bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of a Polymorphism in the TNFR2 Gene with Low Bone Mineral Density
Authors: Spotila L. D. , Rodriguez H. , Koch M. , Adams K. , Caminis J. , Tenenhouse H. S. , Tenenhouse A.
Published: April 2006

Previous genetic linkage data suggested that a gene on chromosome 1p36.2–36.3 might be linked to low bone mineral density (BMD). Here, we examine the gene for tumor necrosis factor receptor 2 (TNFR2), a candidate gene within that interval, for association with low BMD in a group of 159 unrelated individuals. We assess two polymorphic sites within the gene, a microsatellite repeat within intron 4, and a three-nucleotide variation in the 3′ untranslated region (UTR) of the gene. The latter has five alleles of which the rarest allele is associated with low spinal BMD Z score (p = 0.008). Lowest mean spinal BMD Z scores were observed for individuals having genotypes that were heterozygous for the rarest allele. No homozygotes for the rarest allele were observed. Preliminary analysis suggests that there is a difference in the genotype frequency distribution between the group with low BMD and a control group.
Effect of Long-Term Exposure to Fluoride in Drinking Water on Risks of Bone Fractures
Authors: Li Yiming , Liang Chaoke , Slemenda Charles W. , Ji Rongdi , Sun Shuzhuang , Cao Jingxiang , Emsley Christine L. , Ma Feng , Wu Yunpeng , Ying Po , Zhang Yan , Gao Sujuan , Zhang Wu , Katz Barry P. , Niu Shiru , Cao Shouren , Johnston Conrad C.
Published: April 2006

Findings on the risk of bone fractures associated with long-term fluoride exposure from drinking water have been contradictory. The purpose of this study was to determine the prevalence of bone fracture, including hip fracture, in six Chinese populations with water fluoride concentrations ranging from 0.25 to 7.97 parts per million (ppm). A total of 8266 male and female subjects ≥50 years of age were enrolled. Parameters evaluated included fluoride exposure, prevalence of bone fractures, demographics, medical history, physical activity, cigarette smoking, and alcohol consumption. The results confirmed that drinking water was the only major source of fluoride exposure in the study populations. A U-shaped pattern was detected for the relationship between the prevalence of bone fracture and water fluoride level. The prevalence of overall bone fracture was lowest in the population of 1.00-1.06 ppm fluoride in drinking water, which was significantly lower (p < 0.05) than that of the groups exposed to water fluoride levels ≥4.32 and ≤0.34 ppm. The prevalence of hip fractures was highest in the group with the highest water fluoride (4.32-7.97 ppm). The value is significantly higher than the population with 1.00-1.06 ppm water fluoride, which had the lowest prevalence rate. It is concluded that long-term fluoride exposure from drinking water containing ≥4.32 ppm increases the risk of overall fractures as well as hip fractures. Water fluoride levels at 1.00-1.06 ppm decrease the risk of overall fractures relative to negligible fluoride in water; however, there does not appear to be similar protective benefits for the risk of hip fractures.
Microarray Analysis of Bone Morphogenetic Protein, Transforming Growth Factor β, and Activin Early Response Genes During Osteoblastic Cell Differentiation
Authors: De Jong Diana S. , Van Zoelen Everardus J. J. , Bauerschmidt Susanne , Olijve Wiebe , Steegenga Wilma T.
Published: April 2006

Bone morphogenetic protein (BMP) 2, a member of the transforming growth factor (TGF) β family, is a potent regulator of osteoblast differentiation. In addition, both TGF-β and activin A can either induce bone formation or inhibit bone formation depending on cell type and differentiation status. Although much is known about the receptors and intracellular second messengers involved in the action of TGF-β family members, little is known about how selectivity in the biological response of individual family members is controlled. In this study, we have investigated selective gene induction by BMP-2, TGF-β1 and activin A in relation to their ability to control differentiation of mouse mesenchymal precursor cells C2C12 into osteoblastic cells. TGF-β1 can inhibit BMP-2-induced differentiation of these cells, whereas activin A was found to be without morphogenetic effect. Using a gene expression microarray approach covering 8636 sequences, we have identified a total of 57 established genes and expressed sequence tags (ESTs) that were either up-regulated or down-regulated 2 h after treatment with at least one of these three stimuli. With respect to the established genes, 15 new target genes for TGF-β family members thus were identified. Furthermore, a set of transcripts was identified, which was oppositely regulated by TGF-β1 and BMP-2. Based on the inverse biological effects of TGF-β1 and BMP-2 on C2C12 cells, these genes are important candidates for controlling the process of growth factor-induced osteoblast differentiation.
Reversal of Secondary Hyperparathyroidism by Phosphate Restriction Restores Parathyroid Calcium-Sensing Receptor Expression and Function
Authors: Ritter Cynthia S. , Martin Daniel R. , Lu Yan , Slatopolsky Eduardo , Brown Alex J.
Published: April 2006

Secondary hyperparathyroidism (2° HPT), a common disorder in chronic renal failure (CRF) patients, is characterized by hypersecretion of parathyroid hormone (PTH), parathyroid hyperplasia, and decreased expression of the calcium-sensing receptor (CaR). Dietary phosphate loading promotes 2° HPT, and phosphate restriction prevents and arrests 2° HPT in CRF. This study examined the ability of phosphate restriction to restore parathyroid CaR expression and function. Uremic rats fed a 1.2% P diet for 2 weeks developed 2° HPT with down-regulated CaR expression. Continuation on the 1.2% P diet for 2 more weeks worsened the 2° HPT and further decreased CaR, but switching the rats to a 0.2% P diet for 2 weeks normalized PTH, arrested parathyroid hyperplasia, and restored CaR expression to normal. The calcium-PTH relationship was abnormal in uremic rats fed a high phosphate (HP) diet with a right-shifted calcium set point but was corrected by 2 weeks of phosphate restriction. A time course revealed that following the switch to a low phosphate diet, PTH levels were normalized by day 1, and growth was arrested by day 2, but CaR expression was restored between days 7 and 14. We conclude that although phosphate restriction restores CaR expression and function in parathyroid glands of uremic rats, it is a late event and not involved in the arrest of 2° HPT.
Ca2+ Signaling Mediated by IP3-Dependent Ca2+ Releasing and Store-Operated Ca2+ Channels in Rat Odontoblasts
Authors: Shibukawa Yoshiyuki , Suzuki Takashi
Published: April 2006

In the phospholipase-C (PLC) signaling system, Ca2+ is mobilized from intracellular Ca2+ stores by an action of inositol 1,4,5-trisphosphate (IP3). The depletion of IP3-sensitive Ca2+ stores activates a store-operated Ca2+ entry (SOCE). However, no direct evidence has been obtained about these signaling pathways in odontoblasts. In this study, we investigate the characteristics of the SOCE and IP3-mediated Ca2+ mobilizations in rat odontoblasts using fura-2 microfluorometry and a nystatin-perforated patch-clamp technique. In the absence of extracellular Ca2+ ([Ca2+]o), thapsigargin (TG) evoked a transient rise in intracellular Ca2+ concentration ([Ca2+]i). After TG treatment to deplete the store, the subsequent application of Ca2+ resulted in a rapid rise in [Ca2+]i caused by SOCE. In the absence of TG treatment, no SOCE was evoked. The Ca2+ influx was dependent on [Ca2+]o (KD = 1.29 mM) and was blocked by an IP3 receptor inhibitor, 2-aminoethoxydiphenyl borate (2-APB), as well as La3+ in a concentration-dependent manner (IC50 = 26 μM). In TG-treated cells, an elevation of [Ca2+]o from 0 to 2.5 mM elicited an inwardly rectifying current at hyperpolarizing potentials with a positive reversal potential. The currents were selective for Ca2+ over the other divalent cations (Ca2+ > Ba2+ > Sr2+ ≫ Mn2+). In the absence of [Ca2+]o, carbachol, bradykinin, and 2-methylthioadenosine 5′triphosphate activated Ca2+ release from the store; these were inhibited by 2-APB. These results indicate that odontoblasts possessed Ca2+ signaling pathways through the activation of store-operated Ca2+ channels by the depletion of intracellular Ca2+ stores and through the IP3-induced Ca2+ release activated by PLC-coupled receptors.
Calcyclin Mediates Serum Response Element (SRE) Activation by an Osteoblastic Extracellular Cation-Sensing Mechanism
Authors: TU Qisheng , PI Min , Quarles L Darryl
Published: April 2006

The molecular mechanism of sensing extracellular cations in osteoblasts is controversial. Using an expression-cloning strategy, the calcium-binding protein calcyclin was found to mediate the response of MC3T3-E1 osteoblasts to extracellular cations, but not the calcimimetic NPS-568, indicating the presence of another cation-sensing mechanism. Further understanding of calcyclin function in osteoblasts may identify novel targets for regulating bone formation.

Introduction: Extracellular calcium and other cations seem to regulate the function of osteoblasts through a distinct calcium-sensing mechanism that is coupled to activation of c-fos gene transcription. The identity of this calcium-sensing mechanism is unknown.

Methods: To identify molecules that participate in this extracellular cation-sensing pathway, we developed an expression cloning strategy in COS-7 cells using cation stimulation of a serum response element (SRE) luciferase reporter derived from the c-fos promoter to screen a mouse MC3T3-E1 osteoblast cDNA library.

Results and Conclusions: We identified calcyclin (S100A6), a calcium-binding protein of the EF-hand type belonging to the S100 family, as being responsible for transferring a cation-sensing response from osteoblasts to COS-7 cells. Transfection of the calcyclin cDNA into COS-7 and HEK-293 cells confirmed that the overexpression of calcylin caused these cells to gain the ability to sense extracellular cations, including aluminum, gadolinium, calcium, and magnesium. Conversely, we found that an antisense calcyclin construct reduced calcyclin expression and partially inhibited the cation-sensing response in MC3T3-E1 osteoblasts. These results implicate calcyclin in the activation of SRE and establish a role for calcyclin as an accessory protein involved in the cation-sensing pathway in osteoblasts.
Functional Differences Between Growth Plate Apoptotic Bodies and Matrix Vesicles
Authors: Kirsch Thorsten , Wang Wei , Pfander David
Published: April 2006

Mineralization often occurs in areas of apoptotic changes. Our findings indicate that physiological mineralization is mediated by matrix vesicles. These matrix vesicles use mechanisms to induce mineralization that are different from the mechanisms used by apoptotic bodies released from apoptotic cells. Therefore, different therapeutic approaches must be chosen to inhibit pathological mineralization depending on the mechanism of mineralization (matrix vesicles versus apoptotic bodies).

Introduction: Physiological mineralization in growth plate cartilage is restricted to regions of terminally differentiated and apoptotic chondrocytes. Pathological mineralization of tissues also often occurs in areas of apoptosis. We addressed the question of whether apoptotic changes control mineralization events or whether both events are regulated independently.

Methods: To induce mineralization, we treated growth plate chondrocytes with retinoic acid (RA); apoptosis in these cells was induced by treatment with staurosporine, anti-Fas, or TNFα. The degrees of mineralization and apoptosis were determined, and the structure and function of matrix vesicles and apoptotic bodies were compared.

Results: Release of matrix vesicles and mineralization in vivo in the growth plate occurs earlier than do apoptotic changes. To determine the functional relationship between apoptotic bodies and matrix vesicles, growth plate chondrocytes were treated with RA to induce matrix vesicle release and with staurosporine to induce release of apoptotic bodies. After 3 days, approximately 90% of staurosporine-treated chondrocytes were apoptotic, whereas only 2–4 % of RA-treated cells showed apoptotic changes. RA- and staurosporine-treated chondrocyte cultures were mineralized after 3 days. Matrix vesicles isolated from RA-treated cultures and apoptotic bodies isolated from staurosporine-treated cultures were associated with calcium and phosphate. However, matrix vesicles were bigger than apoptotic bodies. Furthermore, matrix vesicles but not apoptotic bodies contained alkaline phosphatase and Ca2+ channel-forming annexins II, V, and VI. Consequently, matrix vesicles but not apoptotic bodies were able to take up Ca2+ and form the first mineral phase inside their lumen. Mineralization of RA-treated cultures was inhibited by antibodies specific for annexin V but not mineralization of staurosporine-treated cultures.

Conclusion: Physiological mineralization of growth plate chondrocytes is initiated by specialized matrix vesicles and requires alkaline phosphatase and annexins. In contrast, mineral formation mediated by apoptotic bodies occurs by a default mechanism and does not require alkaline phosphatase and annexins.
Estrogen and Bone—a Reproductive and Locomotive Perspective
Authors: Järvinen Teppo Ln , Kannus Pekka , Sievänen Harri
Published: April 2006

The primary function of the skeleton is locomotion, and the primary function of estrogen is reproduction. When the skeleton is considered within this locomotive context, the onset of estrogen secretion at puberty leads to packing of mechanically excess mineral into female bones for reproductive needs. Accordingly, the unpacking of this reproductive safety deposit at menopause denotes the origin of type I osteoporosis.

Introduction: According to the prevailing unitary model of involutional osteoporosis, female postmenopausal bone loss can be described as having an initial accelerated, transient phase (type I), followed by a gradual continuous phase (type II). Estrogen withdrawal is generally accepted as the primary cause of the type I osteoporosis. Thus, the quest to uncover the origin of type I osteoporosis has focused on the estrogen withdrawal-related skeletal changes at and around the menopause. However, considering that the cyclical secretion of estrogen normally begins in early adolescence and continues over the entire fertile period, one could argue that focusing on perimenopause alone may be too narrow.

Materials and Methods: This is not a systematic review of the literature on the skeletal function of estrogen(s), but rather, an introduction of a novel structure- and locomotion-oriented perspective to this particular issue through pertinent experimental and clinical studies.

Results and Conclusions: When considering locomotion as the primary function of the skeleton and integrating the classic findings of the pubertal effects of estrogen on female bones and the more recent hypothesis-driven experimental and clinical studies on estrogen and mechanical loading on bone within this context, a novel evolution-based explanation for the role of estrogen in controlling female bone mass can be outlined: the onset of estrogen secretion at puberty induces packing of mechanically excess bone into female skeleton for needs of reproduction (pregnancy and lactation). Accordingly, the unpacking of this reproductive safety deposit of calcium at menopause denotes the accelerated phase of bone loss and thus the origin of type I osteoporosis.
Recombinant Human Parathyroid Hormone (1–34) [Teriparatide] Improves Both Cortical and Cancellous Bone Structure
Authors: Jiang Yebin , Zhao Jenny J , Mitlak Bruce H , Wang Ouhong , Genant Harry K , Eriksen Erik F
Published: April 2006

Histomorphometry and μCT of 51 paired iliac crest biopsy specimens from women treated with teriparatide revealed significant increases in cancellous bone volume, cancellous bone connectivity density, cancellous bone plate-like structure, and cortical thickness, and a reduction in marrow star volume.

Introduction: We studied the ability of teriparatide (rDNA origin) injection [rhPTH(1–34), TPTD] to improve both cancellous and cortical bone in a subset of women enrolled in the Fracture Prevention Trial of postmenopausal women with osteoporosis after a mean treatment time of 19 months. This is the first report of a biopsy study after treatment with teriparatide having a sufficient number of paired biopsy samples to provide quantitative structural data.

Methods: Fifty-one paired iliac crest bone biopsy specimens (placebo [n = 19], 20 μg teriparatide [n = 18], and 40 μg teriparatide [n = 14]) were analyzed using both two-dimensional (2D) histomorphometry and three-dimensional (3D) microcomputed tomography (μCT). Data for both teriparatide treatment groups were pooled for analysis.

Results and Conclusions: By 2D histomorphometric analyses, teriparatide significantly increased cancellous bone volume (median percent change: teriparatide, 14%; placebo, −24%; p = 0.001) and reduced marrow star volume (teriparatide, −16%; placebo, 112%; p = 0.004). Teriparatide administration was not associated with osteomalacia or woven bone, and there were no significant changes in mineral appositional rate or wall thickness. By 3D cancellous and cortical bone structural analyses, teriparatide significantly decreased the cancellous structure model index (teriparatide, −12%; placebo, 7%; p = 0.025), increased cancellous connectivity density (teriparatide, 19%; placebo, −14%; p = 0.034), and increased cortical thickness (teriparatide, 22%; placebo, 3%; p = 0.012). These data show that teriparatide treatment of postmenopausal women with osteoporosis significantly increased cancellous bone volume and connectivity, improved trabecular morphology with a shift toward a more plate-like structure, and increased cortical bone thickness. These changes in cancellous and cortical bone morphology should improve biomechanical competence and are consistent with the substantially reduced incidences of vertebral and nonvertebral fractures during administration of teriparatide.
The ClC-5 Knockout Mouse Model of Dent's Disease Has Renal Hypercalciuria and Increased Bone Turnover
Authors: Silva Ian V , Cebotaru Valeriu , Wang Hua , Wang Xi-Tao , Wang Sha Sha , Guo Gang , Devuyst Olivier , Thakker Rajesh V , Guggino William B , Guggino Sandra E
Published: April 2006

Dent's disease is a nephrolithiasis disorder associated with hypercalciuria and low molecular weight proteinuria that is caused by mutations in the voltage-gated chloride channel ClC-5. Because the exact cause of hypercalciuria in this disease is unknown and could come from a renal, intestinal, or bone origin, we have investigated overall calcium handling in the ClC-5 knockout mouse (ClC-5 KO). On a high calcium diet, ClC-5 KO mice had elevated serum 1α,25-dihydroxyvitamin D3 (1α,25D3), alkaline phosphatase (AP), osteocalcin (OC), and urinary deoxypyridinoline (DPD), but serum parathyroid hormone (PTH), calcium, and intestinal calcium uptake was similar to that of wild-type (WT) mice. A 30-fold decrease in dietary calcium intake caused elevation of serum PTH and urinary cyclic adenosine monophosphate in ClC-5 KO mice and decreased the renal calcium excretion, which still remained 2-fold above that of WT mice. On this low calcium diet, both groups of mice had the same serum 1α,25D3, with similar increments in intestinal calcium absorption, serum AP, OC, and urinary DPD. These data indicate that the hypercalciuria in the ClC-5 KO mice on low and high calcium diets is of bone and renal origin and is not caused by increased intestinal calcium absorption, despite an elevated serum 1α,25D3. These mice data suggest that young patients with this disease may have a propensity for altered bone homeostasis that should be monitored clinically.
Renal Calcification in Mice Homozygous for the Disrupted Type IIa Na/Pi Cotransporter Gene Npt2
Authors: Chau Hien , El-Maadawy Sherif , McKEE Marc D , Tenenhouse Harriet S
Published: April 2006

Mice homozygous for the disrupted renal type IIa sodium/phosphate (Na/Pi) cotransporter gene (Npt2−/−) exhibit renal Pi wasting, hypophosphatemia, and an adaptive increase in the serum concentration of 1,25-dihydroxyvitamin D with associated hypercalcemia and hypercalciuria. Because hypercalciuria is a risk factor for nephrocalcinosis, we determined whether Npt2−/− mice form renal stones. Analysis of renal sections by von Kossa staining and intact kidneys by microcomputed tomography revealed renal calcification in adult Npt2−/− mice but not in Npt2+/+ littermates. Energy-dispersive spectroscopy and selected-area electron diffraction indicated that the calcifications are comprised of calcium and Pi with an apatitic mineral phase. To determine the age of onset of nephrocalcinosis, we examined renal sections of newborn and weanling mice. At both ages, mutant but not wild-type mice display renal calcification, which is associated with renal Pi wasting and hypercalciuria. Immunohistochemistry revealed that osteopontin co-localizes with the calcifications. Furthermore, renal osteopontin messenger RNA abundance is significantly elevated in Npt2−/− mice compared with Npt2+/+ mice. The onset of renal stones correlated developmentally with the absence of Npt2 expression and the expression of the genes responsible for the renal production (1α-hydroxylase) and catabolism (24-hydroxylase) of 1,25-dihydroxyvitamin D. In summary, we show that Npt2 gene ablation is associated with renal calcification and suggest that mutations in the NPT2 gene may contribute to nephrocalcinosis in a subset of patients with familial hypercalciuria.
Fibroblast Growth Factors Lead to Increased Msx2 Expression and Fusion in Calvarial Sutures
Authors: Ignelzi Michael A , Wang Wei , Young Andrew T
Published: April 2006

Craniosynostosis, the premature fusion of the skull bones at the sutures, represents a disruption to the coordinated growth and development of the expanding brain and calvarial vault and is the second most common birth defect that affects the craniofacial complex. Mutations in the human homeobox-containing gene, Msx2, have been shown to cause Boston type craniosynostosis, and we have shown that overexpression of Msx2 leads to craniosynostosis in mice. Activating mutations in fibroblast growth factor (FGF) receptors are thought to cause craniosynostosis in Crouzon, Apert, Jackson-Weiss, Beare-Stevenson, and Muenke syndromes. To mimic activated signaling by mutated FGF receptors, we used heparin acrylic beads to deliver FGF ligands to mouse calvaria and demonstrated increased Msx2, Runx2, Bsp, and Osteocalcin gene expression, decreased cell proliferation, and suture obliteration and fusion. FGF2 elicited the greatest increase in Msx2 expression, and FGF1 was most likely to cause suture obliteration and fusion. Of the three sutures studied, the coronal suture exhibited the greatest increase in Msx2 expression and was the most likely to undergo obliteration and fusion. These results are intriguing because the coronal suture is the most commonly affected suture in syndromic craniosynostosis. These results suggest that Msx2 is a downstream target of FGF receptor signaling and that increased FGF signaling leads to osteogenic differentiation by sutural mesenchyme in mouse calvaria. These results are consistent with the hypotheses that increased Msx2 expression and activated signaling by mutated FGF receptors lead to craniosynostosis.
Estrogen Receptor α Gene Polymorphisms and Peak Bone Density in Chinese Nuclear Families
Authors: Qin Yue-Juan , Shen Hui , Huang Qi-Ren , Zhao Lan-Juan , Zhou Qi , Li Miao-Xin , He Jin-Wei , Mo Xiao-Yang , Lu Jing-Hui , Recker Robert R , Deng Hong-Wen
Published: April 2006

PBD is an important determinant of osteoporotic fractures. Few studies were performed to search for genes underlying PBD variation in Chinese populations. We tested linkage and/or association of the estrogen receptor α gene polymorphism with PBD in 401 Chinese nuclear families. This study suggests the ER-α gene may have some minor effects on PBM variation in the Chinese population.

Low peak bone density (PBD) in adulthood is an important determinant of osteoporotic fractures in the elderly. PBD variation is mainly regulated by genetic factors. Extensive molecular genetics studies have been performed to search for genes underlying PBD variation, largely in whites. Few studies were performed in Chinese populations. In this study, we simultaneously test linkage and/or association of the estrogen receptor α (ER-α) gene polymorphism with PBD in 401 Chinese nuclear families (both parents plus their female children) of 1260 subjects, with the 458 children generally between 20 and 40 years of age. All the subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) at polymorphic PvuII and XbaI sites inside the ER-α gene. Bone mineral density was measured at the lumbar spine (L1-L4) and hip (femoral neck, trochanter, and intertrochanteric region). Raw bone mineral density values were adjusted by age, height, and weight as covariates. We detected marginally significant results for within-family association (transmission disequilibrium; p = 0.054) between the spine bone mineral density variation and the ER-α XbaI genotypes. For the hip bone mineral density variation, significant (p < 0.05) linkage results were generally found for the two intragenic markers. Analyses of the haplotypes defined by the two markers confer further evidence for linkage of the ER-α with the hip PBD variation. In conclusion, this study suggests that the ER-α gene may have minor effects on PBD variation in our Chinese population.
Effect of Hormone Replacement Therapy on Bone Quality in Early Postmenopausal Women
Authors: Paschalis Ep , Boskey Al , Kassem M , Eriksen Ef
Published: April 2006

HRT is an effective prophylaxis against postmenopausal bone loss. Infrared imaging of paired iliac crest biopsies obtained at baseline and after 2 years of HRT therapy demonstrate an effect on the mineral crystallinity and collagen cross-links that may affect bone quality.

Several studies have demonstrated that hormonal replacement therapy (HRT) is an effective prophylaxis against postmenopausal bone loss, although the underlying mechanisms are still debated. Infrared spectroscopy has been used previously for analyzing bone mineral crystallinity and three-dimensional structures of collagen and other proteins. In the present study, the technique of Fourier transform infrared microscopic imaging (FTIRI) was used to investigate the effect of estrogen on bone quality (arbitrarily defined as mineral/matrix ratio, mineral crystallinity/maturity, and relative ratio of collagen cross-links [pyridinoline/deH-DHLNL]) at the ultrastructural level, in mineralized, thin tissue sections from double (before and after administration of HRT regimen; cyclic estrogen and progestogen [norethisterone acetate]) iliac crest biopsy specimens from 10 healthy, early postmenopausal women who were not on any medication with known influence on calcium metabolism. FTIRI allows the analysis of undemineralized thin tissue sections (each image analyzes a 400 × 400 μm2 area with a spatial resolution of ∼6.3 mm). For each bone quality variable considered, the after-treatment data exhibited an increase in the mean value, signifying definite changes in bone properties at the molecular level after HRT treatment. Furthermore, these findings are consistent with suppressed osteoclastic activity.
Femoral Neck Response to Exercise and Subsequent Deconditioning in Young and Adult Rats
Authors: Järvinen Teppo LN , Pajamäki Ilari , Sievänen Harri , Vuohelainen Tuomo , Tuukkanen Juha , Järvinen Markku , Kannus Pekka
Published: April 2006

Aged bones have been considered to have reduced capacity to respond to changes in incident loading. By subjecting young and adult rats to increased loading and subsequent deconditioning, we observed quantitatively similar adaptive responses of bone in these two groups, but young skeletons adapted primarily through geometric changes and adult bones through increased volumetric density. Loss of the exercise-induced bone benefits did not depend on age.

Introduction: Aging has been shown to decrease the sensitivity of the mechanosensory cells of bones to loading-induced stimuli, presumably resulting in not only reduced capacity but also different adaptive mechanism of the aged skeleton to altered loading, as well as poorer capacity to preserve exercise-induced bone benefits.

Materials and Methods: Fifty young (5-week-old) and 50 adult (33-week-old) male rats were randomized into control and exercise (+deconditioning) groups. After a 14-week progressively intensified running program, one-half of the exercised rats (both young and adult) were killed, and the remaining rats underwent subsequent 14-week period of deconditioning (free cage activity). A comprehensive analysis of the femoral neck was performed using peripheral quantitative computed tomography and mechanical testing.

Results: In comparison with the controls, both young and adult exercised rats had significant increases in almost all measured parameters: +25% (p < 0.001) and +10% (not significant [NS]) in the cross-sectional area; +28% (p < 0.001) and +18% (p < 0.001) in bone mineral content; +11% (p < 0.05) and +23% (p < 0.001) in bone mineral density; and +30% (p < 0.01) and +28% (p < 0.01) in the breaking load, respectively. The skeletal responses were not statistically different between the young and adult rats. After the 14-week period of deconditioning, the corresponding exercised-to-controls differences were +17% (p < 0.05) and +10% (NS), +18% (p < 0.05) and +13% (p < 0.05), +2% (NS) and +2% (NS), and +11% (NS) and +6% (NS), respectively. Again, the response differences were not significant between the age groups.

Conclusion: Quantitatively, the capacity of the young and adult skeleton to adapt to increased loading was similar, but the adaptive mechanisms appeared different: growing bones seemed to primarily display geometric changes (increase in bone size), whereas the adult skeleton responded mainly through an increase in density. Despite this apparent difference in the adaptive mechanism, aging did not modulate the ability of the skeleton to preserve the exercise-induced bone gain, because the bone loss was similar in the young and adult rats after cessation of training.
Eosinophil Chemotactic Factor-L (ECF-L): A Novel Osteoclast Stimulating Factor
Authors: Oba Yasuo , Chung HO Yeon , Choi Sun Jin , Roodman G David
Published: April 2006

Screening a cDNA library enriched for genes expressed in OCLs identified ECF-L. ECF-L enhanced OCL formation without increasing RANKL levels. Anti-ECF-L inhibited RANKL-induced OCL formation. These results support a potent role of ECF-L in osteoclastogenesis.

Introduction: To investigate the molecular mechanisms that control osteoclastogenesis, we developed an immortalized osteoclast (OCL) precursor cell line that forms mature OCLs in the absence of stromal cells and used it to form pure populations of OCLs.

Materials and Methods: Polymerase chain reaction (PCR) selective cDNA subtraction was used to identify genes that are highly expressed in mature OCLs compared with OCL precursors employing OCL and OCL precursors derived from this cell line.

Results: Eosinophil chemotactic factor-L (ECF-L), a previously described chemotactic factor for eosinophils, was one of the genes identified. Conditioned media from 293 cells transfected with mECF-L cDNA, or purified ECF-L Fc protein, increased OCL formation in a dose-dependent manner in mouse bone marrow cultures treated with 10−10 M 1,25(OH)2D3. OCLs derived from marrow cultures treated with ECF-L conditioned media formed increased pit numbers and resorption area per dentin slice compared with OCLs induced by 1,25(OH)2D3 (p < 0.01). Addition of an antisense S-oligonucleotide to mECF-L inhibited OCL formation in murine bone marrow cultures treated only with 10−9 M 1,25(OH)2D3 compared with the sense S-oligonucleotide control. Time course studies demonstrated that ECF-L acted at the later stages of OCL formation, and chemotactic assays showed that mECF-L increased migration of OCL precursors. mECF-L mRNA was detectable in mononuclear and multinucleated cells by in situ hybridization. Interestingly, a neutralizing antibody to ECF-L blocked RANKL or 10−9 M 1,25(OH)2D3-induced OCL formation in mouse bone marrow cultures, although ECF-L did not induce RANKL expression.

Conclusions: These data show ECF-L is a previously unknown factor that is a potent mediator of OCL formation, which acts at the later stages of OCL formation and enhances the effects of RANKL.
Reelin Deficiency and Displacement of Mature Neurons, But Not Neurogenesis, Underlie the Formation of Granule Cell Dispersion in the Epileptic Hippocampus
Authors: Heinrich Christophe , Nitta Naoki , Flubacher Armin , Müller Martin , Fahrner Alexander , Kirsch Matthias , Freiman Thomas , Suzuki Fumio , Depaulis Antoine , Frotscher Michael , Haas Carola A.
Published: April 2006

Mesio-temporal lobe epilepsy (MTLE) is often accompanied by granule cell dispersion (GCD), a widening of the granule cell layer. The molecular determinants of GCD are poorly understood. Here, we used an animal model to study whether GCD results from an increased dentate neurogenesis associated with an abnormal migration of the newly generated granule cells. Adult mice were given intrahippocampal injections of kainate (KA) known to induce focal epileptic seizures and GCD, comparable to the changes observed in human MTLE. Ipsilateral GCD progressively developed after KA injection and was paralleled by a gradual decrease in the expression of doublecortin, a marker of newly generated granule cells, in the dentate subgranular layer. Staining with Fluoro-Jade B revealed little cell degeneration in the subgranular layer on the KA-injected side. Labeling with bromodeoxyuridine showed an early, transient increase in mitotic activity in the dentate gyrus of the KA-injected hippocampus that gave rise to microglial cells and astrocytes but not to new neurons. Moreover, at later time points, there was a virtually complete cessation of mitotic activity in the injected hippocampus (where GCD continued to develop), but not on the contralateral side (where no GCD was observed). Finally, a significant decrease in reelin mRNA synthesis in the injected hippocampus paralleled the development of GCD, and neutralization of reelin by application of the CR-50 antibody induced GCD. These results show that GCD does not result from increased neurogenesis but reflects a displacement of mature granule cells, most likely caused by a local reelin deficiency.
Miniaturized, Autoclavable Surgical Robot (Miniaturisierter, autoklavierbarer Roboter für die Chirurgie)
Authors: Koulechov Kirill , Rapoport Tobias , Lueth Tim C.
Published: April 2006

In this paper a design for a miniaturized, autoclavable robot for medicine is presented. The design is motivated by problems like size, visibility of the situs and the sterility of the operating field of known surgical robotics systems. The authors present a simple yet effective approach for closed loop control and a kinematics that addresses and solves these problems. Experiments show that properties like positioning precision and mechanical resistance during autoclaving are sufficient for certain clinical applications.
Rapid Control Prototyping petrinetzbasierter Steuerungen mit dem Tool NETLAB (Rapid Control Prototyping of Petri Net Based Controllers with the Tool NETLAB)
Authors: Orth Philipp , Abel Dirk
Published: April 2006

Der Beitrag beschreibt das Rapid Prototyping ereignisdiskreter Steuerungen. Während des Entwurfsprozesses wird mit dem Petrinetz-Zustandsraum-Modell (PNZRM) eine auf S/T-Netzen beruhende hybride Modellform genutzt. Mit Netlab steht ein Aufsatz für Matlab/Simulink zur Verfügung, der die Beschreibung ausführbarer ereignisdiskreter Modelle unterstützt und so innerhalb der Entwurfsumgebung die Modellierung in der Form des PNZRM ermöglicht. Netlab bietet auch eine zum Real-Time Workshop kompatible C-Code-Generierung. Der stark auf die grafische Darstellung ausgerichtete Ansatz ist vielversprechend in Bezug auf die Selbstdokumentation der erstellten Modelle. Zudem eröffnen die Programmier-Schnittstellen von Netlab neue Möglichkeiten bei der Erforschung und praktischen Erprobung von Entwurfsmethoden.
Incensed: Food Smells and Ethnic Tension
Authors: wurgaft benjamin aldes
Published: April 2006

Smell, often characterized as our least evolved or most "base" sense, is often invoked in ethnocentrist and racist discourse intended to create barriers between groups. The offensive smells of a given group's foods are often cited as a reason why they must be kept out of a pre-existing community. This essay argues that the reasons for this phenomenon are rooted in our anxiety about smell itself: it represents a pathway through which the particles of food literally penetrate us: a point of vulnerability. By examining a range of cases, from that of the medieval "Jewish odor" to the modern smells of Indian cooking in middle American kitchens, this essay explores the persistent connection between food smells and inter-ethnic tension.
The Truth In Thai Wine
Authors: pigott stuart
Published: April 2006

A widely-held theory amongst wine professionals says that premium quality winegrowing is impossible closer to the equator than 30°° latitude North and South. However, since 1995 a small group of Thai entrepreneurs and Thai winemakers have proved that impressive reds can be produced from the Syrah/Shiraz grape and dry whites from Chenin Blanc between 12°° and 18°° North in regions with a monsoon climate. Tropical viticulture requires a completely different approach to winegrowing in regions with temperate and Mediterranean climates. The mastering of this technique in Thailand, India and Tanzania during recent years opens a new era in global winegrowing. More radical still are the premium quality wines being produced in Thailand from local fruits, herbs, hone and even roots. Stuart Pigott takes the reader with him on a roller-coaster journey through the genuinely "new world" of tropical winegrowing and winemaking.
The Political Production of a Language
Authors: Crowley Tony
Published: April 2006

The assertion that a language is a dialect with an army and a navydraws attention to the fact that the distinction between the two is more likely to be based on political imperatives rather than linguistic features. The aim of this article is to examine a specific example of a form of language, Ulster‐Scots, whose status varies between dialect and language. It will be argued that in the context of contemporary Northern Ireland, the distinction has serious political consequences in relation to identity, rights, and the possibilities for a settlement to a deep and extended conflict.
The Road Signs of Reading
Authors: Welker William A.
Published: April 2006

The classroom strategy described in this article demonstrates to students the importance of “limiting words” in context. The many signal words in reading that affect the meaning of sentences can be classified as positive or negative. The author begins by sharing his unfortunate limiting‐word experience with the students as an introduction to “road‐sign words.” This approach activates students' prior experiences, which they share with their classmates. Then the author introduces the students to road‐sign words by using direct instruction methods. The students are exposed to limiting‐word examples in the content areas, in various classroom texts, and in their daily lives. Student activities include teacher‐student discussion, student development of road‐sign‐word sentences in class, and a homework assignment in which they are instructed to find examples of road‐sign words from various outside sources. Finally, the students are tested on their understanding of “signal words” via teacher‐constructed evaluations.
Genotypic Variability in Morphological and Physiological Traits among Maize Inbred Lines—Nitrogen Responses
Authors: D'Andrea K. E. , Otegui M. E. , Cirilo A. G. , Eyhérabide G.
Published: April 2006

A better understanding of the physiological processes related to nitrogen (N) metabolism in maize (Zea mays L.) inbred lines is important for increasing the efficiency of breeding programs targeting low‐N environments. This study analyzed the response to contrasting N availability of morphophysiological traits in a set of 12 maize inbred lines, from different origins (USA and Argentina) and breeding eras (from 1952 onward). Traits included in the analysis were related to canopy structure, light interception, shoot biomass production, and grain yield. Our results indicate that (i) the start of N effects on canopy size was more related to a threshold crop leaf area index (about 2) than to a given leaf stage (i.e., Vn), (ii) the light attenuation coefficient value was not affected by N availability, (iii) variations in kernel number per plant were explained by prolificacy (r2 = 0.59), and (iv) differences in harvest index were related to kernel number per plant (r2 = 0.77). The most important finding of our research was the detection in some inbreds of a particular response of kernel number to plant growth rate around silking, different from the general model established for hybrids. In these inbreds an additional effect of N availability was detected as reduced kernel set at a given plant growth rate under N deficient conditions (i.e., reduced reproductive efficiency). This result highlights the need of more research on reproductive sink development in this type of germplasm.
Litter Mass, Deposition Rate, and Chemical Composition in Bahiagrass Pastures Managed at Different Intensities
Authors: Dubeux J. C. B. , Sollenberger L. E. , Vendramini J. M. B. , Stewart R. L. , Interrante S. M.
Published: April 2006

Plant litter is an important pathway of nutrient return to the soil in grazed swards, but the effects of pasture management on litter mass and composition are not well understood. This research evaluated the effect of management intensity, defined in terms of N fertilization and stocking rate (SR), on litter mass, deposition rate, and chemical composition in continuously stocked ‘Pensacola’ bahiagrass (Paspalum notatum Flügge) pastures growing on Pomona and Smyrna sands. Treatments were three management intensities: Low (40 kg N ha−1 yr−1 and 1.3 animal units [AU, one AU = 500 kg live weight] ha−1 SR), Moderate (120 kg N ha−1 yr−1 and 2.7 AU ha−1 SR), and High (360 kg N ha−1 yr−1 and 4.0 AU ha−1 SR). Greater management intensity resulted in less litter mass on the pasture early in the growing season and more litter mass later in the season. Rate of litter deposition was generally greatest for High and ranged between 23 and 40 kg organic matter (OM) ha−1 d−1 compared with 13 to 30 kg OM ha−1 d−1 for Low and Moderate management intensities. Increasing management intensity from Low to High resulted in greater litter N (14.1 vs. 22.9 g kg−1) and P (0.8 vs. 1.3 g kg−1) concentrations and lesser C:N (∼40 vs. 22), C:P (649 vs. 433), and lignin:N (5.8 vs. 4.4) ratios. More intensive pasture management was associated with greater litter deposition rate and litter quality than less intensive management, suggesting a larger nutrient contribution from litter in intensively managed swards.
British Neo-naturalism
Authors: Trussler Simon
Published: April 2006

Naturalism wasn't a label any of the early new-wave British dramatists would have chosen deliberately, but a shape for which they reached instinctively: it happened to meet many of the demands which they were beginning to make on the English theatre. It served as a convenient vehicle for direct social comment, as opposed—very much opposed—to that poeticism in symbolic drawing-rooms which delighted the cultural establishment, and which was being vaunted abroad by the British Council as a renaissance of verse drama. Eliot's high toryism was as much out-of-tune politically with the new dramatists as his sugar-coated cadences were stylistically ill-adapted to their themes. Conversely, naturalism was a time-honored form for the problem play, and well suited to the semi-autobiographical idiom in which the new-wavers tended to play with their problems.
Pinter and Chekhov: The Bond of Naturalism
Authors: Lahr John
Published: April 2006

We begin with the idea that nature is all we need; it is necessary to accept her as she is, without modifying her or diminishing her in any respect; she is sufficiently beautiful and great to provide a beginning, a middle, and an end. Instead of imagining an adventure, complicating it, and arranging a series of theatrical effects to lead to a final conclusion, we simply take from life the story of a being or a group of beings whose acts we faithfully set down. The work becomes an official record, nothing more; its only merit is that of exact observation, of the more or less profound penetration of analysis, of the logical concatenation of facts …

“On Naturalism in the Theatre,” Emile Zola (1880)

Naturalism has its roots in a scientific approach which melds man inextricably to his environment, studying him as a complex amalgam of audible rhythms and spectacular mutations for survival. Chekhov, the passionate doctor, applied this discipline to the ailing conventional drama of his time.
Eugenio Barba's Kaspariana
Authors: Fumaroli Marc
Published: April 2006

Holstebro is a Danish town which nourishes ambitions rather like those of an Italian Renaissance city-state, where the rise of bourgeois economics was accompanied by dreams of artistic splendor. The Scandinavian Welfare State seems uneasy; there is a kind of neurotic squeak in the well-oiled machinery of daily life. An ultramodern industrial center, Holstebro—perhaps as unconscious compensation for its wealth—now hopes to become a center for “culture.” The city fathers of this small provincial town have built one of the two largest stages in Denmark, “bought” a young composer of electronic music and commissioned him to create a laboratory of musical research; they subsidize a good amateur orchestra and plan to install a professional one; finally, they have given Eugenio Barba the means of creating a theatre lab on the model of Jerzy Grotowski's at Wrøclaw—Odin Teatret (Nordisk Teaterlaboratorium for Skuespillerkunst).
Mutual Creation
Authors: Halprin Ann
Published: April 2006

“Myths” are experimental. The performers, members of the Dancers’ Workshop Co. and participants in Ann Halprin's Advanced Dance seminar, are unrehearsed. What unfolds is a spontaneous exploration of theatre ideas. “Myths” are meant to evoke our long buried and half forgotten selves. Each evening will explore a different relationship between the audience and performers, and between our awareness, our bodies, and our environments. The audience should not be bound by accustomed passivity, by static self images, or by restricted clothing. “Myths” are your myths. They are an experiment in mutual creation.

For 10 consecutive Thursdays, starting in October 1967, groups of about 50 people came to the Dancers’ Workshop studios in San Francisco. Most of them expected a “performance,” and instead found themselves “performers.” The Workshop had attempted to prepare the public by mailing the above announcement, but people were too pre-conditioned to understand what the release meant, and could only be convinced by the actual experience.
Experimental Performance at the Edinburgh Festival
Authors: Calandra Denis
Published: April 2006

Edinburgh is an impressive place to hold a festival: its center, where virtually all of the activities take place, is dominated by a sixteenth-century castle perched at the top of a steep craggy rock. From there the “Royal Mile,” consisting of a main artery, myriad picturesque alleys, and tall grey sandstone buildings, stretches to Holyrock Palace, the domicile of former Scottish kings. “Auld Reekie,” as this area is called, has a brooding quality to it, somewhat like the old city of Prague: One feels it should always be raining. The hilly geography extends to the southeast, where the legendary “Arthur's Seat,” described as a “volcanic eminence,” overlooks Holyrock Park and the rest of the city.