bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrochemical Codeposition of Mg–Li Alloys from a Molten KCl–LiCl–MgCl2 System
Authors: Yan Yongde , Zhang Milin , Han Wei , Xue Yun , Cao Dianxue , Yuan Yi 
Published: February 2008

Abstract
This work presents a novel study on electrochemical codeposition of Mg–Li alloys on molybdenum in KCl–LiCl (50:50 wt %) melts containing different concentrations MgCl2 at 943 K. Cyclic voltammograms showed that the underpotential deposition (UPD) of lithium on pre-deposited magnesium leads to the formation of liquid Mg–Li alloys. The codepositon of Mg and Li happens when the current intensity exceeds 0.59 A cm−2 in KCl–LiCl melts containing 5 wt % MgCl2. α, α + β, and β phases Mg–Li alloys with different lithium contents were obtained by galvanostatic electrolysis from KCl–LiCl melts with different concentrations MgCl2.
Face processing in different brain areas, and critical band masking
Authors: Rolls Edmund T. 
Published: February 2008

Neurophysiological evidence is described showing that some neurons in the macaque inferior temporal visual cortex have responses that are invariant with respect to the position, size, view, and spatial frequency of faces and objects, and that these neurons show rapid processing and rapid learning. Critical band spatial frequency masking is shown to be a property of these face‐selective neurons and of the human visual perception of faces. Which face or object is present is encoded using a distributed representation in which each neuron conveys independent information in its firing rate, with little information evident in the relative time of firing of different neurons. This ensemble encoding has the advantages of maximizing the information in the representation useful for discrimination between stimuli using a simple weighted sum of the neuronal firing by the receiving neurons, generalization, and graceful degradation. These invariant representations are ideally suited to provide the inputs to brain regions such as the orbitofrontal cortex and amygdala that learn the reinforcement associations of an individual's face, for then the learning, and the appropriate social and emotional responses generalize to other views of the same face. A theory is described of how such invariant representations may be produced by self‐organizing learning in a hierarchically organized set of visual cortical areas with convergent connectivity. The theory utilizes either temporal or spatial continuity with an associative synaptic modification rule. Another population of neurons in the cortex in the superior temporal sulcus encodes other aspects of faces such as face expression, eye‐gaze, face view, and whether the head is moving. These neurons thus provide important additional inputs to parts of the brain such as the orbitofrontal cortex and amygdala that are involved in social communication and emotional behaviour.Outputs of these systems reach the amygdala, in which face‐selective neurons are found, and also the orbitofrontal cortex, in which some neurons are tuned to face identity and others to face expression. In humans, activation of the orbitofrontal cortex is found when a change of face expression acts as a social signal that behaviour should change; and damage to the human orbitofrontal and pregenual cingulate cortex can impair face and voice expression identification, and also the reversal of emotional behaviour that normally occurs when reinforcers are reversed.
Bone Formation During Distraction Osteogenesis Is Dependent on Both VEGFR1 and VEGFR2 Signaling
Authors: Jacobsen Kimberly A , Al-Aql Zainab S , Wan Chao , Fitch Jennifer L , Stapleton Stephanie N , Mason Zachary D , Cole Robert M , Gilbert Shawn R , Clemens Thomas L , Morgan Elise F , Einhorn Thomas A , Gerstenfeld Louis C 
Published: February 2008

Abstract
Introduction: Distraction osteogenesis (DO) is characterized by the induction of highly vascularized new bone formation through an intramembranous process largely devoid of the formation of cartilage.
Materials and Methods: To test the hypothesis that DO is strictly dependent on vascualrization, we inhibited vascular endothelial growth factor (VEGF) activity by antibody blockade of both receptors VEGFR1 (Flt-1) and VEGFR2 (Flk-1) or only VEGFR2 (Flk-1) in a previously developed murine tibia DO model. During normal DO, VEGFR1 (Flt-1), VEGFR2 (Flk-1), VEGFR3 (Flt4) and all four VEGF ligand (A, B, C, and D) mRNAs are induced.
Results: The expression of mRNA for the receptors generally paralleled those of the ligands during the period of active distraction. Bone formation, as assessed by μCT, showed a significant decrease with the double antibody treatment and a smaller decrease with single antibody treatment. Vessel volume, number, and connectivity showed progressive and significant inhibition in all of these of parameters between the single and double antibody blockade. Molecular analysis showed significant inhibition in skeletal cell development with the single and double antibody blockade of both VEGFR1 and 2. Interestingly, the single antibody treatment led to selective early development of chondrogenesis, whereas the double antibody treatment led to a failure of both osteogenesis and chondrogenesis.
Conclusions: Both VEGFR1 and VEGFR2 are functionally essential in blood vessel and bone formation during DO and are needed to promote osteogenic over chondrogenic lineage progression.
Bone Mass Is Preserved and Cancellous Architecture Altered Due to Cyclic Loading of the Mouse Tibia After Orchidectomy
Authors: Fritton J Christopher , Myers Elizabeth R , Wright Timothy M , van der Meulen Marjolein CH 
Published: February 2008

Abstract
Introduction: The study of adaptation to mechanical loading under osteopenic conditions is relevant to the development of osteoporotic fracture prevention strategies. We previously showed that loading increased cancellous bone volume fraction and trabecular thickness in normal male mice. In this study, we tested the hypothesis that cyclic mechanical loading of the mouse tibia inhibits orchidectomy (ORX)-associated cancellous bone loss.
Materials and Methods: Ten-week-old male C57BL/6 mice had in vivo cyclic axial compressive loads applied to one tibia every day, 5 d/wk, for 6 wk after ORX or sham operation. Adaptation of proximal cancellous and diaphyseal cortical bone was characterized by μCT and dynamic histomorphometry. Comparisons were made between loaded and nonloaded contralateral limbs and between the limbs of ORX (n = 10), sham (n = 11), and basal (n = 12) groups and tested by two-factor ANOVA with interaction.
Results: Cyclic loading inhibited bone loss after ORX, maintaining absolute bone mass at age-matched sham levels. Relative to sham, ORX resulted in significant loss of cancellous bone volume fraction (−78%) and trabecular number (−35%), increased trabecular separation (67%), no change in trabecular thickness, and smaller loss of diaphyseal cortical properties, consistent with other studies. Proximal cancellous bone volume fraction was greater with loading (ORX: 290%, sham: 68%) than in contralateral nonloaded tibias. Furthermore, trabeculae thickened with loading (ORX: 108%, sham: 48%). Dynamic cancellous bone histomorphometry indicated that loading was associated with greater mineral apposition rates (ORX: 32%, sham: 12%) and smaller percent mineralizing surfaces (ORX: −47%, sham: −39%) in the final week. Loading resulted in greater BMC (ORX: 21%, sham: 15%) and maximum moment of inertia (ORX: 39%, sham: 24%) at the cortical midshaft.
Conclusions: This study shows that cancellous bone mass loss can be prevented by mechanical loading after hormonal compromise and supports further exploration of nonpharmacologic measures to prevent rapid-onset osteopenia and associated fractures.
In Vivo Genome-Wide Expression Study on Human Circulating B Cells Suggests a NovelESR1andMAPK3Network for Postmenopausal Osteoporosis
Authors: Xiao Peng , Chen Yuan , Jiang Hui , Liu Yao-Zhong , Pan Feng , Yang Tie-Lin , Tang Zi-Hui , Larsen Jennifer A , Lappe Joan M , Recker Robert R , Deng Hong-Wen 
Published: February 2008

AbstractIntroduction: Osteoporosis is characterized by low BMD. Studies have shown that B cells may participate in osteoclastogenesis through expression of osteoclast-related factors, such as RANKL, transforming growth factor β (TGFB), and osteoprotegerin (OPG). However, the in vivo significance of B cells in human bone metabolism and osteoporosis is still largely unknown, particularly at the systematic gene expression level.Materials and Methods: In this study, Affymetrix HG-U133A GeneChip arrays were used to identify genes differentially expressed in B cells between 10 low and 10 high BMD postmenopausal women. Significance of differential expression was tested by t-test and adjusted for multiple testing with the Benjamini and Hochberg (BH) procedure (adjusted p ≤ 0.05).Results: Twenty-nine genes were downregulated in the low versus high BMD group. These genes were further analyzed using Ingenuity Pathways Analysis (Ingenuity Systems). A network involving estrogen receptor 1 (ESR1) and mitogen activated protein kinase 3 (MAPK3) was identified. Real-time RT-PCR confirmed differential expression of eight genes, including ESR1, MAPK3, methyl CpG binding protein 2 (MECP2), proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1), Scr-like-adaptor (SLA), serine/threonine kinase 11 (STK11), WNK lysine-deficient protein kinase 1 (WNK1), and zinc finger protein 446 (ZNF446).Conclusions: This is the first in vivo genome-wide expression study on human B cells in relation to osteoporosis. Our results highlight the significance of B cells in the etiology of osteoporosis and suggest a novel mechanism for postmenopausal osteoporosis (i.e., that downregulation of ESR1 and MAPK3 in B cells regulates secretion of factors, leading to increased osteoclastogenesis or decreased osteoblastogenesis).
Doubly Truncated FosB Isoform (Δ2ΔFosB) Induces Osteosclerosis in Transgenic Mice and Modulates Expression and Phosphorylation of Smads in Osteoblasts Independent of Intrinsic AP-1 Activity
Authors: Sabatakos George , Rowe Glenn C , Kveiborg Marie , Wu Meilin , Neff Lynn , Chiusaroli Riccardo , Philbrick William M , Baron Roland 
Published: February 2008

Abstract
Introduction: Activator protein (AP)-1 family members play important roles in the development and maintenance of the adult skeleton. Transgenic mice that overexpress the naturally occurring ΔFosB splice variant of FosB develop severe osteosclerosis. Translation of Δfosb mRNA produces both ΔFosB and a further truncated isoform (Δ2ΔFosB) that lacks known transactivation domains but, like ΔFosB, induces increased expression of osteoblast marker genes.
Materials and Methods: To test Δ2ΔFosB's ability to induce bone formation in vivo, we generated transgenic mice that overexpress only Δ2ΔFosB using the enolase 2 (ENO2) promoter-driven bitransgenic Tet-Off system.
Results: Despite Δ2ΔFosB's failure to induce transcription of an AP-1 reporter gene, the transgenic mice exhibited both the bone and the fat phenotypes seen in the ENO2-ΔFosB mice. Both ΔFosB and Δ2ΔFosB activated the BMP-responsive Xvent-luc reporter gene and increased Smad1 expression. Δ2ΔFosB enhanced BMP-induced Smad1 phosphorylation and the translocation of phospho-Smad1 (pSmad1) to the nucleus more efficiently than ΔFosB and showed a reduced induction of inhibitory Smad6 expression.
Conclusions: ΔFosB's AP-1 transactivating function is not needed to induce increased bone formation, and Δ2ΔFosB may act, at least in part, by increasing Smad1 expression, phosphorylation, and translocation to the nucleus.
OPG and sRANKL Serum Concentrations in Osteopenic, Postmenopausal Women After 2-Year Genistein Administration
Authors: Marini Herbert , Minutoli Letteria , Polito Francesca , Bitto Alessandra , Altavilla Domenica , Atteritano Marco , Gaudio Agostino , Mazzaferro Susanna , Frisina Alessia , Frisina Nicola , Lubrano Carla , Bonaiuto Michele , D'Anna Rosario , Cannata Maria Letizia , Corrado Francesco , Cancellieri Francesco , Faraci Marianna , Marini Rolando , Adamo Elena Bianca , Wilson Steven , Squadrito Francesco 
Published: February 2008

Abstract
Introduction: RANKL and its decoy receptor osteoprotegerin (OPG) constitute a complex physiological mediator system involved in the regulation of bone resorption and may be responsible for the homeostatic mechanism of normal bone remodeling. Genistein, an isoflavone representing 1–5% of total phytoestrogen content in soybean products, may positively regulate cellular bone metabolism, but its mechanism of action on bone is not yet fully understood.
Materials and Methods: We studied the serum levels of both soluble RANKL (sRANKL) and OPG and the sRANKL/OPG ratio in 389 postmenopausal women (age, 49–67 yr) with a femoral neck BMD &lt;0.795 g/cm2 and no significant comorbid conditions after 24-mo therapy with genistein, (n = 198; 54 mg/d) or placebo (n = 191). Both intervention and placebo contained calcium and vitamin D3. All patients received dietary instruction in an isocaloric fat-reduced diet.
Results: In comparison with placebo, sRANKL level was lower (p &lt; 0.001 versus placebo) and OPG higher in genistein recipients (p &lt; 0.001 versus placebo) at 1 and 2 yr, respectively. Moreover, at the end of 24 mo, genistein produced a significant reduction in the sRANKL/OPG ratio compared with placebo (genistein = −0.021, 95% CI, −0.020 to −0.022; placebo = +0.004, 95% CI, 0.003–0.005; difference = −0.020, 95% CI, −0.015 to −0.025, p &lt; 0.001).
Conclusions: Our findings suggest that genistein plus calcium and vitamin D3 as part of a healthy diet is able to positively modulate bone turnover in a cohort of osteopenic, postmenopausal women and improve sRANKL-OPG balance after 24 mo of treatment.
Cortical Bone Loss in Androgen-Deficient Aged Male Rats Is Mainly Caused by Increased Endocortical Bone Remodeling
Authors: Reim Natascha S , Breig Bianca , Stahr Kerstin , Eberle Johannes , Hoeflich Andreas , Wolf Eckhard , Erben Reinhold G 
Published: February 2008

Abstract
Introduction: Hypogonadism is considered to be one of the major risk factors for osteoporosis in men. Here, we sequentially studied the effects of androgen deficiency on cortical bone in aged orchiectomy (ORX) rats.
Materials and Methods: One hundred seventy 13-mo-old male Fischer-344 rats were either ORX or sham-operated. After in vivo fluorochrome labeling, groups of 8–15 SHAM and ORX rats each were killed at 2 wk and 1, 2, 3, 4, 6, and 9 mo after surgery. To examine the effects of testosterone replacement therapy, 9-mo-old ORX rats were supplemented with testosterone undecanoate at a weekly dose of 6 mg/kg for 4 mo. Cortical bone changes in the tibial shaft were monitored by pQCT analysis and by bone histomorphometry.
Results: SHAM rats did not show age-related bone loss at the tibial diaphysis. pQCT analysis and bone histomorphometry showed cortical bone osteopenia in ORX rats, beginning from 2 mo after surgery until the end of the study. Androgen deficiency induced a sustained decrease in periosteal bone formation during the first 4 mo after ORX. However, although periosteal expansion of the tibial shaft tended to be slower in ORX rats compared with SHAM controls, the reduction in total cross-sectional area in ORX animals reached statistical significance only at 4 mo after surgery. The major mechanism for cortical bone loss in aged ORX rats was a progressive expansion of the marrow cavity, which was associated with an initial increase in endocortical eroded perimeter at 1 and 2 mo after surgery, followed by a sustained increase in endocortical bone formation until the end of the study. All these changes were prevented in aged ORX rats receiving testosterone supplementation in an insulin-like growth factor system–independent fashion.
Conclusions: We conclude that androgen deficiency–induced cortical bone loss in aged, nongrowing rats is mainly caused by augmented endocortical bone remodeling.
Interleukin-4 and Interleukin-13 Stimulate the Osteoclast Inhibitor Osteoprotegerin by Human Endothelial Cells Through the STAT6 Pathway
Authors: Stein Nicola C , Kreutzmann Carmen , Zimmermann Sara-Pia , Niebergall Ute , Hellmeyer Lars , Goettsch Claudia , Schoppet Michael , Hofbauer Lorenz C 
Published: February 2008

Abstract
Introduction: Endothelial cells of the bone vasculature modulate development, remodeling, and repair of bone by secreting osteotropic cytokines and hormones, which can act on osteoblastic and osteoclastic lineage cells. RANKL is the essential factor for differentiation, activation, and survival of osteoclasts, whereas osteoprotegerin (OPG) is a soluble decoy receptor and inhibitor for RANKL.
Materials and Methods: In this study, we analyzed the regulation of OPG by T helper 2 (Th2) cytokines interleukin (IL)-4 and the closely related IL-13 in human umbilical vein endothelial cells (HUVECs), the underlying signaling pathway, and its functional relevance on osteoclastic resorption.
Results: IL-4 and IL-13 induced OPG mRNA levels and protein secretion in HUVEC by up to 4-fold in a dose- and time-dependent fashion (maximum effect after 48 h and at 10 ng/ml). Activation of the transcription factor STAT6 preceded IL-4–induced OPG expression, and blockade of IL-4–induced STAT6 activation by the phospholipase C–specific inhibitor D609 decreased OPG expression. Soluble IL-4 receptor (sIL-4R) dose-dependently abolished both IL-4–induced STAT6 phosphorylation and OPG expression. RANKL stimulated the activity of osteoclasts, which was antagonized by HUVEC-derived supernatant containing OPG. The inhibitory effect on osteoclastogenesis was completely and specifically abrogated by a neutralizing OPG antibody in unstimulated HUVEC supernatant and partially in IL-4–stimulated HUVEC supernatant.
Conclusions: In summary, IL-4 and IL-13 induced OPG expression through activation of STAT6 in endothelial cells, and HUVEC-derived OPG is an IL-4/IL-13–induced inhibitor of osteoclastic resorption. These data underline the impact of Th2 cytokines on bone resorption through modulation of endothelial cell–derived cytokines.
Frequency and Risk Factors Associated With Osteonecrosis of the Jaw in Cancer Patients Treated With Intravenous Bisphosphonates
Authors: Hoff Ana O , Toth Béla B , Altundag Kadri , Johnson Marcella M , Warneke Carla L , Hu Mimi , Nooka Ajay , Sayegh Gilbert , Guarneri Valentina , Desrouleaux Kimberly , Cui Jeffrey , Adamus Andrea , Gagel Robert F , Hortobagyi Gabriel N 
Published: February 2008

Abstract
Introduction: Osteonecrosis of the jaw (ONJ) has been reported in patients treated with bisphosphonates. The incidence and risk factors associated with this disorder have not been clearly defined.
Materials and Methods: We conducted a retrospective analysis of 4019 patients treated with intravenous bisphosphonates between 1996 and 2004. Our goals were to estimate the frequency, understand the clinical presentation, and identify risk factors associated with ONJ development.
Results: Sixteen of 1338 patients with breast cancer (1.2%) and 13 of 548 patients with multiple myeloma (2.4%) developed ONJ. The median dose and duration of treatment with pamidronate or zoledronic acid were significantly higher in patients with ONJ (p &lt; 0.0001). Multivariate Cox proportional hazards regression analysis identified treatment with zoledronic acid (hazards ratio [HR], 15.01; 95% CI: 2.41–93.48; p = 0.0037), treatment with pamidronate followed by zoledronic acid (HR, 4.00; 95% CI: 0.86–18.70; p = 0.078), and dental extractions (HR, 53.19; 95% CI: 18.20–155.46; p &lt; 0.0001) as significant risks for ONJ in breast cancer. In multiple myeloma, dental extractions (HR, 9.78; 95% CI: 3.07–31.14; p = 0.0001) and osteoporosis (HR, 6.11; 95% CI: 1.56–23.98; p = 0.0095) were significant risk factors while controlling for bisphosphonate therapy. Thirteen of 29 patients were followed for a median of 17.1 mo (range, 7–67 mo); lesions healed in 3 patients during this period.
Conclusions: ONJ is an uncommon but long-lasting disorder that occurs mainly in breast cancer and multiple myeloma patients treated with intravenous bisphosphonates. High cumulative doses of bisphosphonates, poor oral health, and dental extractions may be significant risk factors for ONJ development. ONJ resolved in 23% of patients with conservative therapy.
Apoptotic Bodies Convey Activity Capable of Initiating Osteoclastogenesis and Localized Bone Destruction
Authors: Kogianni Giolanta , Mann Val , Noble Brendon S 
Published: February 2008

Abstract
Introduction: Osteocyte apoptosis co-localizes with sites of osteoclastic bone resorption in vivo, but to date, no causal molecular or signaling link has been identified between these two processes.
Materials and Methods: Osteocyte apoptotic bodies (OABs) derived from the MLO-Y4 osteocyte-like cell line and primary murine osteocytes and apoptotic bodies (ABs) derived from primary murine osteoblasts were introduced onto the right parietal bone of murine calvariae, and osteoclastic bone resorption was examined 5 days after treatment. In addition, the ability of primary murine and cell line–derived OABs to support osteoclastogenesis was examined in vitro in co-culture with murine bone marrow hematopoietic progenitors in the absence of RANKL or macrophage-colony stimulating factor.
Results: For the first time, we show that OABs are capable of initiating de novo osteoclastic bone resorption on quiescent bone surfaces in vivo. Furthermore, the addition of OABs to mononuclear osteoclast precursors (OPs) in vitro resulted in the maintenance of OP cell numbers and an increase in the proportion and activity of TRACP+ cells. In contrast, application of ABs from osteoblasts showed no osteoclastogenic activity either in vivo or in vitro. The osteoclastogenic capacity of OABs was shown to be independent of the known osteoclastogenic factor RANKL but dependent on the induction of TNF-α production by OP.
Conclusions: These data point to a mechanism by which dying osteocytes might target bone destruction through the distribution of OAB-associated signals and give further physiological meaning to the apoptotic process in bone.
Identification of Quantitative Trait Loci Affecting Murine Long Bone Length in a Two-Generation Intercross of LG/J and SM/J Mice
Authors: Norgard Elizabeth A , Roseman Charles C , Fawcett Gloria L , Pavličev Mihaela , Morgan Clinton D , Pletscher L Susan , Wang Bing , Cheverud James M 
Published: February 2008

Abstract
Introduction: Study of mutations with large phenotypic effects has allowed the identification of key players in skeletal development. However, the molecular nature of variation in large, phenotypically normal populations tends to be characterized by smaller phenotypic effects that remain undefined.
Materials and Methods: We use interval mapping and quantitative trait locus (QTL) mapping techniques in the combined F2-F3 populations (n = 2111) of an LG/J × SM/J mouse intercross to detect QTLs associated with the lengths of the humerus, ulna, femur, and tibia.
Results: Seventy individual trait QTLs affecting long bone lengths were detected, with several chromosomes harboring multiple QTLs. The genetic architecture suggests mainly small, additive effects on long bone length, with roughly one third of the QTLs displaying dominance. Sex interactions were common, and four sex-specific QTLs were observed. Pleiotropy could not be rejected for most of the QTLs identified. Thirty-one epistatic interactions were detected, almost all affecting regions including or immediately adjacent to QTLs.
Conclusions: A complex regulatory network with many gene interactions modulates bone growth, possibly with integrated skeletal modules that allow fine-tuning of developmental processes present. Candidate genes in the QTL CIs include many genes known to affect endochondral bone growth and genes that have not yet been associated with bone growth or body size but have a strong potential to influence these traits.