bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nell-1, a key functional mediator of Runx2, partially rescues calvarial defects in Runx2
+/− mice
Authors: Zhang Xinli , Ting Kang , Bessette Catherine M , Culiat Cymbeline T , Sung Sang Jin , Lee Haofu , Chen Feng , Shen Jia , Wang James J , Kuroda Shun'ichi , Soo Chia 
Published: October 2010

Abstract
Mesenchymal stem cell commitment to an osteoprogenitor lineage requires the activity of Runx2, a molecule implicated in the etiopathology of multiple congenital craniofacial anomalies. Through promoter analyses, we have recently identified a new direct transcriptional target of Runx2, Nell-1, a craniosynostosis (CS)–associated molecule with potent osteogenic properties. This study investigated the mechanistic and functional relationship between Nell-1 and Runx2 in regulating osteoblast differentiation. The results showed that spatiotemporal distribution and expression levels of Nell-1 correlated closely with those of endogenous Runx2 during craniofacial development. Phenotypically, cross-mating Nell-1 overexpression transgenic (CMV-Nell-1) mice with Runx2 haploinsufficient (Runx2+/−) mice partially rescued the calvarial defects in the cleidocranial dysplasia (CCD)–like phenotype of Runx2+/− mice, whereas Nell-1 protein induced mineralization and bone formation in Runx2+/− but not Runx2−/− calvarial explants. Runx2-mediated osteoblastic gene expression and/or mineralization was severely reduced by Nell-1 siRNA oligos transfection into Runx2+/+ newborn mouse calvarial cells (NMCCs) or in N-ethyl-N-nitrosourea (ENU)–induced Nell-1−/− NMCCs. Meanwhile, Nell-1 overexpression partially rescued osteoblastic gene expression but not mineralization in Runx2 null (Runx2−/−) NMCCs. Mechanistically, irrespective of Runx2 genotype, Nell-1 signaling activates ERK1/2 and JNK1 mitogen-activated protein kinase (MAPK) pathways in NMCCs and enhances Runx2 phosphorylation and activity when Runx2 is present. Collectively, these data demonstrate that Nell-1 is a critical downstream Runx2 functional mediator insofar as Runx2-regulated Nell-1 promotes osteoblastic differentiation through, in part, activation of MAPK and enhanced phosphorylation of Runx2, and Runx2 activity is significantly reduced when Nell-1 is blocked or absent. © 2011 American Society for Bone and Mineral Research.
Interleukin-33 is expressed in differentiated osteoblasts and blocks osteoclast formation from bone marrow precursor cells
Authors: Schulze Jochen , Bickert Thomas , Beil F Timo , Zaiss Mario M , Albers Joachim , Wintges Kristofer , Streichert Thomas , Klaetschke Kristin , Keller Johannes , Hissnauer Tim-Nicolas , Spiro Alexander S , Gessner Andre , Schett Georg , Amling Michael , McKenzie Andrew NJ , Horst Andrea Kristina , Schinke Thorsten 
Published: October 2010

Abstract
Since the hematopoetic system is located within the bone marrow, it is not surprising that recent evidence has demonstrated the existence of molecular interactions between bone and immune cells. While interleukin 1 (IL-1) and IL-18, two cytokines of the IL-1 family, have been shown to regulate differentiation and activity of bone cells, the role of IL-33, another IL-1 family member, has not been addressed yet. Since we observed that the expression of IL-33 increases during osteoblast differentiation, we analyzed its possible influence on bone formation and observed that IL-33 did not affect matrix mineralization but enhanced the expression of Tnfsf11, the gene encoding RANKL. This finding led us to analyze the skeletal phenotype of Il1rl1-deficient mice, which lack the IL-33 receptor ST2. Unexpectedly, these mice displayed normal bone formation but increased bone resorption, thereby resulting in low trabecular bone mass. Since this finding suggested a negative influence of IL-33 on osteoclastogenesis, we next analyzed osteoclast differentiation from bone marrow precursor cells and observed that IL-33 completely abolished the generation of TRACP+ multinucleated osteoclasts, even in the presence of RANKL and macrophage colony-stimulating factor (M-CSF). Although our molecular studies revealed that IL-33 treatment of bone marrow cells caused a shift toward other hematopoetic lineages, we further observed a direct negative influence of IL-33 on the osteoclastogenic differentiation of RAW264.7 macrophages, where IL-33 repressed the expression of Nfatc1, which encodes one of the key transciption factors of osteoclast differentiation. Taken together, these findings have uncovered a previously unknown function of IL-33 as an inhibitor of bone resorption. © 2011 American Society for Bone and Mineral Research.
In vivo discrimination of hip fracture with quantitative computed tomography: Results from the prospective European Femur Fracture Study (EFFECT)
Authors: Bousson Valérie Danielle , Adams Judith , Engelke Klaus , Aout Mounir , Cohen-Solal Martine , Bergot Catherine , Haguenauer Didier , Goldberg Daniele , Champion Karine , Aksouh Redha , Vicaut Eric , Laredo Jean-Denis 
Published: October 2010

Abstract
In assessing osteoporotic fractures of the proximal femur, the main objective of this in vivo case-control study was to evaluate the performance of quantitative computed tomography (QCT) and a dedicated 3D image analysis tool [Medical Image Analysis Framework—Femur option (MIAF-Femur)] in differentiating hip fracture and non–hip fracture subjects. One-hundred and seven women were recruited in the study, 47 women (mean age 81.6 years) with low-energy hip fractures and 60 female non–hip fracture control subjects (mean age 73.4 years). Bone mineral density (BMD) and geometric variables of cortical and trabecular bone in the femoral head and neck, trochanteric, and intertrochanteric regions and proximal shaft were assessed using QCT and MIAF-Femur. Areal BMD (aBMD) was assessed using dual-energy X-ray absorptiometry (DXA) in 96 (37 hip fracture and 59 non–hip fracture subjects) of the 107 patients. Logistic regressions were computed to extract the best discriminates of hip fracture, and area under the receiver characteristic operating curve (AUC) was calculated. Three logistic models that discriminated the occurrence of hip fracture with QCT variables were obtained (AUC = 0.84). All three models combined one densitometric variable—a trabecular BMD (measured in the femoral head or in the trochanteric region)—and one geometric variable—a cortical thickness value (measured in the femoral neck or proximal shaft). The best discriminant using DXA variables was obtained with total femur aBMD (AUC = 0.80, p = .003). Results highlight a synergistic contribution of trabecular and cortical components in hip fracture risk and the utility of assessing QCT BMD of the femoral head for improved understanding and possible insights into prevention of hip fractures. © 2011 American Society for Bone and Mineral Research.
EP1−/− mice have enhanced osteoblast differentiation and accelerated fracture repair
Authors: Zhang Minjie , Ho Hsin-chiu , Sheu Tzong-jen , Breyer Matthew D , Flick Lisa M , Jonason Jennifer H , Awad Hani A , Schwarz Edward M , O'Keefe Regis J 
Published: October 2010

Abstract
As a downstream product of cyclooxygenase 2 (COX-2), prostaglandin E2 (PGE2) plays a crucial role in the regulation of bone formation. It has four different receptor subtypes (EP1 through EP4), each of which exerts different effects in bone. EP2 and EP4 induce bone formation through the protein kinase A (PKA) pathway, whereas EP3 inhibits bone formation in vitro. However, the effect of EP1 receptor signaling during bone formation remains unclear. Closed, stabilized femoral fractures were created in mice with EP1 receptor loss of function at 10 weeks of age. Healing was evaluated by radiographic imaging, histology, gene expression studies, micro–computed tomographic (µCT), and biomechanical measures. EP1−/− mouse fractures have increased formation of cartilage, increased fracture callus, and more rapid completion of endochondral ossification. The fractures heal faster and with earlier fracture callus mineralization with an altered expression of genes involved in bone repair and remodeling. Fractures in EP1−/− mice also had an earlier appearance of tartrate-resistant acid phosphatase (TRAcP)–positive osteoclasts, accelerated bone remodeling, and an earlier return to normal bone morphometry. EP1−/− mesenchymal progenitor cells isolated from bone marrow have higher osteoblast differentiation capacity and accelerated bone nodule formation and mineralization in vitro. Loss of the EP1 receptor did not affect EP2 or EP4 signaling, suggesting that EP1 and its downstream signaling targets directly regulate fracture healing. We show that unlike the PGE2 receptors EP2 and EP4, the EP1 receptor is a negative regulator that acts at multiple stages of the fracture healing process. Inhibition of EP1 signaling is a potential means to enhance fracture healing. © 2011 American Society for Bone and Mineral Research.
The relationship between bisphosphonate adherence and fracture: Is it the behavior or the medication? Results from the placebo arm of the fracture intervention trial
Authors: Curtis Jeffrey R , Delzell Elizabeth , Chen Lang , Black Dennis , Ensrud Kristine , Judd Suzanne , Safford Monika M , Schwartz Ann V , Bauer Douglas C 
Published: October 2010

Abstract
Medication compliance may be a surrogate for factors that improve health outcomes such as fractures. Little is known about the size of this potential “healthy adherer” effect. We evaluated the hypothesis that compliance with placebo is associated inversely with bone loss and fractures among women participating in the Fracture Intervention Trial (FIT). Compliance with placebo and alendronate was evaluated using daily medication diaries. Women were defined as having high compliance if they took 80% or more of dispensed study medication. Change in bone mineral density (BMD) was assessed using mixed models comparing women with high versus lower compliance with placebo. Cox proportional-hazards models analyzed the association between placebo compliance and various types of fractures. Among 3169 women randomized to placebo, 82% had high compliance. Compared with women with lower placebo compliance, bone loss at the total hip was lower in compliant placebo-treated women (−0.43%/year versus −0.58%/year, p = .04). Among placebo-treated women, there were 46 hip, 110 wrist, 77 clinical vertebral, and 492 total clinical fractures. Compared with women with lower placebo compliance, women with high placebo compliance had a nonsignificant reduced risk for hip fracture [adjusted hazard ratio (HR) = 0.67, 95% confidence interval (CI) 0.30–1.45]. This trend was not observed for other fractures. Medication compliance may be a proxy for factors that confers benefit on reducing hip fracture (but not other types of fractures) independent of the effect of the medication itself. Nonrandomized studies of interventions designed to maintain or improve bone density and/or hip fracture may need to consider medication compliance as a confounder to better estimate true intervention effects. © 2011 American Society for Bone and Mineral Research.
Anti-FGF-23 neutralizing antibodies ameliorate muscle weakness and decreased spontaneous movement of Hyp mice
Authors: Aono Yukiko , Hasegawa Hisashi , Yamazaki Yuji , Shimada Takashi , Fujita Toshiro , Yamashita Takeyoshi , Fukumoto Seiji 
Published: October 2010

Abstract
Fibroblast growth factor 23 (FGF-23) plays causative roles in the development of several hypophosphatemic rickets/osteomalacia such as X-linked hypophosphatemic rickets/osteomalacia (XLH) and tumor-induced rickets/osteomalacia. Patients with hypophosphatemic rickets/osteomalacia often complain of muscle weakness and bone pain that severely affect daily activities of these patients. The purpose of this study was to examine whether anti-FGF-23 antibodies, which have been shown to improve hypophosphatemia and rachitic changes of juvenile Hyp mice in a murine model of XLH, also ameliorate hypophosphatemic osteomalacia and affect muscle force and spontaneous motor activity in adult Hyp mice. Repeated injections of anti-FGF-23 antibodies increased serum phosphate and 1,25-dihydroxyvitmain D levels and enhanced mineralization of osteoid in adult Hyp mice, whereas bone length did not change. We found that grip strength was weaker and that spontaneous movement was less in adult Hyp mice than in wild-type mice. In addition, FGF-23 antibodies increased grip strength and spontaneous movement. These results suggest that the inhibition of excess FGF-23 action not only ameliorates hypophosphatemia and impaired mineralization of bone but also improves muscle weakness and daily activities of patients with FGF-23-related hypophosphatemic rickets/osteomalacia. © 2011 American Society for Bone and Mineral Research.
Breast tumors induced by N-methyl-N-nitrosourea are damaging to bone strength, structure, and mineralization in the absence of metastasis in rats
Authors: Thorpe Matthew P , Valentine Rudy J , Moulton Christopher J , Wagoner Johnson Amy J , Evans Ellen M , Layman Donald K 
Published: October 2010

Abstract
Current theory on the influence of breast cancer on bone describes metastasis of tumor cells to bone tissue, followed by induction of osteoclasts and bone degradation. Tumor influences on bone health in pre- or nonmetastatic models are unknown. Female rats (n = 48, 52 days old) were injected with N-methyl-N-nitrosourea (MNU) to induce breast cancer. Animals were euthanized 10 weeks later, and tumors were weighed and classified histologically. Right femurs were extracted for testing of bone mineral density (BMD) by dual X-ray absorptiometry (DXA), bone mechanical strength by three-point bending and femoral neck bending tests, and structure by micro–computed tomography (µCT). Of 48 rats, 22 developed one or more tumors in response to MNU injection by 10 weeks. Presence of any tumor predicted significantly poorer bone health in 17 of 28 measures. In tumored versus nontumored animals, BMD was adversely affected by 3%, force at failure of the femoral midshaft by 4%, force at failure of the femoral neck by 12%, and various trabecular structural parameters by 6% to 27% (all p &lt; .05). Similarly, greater tumor burden, represented by total tumor weight, adversely correlated with bone outcomes: r = −0.51 for BMD, −0.42 and −0.35 for femur midshaft force and work at failure, and between 0.36 and 0.59 (absolute values) for trabecular architecture (all p &lt; .05). Presence of MNU-induced tumors and total tumor burden showed a negative association with bone health of the femur in rats in the absence of metastasis. Further study is required to elucidate mechanisms for this association. © 2011 American Society for Bone and Mineral Research.
Development and Evaluation of the Social Anxiety and Depression Life Interference‐24 (SADLI‐24) Inventory
Authors: Osman Augustine , Bagge Courtney L. , Freedenthal Stacey , Gutierrez Peter M. , Emmerich Ashley 
Published: October 2010

AbstractWe describe the development of a new self‐report instrument, the Social Anxiety and Depression Life Interference‐24 (SADLI‐24) inventory. We initially retained 30 content specific items for the instrument (Study 1). In Study 2 (N = 438), we established a 2‐factor solution, Social Anxiety Life Interference‐12 (SALI‐12) and Depression Life Interference‐12 (DLI‐12). We also examined estimates of known‐groups and concurrent validity. Confirmatory factor analysis in Study 3 (N = 430) provided support for the oblique two‐factor structure. In Study 4 (N = 179), we provided additional support for estimates of known‐groups validity. In Study 5 (N = 63), we evaluated estimates of test‐retest reliability. Both SADLI‐24 scale scores showed good estimates of internal consistency. © 2010 Wiley Periodicals, Inc. J Clin Psychol 67:1–17, 2010.
Insomnia treatments: moving from efficacy to effectiveness
Authors: Haynes Patricia L. , Bootzin Richard R. 
Published: October 2010

AbstractThis issue of the Journal of Clinical Psychology: In Session focuses on the treatment of insomnia and sleep disturbances in a variety of populations. Over the past decade, there has been an increased recognition of the importance of sleep to health and well‐being. Despite this recognition, there continues to be a shortage of practitioners with experience in insomnia therapies. In this article, the authors identify and refute commonly held myths that might hinder the treatment of sleep problems. They conclude by introducing the seven articles that constitute this special issue. © 2010 Wiley Periodicals, Inc. J Clin Psychol: In Session 66:1–6, 2010.
Preferences for relational style with mental health clinicians: A qualitative comparison of African American, Latino and Non‐Latino White patients
Authors: Mulvaney‐Day Norah E. , Earl Tara R. , Diaz‐Linhart Yaminette , Alegría Margarita 
Published: October 2010

AbstractThe goal of this study is to analyze preferences for relational styles in encounters with mental health providers across racial and ethnic groups. Four primary themes describe what patients want from a mental health provider: listening, understanding, spending time, and managing differences. However, using contextual comparative analysis, the findings explicate how these themes are described differently across African Americans, Latinos, and non‐Latino Whites, uncovering important qualitative differences in the meaning of these themes across the groups. The article suggests that closer attention to qualitative preferences for style of interaction with providers may help address disparities in mental health care for racial and ethnic minorities. © 2010 Wiley Periodicals, Inc. J Clin Psychol 67:1–14, 2010.
The formation of the nervous system during larval development in Triops cancriformis (Bosc) (crustacea, Branchiopoda): An immunohistochemical survey
Authors: Fritsch Martin , Richter Stefan 
Published: October 2010

AbstractWe provide data of the development of thenervous system during the first five larval stages of Triops cancriformis. We use immunohistochemical labeling (against acetylated α‐tubulin, serotonin, histamine, and FMRFamide), confocal laser scanning microscopy analysis, and 3D‐reconstruction. The development of the nervous system corresponds with the general anamorphic development in T. cancriformis. In larval stage I (L I), all brain parts (proto‐, deuto‐, and tritocerebrum), the circumoral connectives, and the mandibular neuromere are already present. Also, the frontal filaments and the developing nauplius eye are already present. However, until stage L III, the nauplius eye only consists of three cups. Throughout larval development, the protocerebral network differentiates into distinct subdivisions. In the postnaupliar region, additional neuromeres and their commissures emerge in an anteroposterior gradient. The larval nervous system in L V consists of a differentiated protocerebrum including a central body, a nauplius eye comprising four cups, a circumoral nerve ring, mandibular‐ and postnaupliar neuromeres up to the seventh thoracic segment, each featuring an anterior and a posterior commissure, and two parallel connectives. The presence of a protocerebral bridge is questionable. The distribution of neurotransmitters in L I is restricted to the naupliar nervous system. Over the course of the five stages of development, neurotransmitter distribution also follows an anteroposterior gradient. Each neuromere is equipped with two ganglia innervating the locomotional appendages and possesses a specific neurotransmitter distribution pattern. We suggest a correlation between neurotransmitter expression and locomotion. J. Morphol., 2010. © 2010 Wiley‐Liss, Inc.
Person–organization and person–supervisor fits: Employee commitments in a Chinese context
Authors: van Vianen Annelies E.M. , Shen Chi‐Tai , Chuang Aichia 
Published: October 2010

AbstractThe present study simultaneously examined people's perceptions of person–organization (PO) and person–supervisor (PS) fit and related these perceptions to employees' commitments. Three‐hundred‐and‐sixty employee–supervisor dyads from Taiwanese organizations reported about their PO fit and PS fit perceptions. In addition, supervisors reported about their perceptions of fit and guanxi with each of their employees. Results indicated that PO and PS fit perceptions both had an independent and additive relationship with organizational commitment. The link between employee PS fit perceptions and organizational commitment was mediated by commitment to the supervisor. Both employee and supervisor fit perceptions contributed to commitment to the supervisor through their influence on the quality of the leader‐member exchange (LMX). Guanxi could not explain additional variance in LMX and supervisor commitment. Implications for theory and practices regarding person–environment fit, commitment, and LMX are discussed. The study findings offered suggestions for a new Theory of Multiple Fits. Copyright © 2010 John Wiley & Sons, Ltd.
A multilevel study of the relationships between diversity training, ethnic discrimination and satisfaction in organizations
Authors: King Eden B. , Dawson Jeremy F. , Kravitz David A. , Gulick Lisa M. V. 
Published: October 2010

SummaryThe prevalence of diversity training has not been matched by empirical research on its effectiveness. Among the most notable gaps are an absence of attention to its impact on discrimination and limited consideration of organizational‐level factors. Results from employee surveys across 395 healthcare organizations reveal an effect of the extent of diversity training in organizations on ethnic minorities' experiences of discrimination. In addition, the results demonstrate that the consequences of ethnic discrimination for individuals' job attitudes are influenced by organizational‐level phenomenon. These findings highlight the importance of attending to ethnic discrimination as an outcome of diversity training with implications for employee attitudes. Copyright © 2010 John Wiley & Sons, Ltd.
Cumulative effects of hypercholesterolemia on tendon biomechanics in a mouse model
Authors: Beason David P. , Abboud Joseph A. , Kuntz Andrew F. , Bassora Rocco , Soslowsky Louis J. 
Published: October 2010

AbstractHigh cholesterol represents a significant healthcare problem. Clinical studies have linked hypercholesterolemia to Achilles tendon xanthomas and rotator cuff tears, and research in other systems indicates detrimental effects of high cholesterol; however, understanding of its impact on tendon properties and healing is limited. We hypothesized that tendons from aging hypercholesterolemic (APOE) mice would exhibit inferior baseline and healing mechanical properties compared to controls, while younger, but mature mice would be no different. Surprisingly, tensile testing of patellar tendons from 14‐week‐old APOE mice receiving a unilateral full‐thickness central defect resulted in normalized (injured:sham) cross‐sectional areas closer to baseline (p = 0.02) compared to controls. Uninjured data from 10‐month‐old APOE mice showed a decrease in elastic modulus (p = 0.02), indicating a detrimental effect of hypercholesterolemia on tendon properties in this model. These results could benefit patients through knowledge that high cholesterol could increase the likelihood of tendon tears. Furthermore, knowledge that tendon tears are indicative of high cholesterol could provide orthopedic clinicians with an additional preventive treatment opportunity for patients with undiagnosed hypercholesterolemia. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:380–383, 2011