-Luc constructs, containing 12 repeats of an RBP-Jκ/CSL binding site, and of the hairy and E (spl) (HES)-1 promoter. Deletion of the ankyrin repeats resulted in the loss of 12xCSL-Luc and HES-1 promoter transactivation, whereas deletion of the RAM domain caused a partial loss of 12xCSL-Luc and sustained HES-1 promoter transactivation. NICD overexpression inhibited osteocalcin mRNA levels and alkaline phosphatase activity in ST-2 cells, and deletion of the ankyrin repeats, and to a lesser extent of the RAM domain, resulted in loss of the NICD inhibitory effect. NICD inhibited Wnt signaling and deletion of ankyrin repeats or the RAM domain restored Wnt signaling activity.
Conclusions: The RAM domain and ankyrin repeats are required for Notch signaling and activity, and the CSL pathway is central to the inhibitory effect of Notch on osteoblastogenesis.
A Biomechanical Analysis of the Effects of Resorption Cavities on Cancellous Bone Strength
Authors: Hernandez Christopher J , Gupta Atul , Keaveny Tony M 
Published: July 2006

Abstract
We evaluated the effects of resorption cavities on cancellous bone strength using computational methods. Adding cavities to cancellous bone caused reductions in strength and stiffness that were greater than expected from the associated changes in bone volume and more pronounced when cavities were targeted to regions of high tissue strain.
Introduction: The amount of bone turnover in the skeleton has recently been implicated as a factor influencing bone strength. One mechanism proposed to explain this effect is that resorption cavities reduce the effective thickness of trabeculae and modify local stress distributions leading to reduced mechanical performance of the entire structure. In this study, we tested the plausibility of this mechanism.
Materials and Methods: High-resolution finite element models were created from μCT images of 16 vertebral cancellous bone samples, as well as from images of the samples in which cavities had been added digitally—either at regions of high strain (targeted) or placed at random on the bone surface (nontargeted). The effect of resorption cavities on predicted bone strength and stiffness was evaluated by comparing the relationships between mechanical properties and bone volume fraction among the three groups (the original images, those with nontargeted cavities, and those with targeted cavities).
Results: Addition of resorption cavities modified the relationship between mechanical properties and bone volume fraction in the finite element models such that, for a given bone volume fraction, stiffness and yield strength were reduced compared with the original images (p &lt; 0.05). The differences in yield strength–volume fraction relationships between the original models and those with targeted cavities were significantly greater than those between the original models and those with nontargeted cavities (p &lt; 0.05). None of the differences in predicted mechanical properties per unit bone volume fraction could be accounted for by 3D measures of microarchitecture.
Conclusions: Resorption cavities may influence cancellous bone strength and stiffness independent of their effect on bone volume. The effects of cavities on bone mechanical performance relative to bone volume are greater when cavities are targeted to regions of high strain and cannot be predicted using standard microarchitecture measures.
Mineral Formation in Joints Caused by Complete or Joint-Specific Loss of ANK Function
Authors: Gurley Kyle A , Chen Hao , Guenther Catherine , Nguyen Elizabeth T , Rountree Ryan B , Schoor Michael , Kingsley David M 
Published: July 2006

Abstract
To reveal the ANK complete loss of function phenotype in mice, we generated conditional and null alleles. Mice homozygous for the null allele exhibited widespread joint mineralization, similar in severity to animals harboring the original ank allele. A delayed yet similar phenotype was observed in mice with joint-specific loss of ANK function.
Introduction: The ANK pyrophosphate regulator was originally identified and proposed to play a key role in articular cartilage maintenance based on a single spontaneous mouse mutation (ank) that causes severe generalized arthritis. A number of human mutations have subsequently been reported in the human ortholog (ANKH), some of which produce skull and long bone defects with no apparent defects in joints or articular cartilage. None of the currently known mouse or human mutations clearly eliminate the function of the endogenous gene.
Materials and Methods: Two new Ank alleles were generated using homologous recombination in mouse embryonic stem (ES) cells. Joint range of motion assays and μCT studies were used to quantitatively assess phenotypic severity in wildtype, heterozygous, and homozygous mice carrying either the null (Anknull) or original (Ankank) allele. A Gdf5-Cre expressing line was crossed to mice harboring the conditional (Ankfloxp) allele to eliminate ANK function specifically in the joints. Histological stains and β-galactosidase (LACZ) activity were used to determine the correlation between local loss of ANK function and defective joint phenotypes.
Results: Ank null /Anknull mice develop severe ectopic postnatal crystal deposition in almost every joint of the body, leading to eventual joint fusion and loss of mobility. The severity of phenotype in these mice is indistinguishable from that of Ankank/Ankank mice. In addition, despite the widespread expression of Ank in many tissues, the specific deletion of Ank in joints also produces joint mineralization and ankylosis.
Conclusions: These studies show that ANK function is required locally in joints to inhibit mineral formation and that the Ank gene plays a key role in postnatal maintenance of joint mobility and function.
Migration, Transnationalism, and Belonging: Movements in the Nation‐State
Authors: GULLETTE GREGORY S. 
Published: July 2006

Sovereign Bodies: Citizens, Migrants, and States in the Postcolonial World. Thomas Blom Hansen and Finn Stepputat, eds. Princeton: Princeton University Press, 2005. 366 pp.When Women Come First: Gender and Class in Transnational Migration. Sheba Mariam George. Berkley: University of California Press, 2005. 259 pp.In a New Land: A Comparative View of Immigration. Nancy Foner. New York: New York University Press, 2005. 327 pp.
Crossing, Creolization, and the African Roots of American Culture
Authors: OTTENHEIMER HARRIET JOSEPH 
Published: July 2006

Group Harmony: The Black Urban Roots of Rhythm and Blues. Stuart L. Goosman. Philadelphia: University of Pennsylvania Press, 2005. 291 pp.Right to Rock: The Black Rock Coalition and the Cultural Politics of Race. Maureen Mahon. Durham, NC: Duke University Press, 2004. 317 pp.Crossovers: Essays on Race, Music, and American Culture. John Szwed. Philadelphia: University of Pennsylvania Press, 2005. 283 pp.
Anthropologies of Violence and Resistance
Authors: SANFORD VICTORIA D. L. 
Published: July 2006

Encounters with Violence in Latin America: Urban Poor Perceptions from Colombia and Guatemala. Caroline O. N. Moser and Cathy McIlwaine. New York: Routledge, 2004. 272 pp.Violence: Theory and Ethnography. Pamela J. Stewart and Andrew Strathern. New York: Continuum, 2002. 196 pp.Shadows of War: Violence, Power, and International Profiteering in the Twenty‐First Century. Carolyn Nordstrom. Berkeley: University of California Press, 2004. 293 pp.
Cross‐Cultural Approaches to Adoption; Cultures of Transnational Adoption
Authors: SELIGMANN LINDA J. 
Published: July 2006

Cross‐Cultural Approaches to Adoption. Fiona Bowie, ed. New York: Routledge, 2005. 279 pp.Cultures of Transnational Adoption. Toby Alice Volkman, ed. Durham, NC: Duke University Press, 2005. 232 pp.
Genotoxicity in wood mice (Apodemus sylvaticus) along a pollution gradient: Exposure-, age-, and gender-related effects
Authors: Scheirs Jan , de Coen An , Covaci Adrian , Beernaert Joke , Kayawe Valentine Mubiana , Caturla Mercè , de Wolf Hans , Baert Philippe , Van Oostveldt Patrick , Verhagen Ron , Blust Ronny , de Coen Wim 
Published: July 2006

Abstract
We investigated the effects of environmental pollution on genetic damage in wood mice (Apodemus sylvaticus) by means of the comet assay, with special attention to the role of age and gender as potential confounding variables. The present study was carried out at four sites along a pollution gradient in the vicinity of Antwerp (Belgium), with a nonferrous smelter as the main pollution source. We measured the concentration of heavy metals (Cd, Co, Cr, Cu, Fe, Mn, Pb, and Zn) in mouse liver and kidney and the concentration of organochlorine compounds (polychlorinated biphenyls and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene) in mouse muscle tissue to assess individual exposure. Cadmium exposure was very high at the sites closest to the smelter, and exposure to this metal decreased with increasing distance from the smelter. Exposure to the other pollutants was low to moderate at the different sites. Genetic damage was higher in mice from populations in the vicinity of the nonferrous smelter compared with that in the control populations. A significant increase in genetic damage with age was observed at the most polluted sites, but not at the control sites. Genetic damage was higher in male mice than in female mice at the most polluted site, but not at the other areas. Yet, no obvious relationship was found between individual pollutant levels and individual genetic damage levels. We conclude that the comet assay can be used to compare genotoxicity at the population level if the confounding variables of gender and age are taken into account. However, its use for individual health risk assessment remains questionable.
Detection of androgenic activity in emissions from diesel fuel and biomass combustion
Authors: Owens Clyde V. , Lambright Christy , Cardon Mary , Gray L. Earl , Gullett Brian K. , Wilson Vickie S. 
Published: July 2006

Abstract
The present study evaluated both diesel fuel exhaust and biomass (wood) burn extracts for androgen receptor–mediated activity using MDA-kb2 cells, which contain an androgen-responsive promoter-luciferase reporter gene construct. This assay and analytical fractionization of the samples were used as tools to separate active from inactive fractions, with the goal of identifying the specific compounds responsible for the activity. A significant androgenic response was detected from the diesel emission. High-performance liquid chromatographic fractionation of the sample indicated that significant androgenic activity was retained in three fractions. 4-Hydroxybiphenyl was identified from the most active fraction using gas chromatography/mass spectroscopy. This purified compound was then tested at doses from 1 nM to 100 μM. 4-Hydroxybiphenol exhibited antagonist activity at low concentrations and agonist activity at high concentrations. A competitive-binding assay confirmed binding to the androgen receptor, with a median inhibitory concentration for radioligand binding of approximately 370 nM. Significant androgenic activity also was detected in the wood burn samples, but we were unable to identify the specific chemicals responsible for this endocrine activity. The present study demonstrates that in vitro bioassays can serve as sensitive bioanalytical tools to aid in characterization of complex environmental mixtures.
Combined effects of a herbicide (atrazine) and predation on the life history of a pond snail, Physa gyrina
Authors: Sandland Gregory J. , Carmosini Nadia 
Published: July 2006

Abstract
We investigated the combined effects of chronic pesticide exposure and predation on the life-history traits of Physa gyrina. Results show that atrazine and predation can impact snail immune function, reproduction, and survival. This work emphasizes the need to assess sublethal life-history responses to multiple stressors over biologically relevant timescales.
Evaluation of the methoxytriazine herbicide prometon using a short-term fathead minnow reproduction test and a suite of in vitro bioassays
Authors: Villeneuve Daniel L. , Murphy Margaret B. , Kahl Michael D. , Jensen Kathleen M. , Butterworth Brian C. , Makynen Elizabeth A. , Durhan Elizabeth J. , Linnum Ann , Leino Richard L. , Curtis Lawrence R. , Giesy John P. , Ankley Gerald T. 
Published: July 2006

AbstractPrometon is one of the most consistently detected herbicides in the U.S. environment. However, no previous assessment of the potential for prometon or related methoxytriazine herbicides to act as endocrine-disrupting chemicals has been conducted. This study used an array of in vitro bioassays to assess whether prometon, atraton, terbumeton, or secbumeton might act as potent (ant)agonists of the aryl hydrocarbon, estrogen, androgen, or glucocorticoid receptors or as aromatase inhibitors or inducers in vitro. Potential effects of prometon were also evaluated using a 21-d fathead minnow reproduction assay. Concentrations of methoxytriazines, as great as 1 mg/L (4.4 μM), did not induce significant dioxin-like responses in H4IIE-luc cells, estrogenic responses in MVLN cells, or androgen or glucocorticoid receptor–mediated responses in MDA-kb2 cells, nor did the methoxytriazines significantly affect aromatase activity in vitro. In the fathead minnow assay, exposure to 20, 200, or 1,000 μg prometon/L significantly reduced the weight of the male fat pad (an androgen-responsive tissue) relative to body weight. Exposure to 20 μg prometon/L significantly increased female plasma testosterone concentrations, but the effect was not observed at greater concentrations. Overall, prometon did not significantly reduce fecundity over the 21-d exposure, nor were other endpoints, including plasma vitellogenin and estradiol concentrations, brain and ovary aromatase activity, and male tubercle index, significantly affected. Evidence from our work suggests that prometon may cause subtle endocrine and/or reproductive effects in fathead minnows, but no clear mechanism of action was observed. The relevance of these effects to hazard assessment for the pesticide is uncertain.