bluuebunny/crossref_metadata_2025 huggingface dataset:
Melatonin at Pharmacologic Doses Increases Bone Mass by Suppressing Resorption Through Down-Regulation of the RANKL-Mediated Osteoclast Formation and Activation
Authors: Koyama Hiroki , Nakade Osamu , Takada Yukihiro , Kaku Tohru , Lau K.-H. William
Published: April 2006

This study evaluated if melatonin would increase bone mass in mice. Four groups of 4-week-old male ddy mice received daily injections of vehicle or 1, 5, or 50 mg/kg of melatonin, respectively, for 4 weeks. Treatment with 5 mg/kg per day or 50 mg/kg per day of melatonin significantly increased bone mineral density (BMD; by 36%, p < 0.005) and bone mass (bone volume per tissue volume [BV/TV] by 49%, p < 0.01, and trabecular thickness [Tb.Th] by 19%, p < 0.05). This treatment significantly reduced bone resorption parameters (i.e., osteoclast surface [Oc.S/bone surface {BS}] by 74%, p < 0.05, and osteoclast number [N.Oc/BS] by 76%, p < 0.005) but did not increase histomorphometric bone formation parameters (i.e., bone formation rate [BFR/BS], mineral apposition rate [MAR], and osteoid volume [OV/TV]), indicating that melatonin increases bone mass predominantly through suppression of bone resorption. Melatonin (1–500 μM) in vitro caused dose-dependent reduction (p < 0.001 for each) in the number and area of resorption pits formed by osteoclasts derived from bone marrow cells but not those formed by isolated rabbit osteoclasts. Because RANKL increases, while osteoprotegerin (OPG) serves as a soluble decoy receptor for RANKL to inhibit osteoclast formation and activity, the effect of melatonin on the expression of RANKL and OPG in mouse MC3T3-E1 osteoblastic cells was investigated. Melatonin (5–500 μM) increased in a dose-dependent manner and reduced the mRNA level of RANKL and both mRNA and protein levels of OPG in MC3T3-E1 cells (p < 0.001 for each). In summary, these findings indicated for the first time that melatonin at pharmacologic doses in mice causes an inhibition of bone resorption and an increase in bone mass. These skeletal effects probably were caused by the melatonin-mediated down-regulation of the RANKL-mediated osteoclast formation and activation.
Effect of Pregnancy on Bone Mineral Density and Biochemical Markers of Bone Turnover in a Patient With Juvenile Idiopathic Osteoporosis
Authors: Black AJ , Reid R , Reid DM , Macdonald AG , Fraser WD
Published: April 2006

Juvenile idiopathic osteoporosis (JIO) is rare, presenting with vertebral fractures in the immediate prepubertal years; however, recovery is normally observed. We report the case of a 19-year-old pregnant woman previously diagnosed with JIO. She experienced three vertebral fractures in the third trimester of pregnancy. She delivered by caesarean section at 38 weeks gestation. Spinal bone mineral density decreased by 25%, hip bone mineral density by 10%, and forearm bone mineral density by 3% during pregnancy. Bone resorption markers, free pyridinoline and deoxypyridinoline (fPYD and fDPD), were elevated at baseline and markedly increased during pregnancy (fPYD/fDPD at 0, 10, 15, 20, and 28 weeks and immediately postpartum: 36.2/11.5, 52.9/15.8, 54.3/13.3, 51.1/13.3, 90/21.8, and 95.6/22.7 nmol/mmol creatinine, respectively) The bone formation marker, bone-specific alkaline phosphatase (BSAP), was within the reference range at baseline and increased in the third trimester. (BSAP at 0, 10, 15, 20, and 28 weeks and immediately postpartum: 20.5, 18.3, 17.7, 19.8, 26.9, and 30.0 U/liter, respectively). Parathyroid hormone (PTH) was measured by two methods to assess the possible effect of PTH fragments. PTH(1–84) (Roche) showed little change during the pregnancy, whereas the Nichols assay [(1–84) and(7–84) PTH fragment], revealed increases paralleling the changes in bone resorption. This young woman's bone turnover showed an exaggerated response to pregnancy, with bone resorption predominating over formation. PTH fragments may have partially mediated this effect.
Alendronate Interacts With the Inhibitory Effect of 1,25(OH)2D3 on Parathyroid Hormone-Related Protein Expression In Human Osteoblastic Cells
Authors: Gómez-García L , Esbrit P , Carreño L , Sabando P , García-Flores M , Martinez ME
Published: April 2006

The bisphosphonate alendronate is a potent inhibitor of bone resorption by its direct action on osteoclasts. In addition, there is some data suggesting that alendronate could also inhibit bone resorption indirectly by interacting with osteoblasts. Parathyroid hormone-related protein (PTHrP) produced by osteoblasts and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] are regulators of bone remodeling, which have interrelated actions in these cells. In this study, we assessed whether alendronate can affect PTHrP expression in the presence or absence of 1,25(OH)2D3 in human primary osteoblastic (hOB) cells from trabecular bone. Cell total RNA was isolated, and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was carried out using human PTHrP-specific primers. PTHrP in the hOB cell-conditioned medium was analyzed by a specific immunoradiometric assay. We found that PTHrP mRNA and secreted PTHrP were maximally inhibited by 10−8-10−6 M of 1,25(OH)2D3 treatment within 8–72 h in hOB cells. Alendronate (10−14-10−8 M) modified neither PTHrP mRNA nor PTHrP secretion, although it consistently abrogated the decrease in PTHrP production induced by 1,25(OH)2D3 in these cells. On the other hand, alendronate within the same dose range did not affect either the vitamin D receptor (VDR) mRNA or osteocalcin secretion, with or without 1,25(OH)2D3, in hOB cells. The inhibitory effect of alendronate on the 1,25(OH)2D3-induced decrease in PTHrP in these cells was mimicked by the calcium ionophore A23187 (5 × 10−6 M), while it was eliminated by 5 × 10−5 M of nifedipine. Furthermore, although alendronate alone failed to affect [Ca2+]i in these cells, it stimulated [Ca2+]i after pretreatment of hOB cells with 10−8 M of 1,25(OH)2D3, an effect that was abolished by 5 × 10−5 M of nifedipine. These results show that alendronate disrupts the modulatory effect of 1,25(OH)2D3 on PTHrP production in hOB cells. Our findings indicate that an increase in calcium influx appears to be involved in the mechanism mediating this effect of alendronate.
In Vitro Demonstration of Cell-to-Cell Interaction in Growth Plate Cartilage Using Chondrocytes Established From p53−/− Mice
Authors: Nakamata Takeharu , Aoyama Tomoki , Okamoto Takeshi , Hosaka Taisuke , Nishijo Koichi , Nakayama Tomitaka , Nakamura Takashi , Toguchida Junya
Published: April 2006

Three clonal cell lines (MMR14, MMR17, and MMR32) were established from the costal cartilage derived from p53−/− mice. Expression profiles of cartilage-related molecules in MMR14 and MMR17 were compatible with those in cells of the hypertrophic zone. Prolonged in vitro culture induced the expression of calcification-related genes in both cell lines, but calcified nodules were observed only in MMR14. The expression profile of cartilage-related molecules in MMR32 was compatible with that of cells in the perichondrium, with high expression levels of decorin, bone morphogenetic protein-3, and parathyroid hormone-related peptide (PTHrP). When MMR14 was co-cultured with an equal amount of MMR32 without direct contact, the nodule formation was completely inhibited, whereas no such inhibition was observed when MMR14 was co-cultured with MMR17, indicating that soluble factors produced by MMR32 were responsible for the inhibition. Blocking the effects of PTHrP by either antagonizing peptide or neutralizing antibody against PTHrP failed to rescue the inhibitory effects of MMR32, and no increase of the cyclic adenosine monophosphate production in MMR14 was observed when co-cultured with MMR32, suggesting that soluble factors other than PTHrP produced by MMR32 were responsible for the inhibition of terminal differentiation of hypertrophic chondrocytes. This report is the first to show cell-to-cell interaction in the growth plate using cell lines, which will be useful material to investigate the regulatory mechanism of chondrocyte differentiation.
Three Novel Mutations in SQSTM1 Identified in Familial Paget's Disease of Bone
Authors: Johnson-Pais Teresa L , Wisdom Julie H , Weldon Korri S , Cody Jannine D , Hansen Marc F , Singer Frederick R , Leach Robin J
Published: April 2006

Mutations in Sequestosome 1 (SQSTM1) have been shown to segregate with familial Paget's disease of bone (PDB). We examined the coding sequence of SQSTM1 in five PDB pedigrees and found three novel mutations clustered around the C-terminal ubiquitin associated domain. Disruptions of the C-terminal domain of SQSTM1 seem to be a leading cause of familial PDB.

Introduction: The characteristic features of Paget's disease of bone (PDB) are caused by focal areas of excessive and uncoordinated bone remodeling. A total of seven genetic loci (PDB1-PDB7) have been reported to be associated with the disease. The gene for Sequestosome 1 (p62; SQSTM1) has been identified as the causative gene for PDB3 in numerous French-Canadian families and families predominantly of British descent. To date, a total of three mutations, all affecting the ubiquitin-associated domain of SQSTM1, have been identified: a single 1215 C to T (P392L) transversion in exon 8, a T insertion in exon 8 (E396X), and a G to A mutation at the splice junction of exon 7 (IVS7 + 1).

Materials and Methods: DNA was isolated from blood collected from the members of five U.S. PDB pedigrees. Mutation analysis of the coding sequence of the SQSTM1 gene was performed on the proband and other key individuals in the pedigrees.

Results: Four of the five families had SQSTM1 mutations. Three of these mutations were novel: a single base deletion in exon 8 at position 1210 (1210delT) resulting in a premature stop codon at amino acid 394, a single C deletion in exon 8 at position 1215 (1215delC) also resulting in a premature stop codon at amino acid 394, and a single 1200 C to T (P387L) transversion in exon 7.

Conclusion: Noteworthy is the fact that these three SQSTM1 mutations, in addition to the three previously described mutations, are clustered near the C-terminal of the protein. These mutations may be acting in a dominant-negative fashion to disrupt the ubiquitin-binding function, which could result in abnormal activation of the NF-κB pathway and the subsequent activation of the osteoclasts. These findings imply that SQSTM1 mutations may play a role in the majority of familial PDB in the United States.
Osteoblastic Tartrate-Resistant Acid Phosphatase: Its Potential Role in the Molecular Mechanism of Osteogenic Action of Fluoride
Authors: Lau K-H William , Baylink David J
Published: April 2006

Although type 5 TRACP is recognized as a histochemical and biochemical marker of osteoclasts, there is evidence that bone forming cells, osteoblasts, and osteocytes also express a type 5 TRACP. Accordingly, an osteoblastic type 5 TRACP has been purified from human osteoblasts and from bovine cortical bone matrices. Comparison of biochemical properties of osteoblastic type 5 TRACP with those of osteoclastic type 5 TRACP suggests that osteoblastic type 5 TRACP is a different isoenzyme from osteoclastic type 5 TRACP. Two properties of osteoblastic type 5 TRACP may be relevant to its physiological functions: (1) it acts as a protein-tyrosine phosphatase (protein tyrosine phosphorylation) under physiologically relevant conditions, and (2) it is sensitive to inhibition by clinically relevant concentrations of fluoride. Because fluoride is a stimulator of osteoblastic proliferation and differentiation and a potent osteogenic agent and because protein tyrosine phosphorylation plays an important regulatory role in cell proliferation and differentiation, these unique properties and other evidence summarized in this review led to the proposal that the osteogenic action of fluoride is mediated, at least in part, by the fluoride-mediated inhibition of osteoblastic type 5 TRACP/protein tyrosine phosphorylation, which leads to a stimulation of osteoblast proliferation and differentiation, and subsequently, an increase in bone formation.
Repetitive, Negligible Force Reaching in Rats Induces Pathological Overloading of Upper Extremity Bones
Authors: Barr Ann E , Safadi Fayez F , Gorzelany Irene , Amin Mamta , Popoff Steven N , Barbe Mary F
Published: April 2006

Work-related repetitive motion disorders are costly. Immunohistochemical changes in bones resulting from repetitive reaching and grasping in 17 rats were examined. After 3–6 weeks, numbers of ED1+ macrophages and osteoclasts increased at periosteal surfaces of sites of muscle and interosseous membrane attachment and metaphyses of reach and nonreach forelimbs. These findings indicate pathological overloading leading to inflammation and subsequent bone resorption.

Introduction: Sixty-five percent of all occupational illnesses in U.S. private industry are attributed to musculoskeletal disorders arising from the performance of repeated motion, yet the precise mechanisms of tissue pathophysiology have yet to be determined for work-related musculoskeletal disorders. This study investigates changes in upper extremity bone tissues resulting from performance of a voluntary highly repetitive, negligible force reaching and grasping task in rats.

Materials and Methods: Seventeen rats reached an average of 8.3 times/minute for 45-mg food pellets for 2 h/day, 3 days/week for up to 12 weeks. Seven rats served as normal or trained controls. Radius, ulna, humerus, and scapula were collected bilaterally as follows: radius and ulna at 0, 3, 4, 5, 6, and 12 weeks and humerus and scapula at 0, 4, and 6 weeks. Bones were examined for ED1-immunoreactive mononuclear cells and osteoclasts. Double-labeling immunohistochemistry was performed for ED1 (monocyte/macrophage lineage cell marker) and TRACP (osteoclast marker) to confirm that ED1+ multinucleated cells were osteoclasts. Differences in the number of ED1+ cells over time were analyzed by ANOVA.

Results: Between 3 and 6 weeks of task performance, the number of ED1+ mononuclear cells and osteoclasts increased significantly at the periosteal surfaces of the distal radius and ulna of the reach and nonreach limbs compared with control rats. These cells also increased at periosteal surfaces of humerus and scapula of both forelimbs by 4–6 weeks. These cellular increases were greatest at muscle attachments and metaphyseal regions, but they were also present at some interosseous membrane attachments. The number of ED1+ cells decreased to control levels in radius and ulna by 12 weeks.

Conclusions: Increases in ED1+ mononuclear cells and osteoclasts indicate that highly repetitive, negligible force reaching causes pathological overloading of bone leading to inflammation and osteolysis of periosteal bone tissues.
Bone Mineral and Collagen Quality in Humeri of Ovariectomized Cynomolgus Monkeys Given rhPTH(1–34) for 18 Months
Authors: Paschalis Eleftherios P , Burr David B , Mendelsohn Richard , Hock Janet M , Boskey Adele L
Published: April 2006

A recent study of ovariectomized monkeys, treated with recombinant human parathyroid hormone (rhPTH)(1–34) at 1 or 5 mg/kg/day for 18 months or for 12 months followed by 6 months withdrawal from treatment, showed significant differences in the geometry and histomorphometry of cortical bone of the midshaft humerus. To determine the extent to which the rapid bone turnover and cortical porosity induced by rhPTH(1–34) in ovariectomized monkeys modified mineral content, mineral crystal maturity and collagen maturity (cross-link distribution) in the cortical periosteal and endosteal regions, cross-sections of the cortical bone of the mid-humerus, were examined using Fourier transform infrared imaging (FTIRI). FTIRI analyses demonstrated that rhPTH(1–34) altered bone mineral and collagen properties in a dose-dependent manner. Mineral crystal maturity and collagen cross-link ratio (pyridinoline/dehydro-dihydroxylysinonorleucine) on both endosteal and periosteal surfaces decreased relative to ovariectomized animals, consistent with new bone formation. These changes were partially sustained after withdrawal of the higher dose of rhPTH(1–34), suggesting a prolonged after-effect on bone properties for at least two bone remodeling cycles. In conclusion, treatment of ovariectomized monkeys with rhPTH(1–34) had significant effects on cortical bone mineral-to-matrix ratio, mineral crystal maturity, and collagen cross-link ratio. These were fully reversible when the 1-μg rhPTH(1–34) treatment was withdrawn, but only partially reversed when the 5-μg rhPTH(1–34) dose was withdrawn.
S 12911-2 Inhibits Osteoclastic Bone Resorption In Vitro
Authors: Takahashi N , Sasaki T , Tsouderos Y , Suda T
Published: April 2006

The potential anti-osteoporotic activity of the strontium compound, S12911, was tested on osteoclast-like cells and on cultured fetal mouse long bones. From 1 mM Sr2+, S12911 reduced both basal and stimulated bone resorption by decreasing osteoclast activity and ruffled border formation.

The aim of this study was to evaluate the effects of S 12911-2 on osteoclastic bone resorption using in vitro systems. Osteoclast-like cells, produced in vitro by co-culture of mouse bone marrow cells with primary osteoblasts, were allowed to settle on dentine slices, and the area of resorption pits formed after 48 h was measured using an image analysis system. S 12911-2, at a minimal active concentration of 1 mM Sr2+, significantly reduced pit formation by these cells (p < 0.05). Pretreatment of slices for 48 h with S 12911-2 (5 mM Sr2+) did not produce appreciable inhibition of resorption. Bone resorption in cultured fetal mouse long bones was assessed by measuring the release of pre-incorporated45calcium. S 12911-2 inhibited resorption in control cultures (18.9%, p ≤ 0.05) and in bones cultured with the active form of vitamin D3 [1,25(OH)2D3] (44.5%, p ≤ 0.05). S 12911-2 had no effect on the number of osteoclasts observed histochemically in longitudinal sections prepared from fetal mouse long bones. Electron microscopy of mouse long bones treated with S 12911-2 (3 mM Sr2+) showed osteoclasts with clear zones facing the bone surface, but without well-developed ruffled borders; untreated bones contained osteoclasts with normal ruffled borders. These results indicate that S 12911-2 inhibits osteoclast activity. This effect is directly linked to the presence of strontium, is effective on basal and stimulated resorption, and involves a decrease in ruffled border formation by osteoclasts.
Study Design in Osteoporosis: A European Perspective
Authors: Kanis Ja , Alexandre J-M , Bone Hg , Abadie E , Brasseur D , Chassany O , Durrleman S , Lekkerkerker Jff , Caulin F
Published: April 2006

The advent of effective agents for the treatment of osteoporosis has led to the view that placebo-controlled trials to test new agents for efficacy are no longer appropriate. Rather, studies of superiority, equivalence, or non-inferiority have been recommended. Such studies require very large sample sizes, and the burden of osteoporotic fracture in a trial setting is substantially increased. Studies of equivalence cannot be unambiguously interpreted because the variance in effect of active comparator agents is too large in osteoporosis. If fracture studies are required by regulatory agencies, there is still a requirement for placebo-controlled studies, although perhaps of shorter duration than demanded at present.
Zoledronic Acid Prevents Osteopenia and Increases Bone Strength in a Rabbit Model of Distraction Osteogenesis
Authors: Little David G , Smith Nicholas C , Williams Paul R , Briody Julie N , Bilston Lynne E , Smith Elisabeth J , Gardiner Edith M , Cowell Christopher T
Published: April 2006

Prolonged healing times and stress-shielding osteopenia remain problematic in distraction osteogenesis. In this study of 30 rabbits, zoledronic acid increased regenerate volume, mineralization, and tibial strength and prevented osteopenia over a 6-week period. Translation to the clinical setting, if safe, could improve outcomes in distraction osteogenesis in children.

Introduction: Because the external fixators for limb lengthening and reconstruction are designed to control the positions of bone fragments accurately, they also produce stress-shielding effects on the forming regenerate and surrounding bone. Osteopenia, leading to refracture and limitations on rehabilitation, are common consequences, potentially increasing morbidity and detracting from final clinical outcome.

Materials and Methods: We examined the effect of zoledronic acid on distraction osteogenesis in 42 immature male NZW rabbits. The model chosen results in reliable regenerate formation and stress-shielding osteopenia. Fourteen animals received either Saline, zoledronic acid 0.1 mg/kg at surgery (ZOL), or another dose 2 weeks postoperatively (Redosed ZOL). Rabbits underwent DXA for bone mineral content and bone mineral density in regenerate and surrounding segments of operated and contralateral tibias. After death at 6 weeks, 30 pairs of tibias underwent quantitative computerized tomography (QCT) and four-point bend testing, and 12 were examined by histomorphometry. The study was powered at 0.8 to show differences of 1.3 SDs for mineral and mechanical parameters.

Results: Osteopenia observed in tibias of the Saline group was absent in ZOL and Redosed ZOL tibias, the latter exhibiting higher bone mineral density and bone mineral content over contralateral regions (p < 0.01). Regenerate bone mineral content was higher in ZOL and Redosed ZOL versus Saline groups at 4 and 6 weeks (p < 0.01). Cross-sectional area was 49% and 59% greater at 6 weeks in ZOL and Redosed ZOL regenerates compared with the Saline group (p < 0.01). ZOL and Redosed ZOL tibias were 29% and 89% stronger by four-point bending than the Saline group (p < 0.01). Histomorphometry in the regenerate of ZOL and Redosed ZOL groups revealed higher trabecular bone volume and trabecular number compared with the Saline group (p < 0.001).

Conclusions: Zoledronic acid administration led to significantly greater bone area, mineral content, strength, and trabecular number with reduced stress-shielding osteopenia in this model of distraction osteogenesis. These data suggest that intraoperative and postoperative zoledronic acid administration could improve outcomes in children undergoing limb lengthening.
Morphological Determinants of Femoral Strength in Growth Hormone-Deficient Transgenic Growth-Retarded (Tgr) Rats
Authors: Evans Baj , Warner JT , Elford C , Evans SL , Laib A , Bains RK , Gregory JW , Wells T
Published: April 2006

The extent to which childhood GHD affects adult fracture risk is unclear. We measured femoral strength in adult transgenic growth-retarded rats as a model of GHD. Long-term, moderate GHD was accompanied by endocrine and morphometric changes consistent with a significant reduction in femoral strength.

Introduction: Childhood growth hormone deficiency (GHD) is associated with osteopenia, but little is known about its effects on subsequent adult bone strength and fracture risk.

Materials and Methods: We have therefore measured femoral strength (failure load measured by three-point bending) in a new model of moderate GHD, the transgenic growth-retarded (Tgr) rat at 15, 22–23, and 52 weeks of age, and have quantified potential morphological and endocrine determinants of bone strength.

Results: Skeletal growth retardation in Tgr rats was accompanied by a sustained reduction in the anterior-posterior diameter of the femoral cortex, whereas mid-diaphyseal cortical wall thicknesses were largely unaltered. Total femoral strength was significantly impaired in Tgr rats (p < 0.01), and this impairment was more pronounced in males than females. Compromised bone strength in Tgr rats could not be accounted for by the reduction in mechanical load (body weight) and was not caused by impairment of the material properties of the calcified tissue (ultimate tensile stress), despite marked reductions in femoral mineral density (areal bone mineral density; p < 0.001). Microcomputerized tomographical analysis revealed significant modification of the architecture of trabecular bone in Tgr rats, with reductions in the number and thickness of trabeculae (p < 0.05) and in the degree of anisotropy (p < 0.01). The marked reduction in plasma insulin-like growth factor-1 in Tgr rats was accompanied by the development of high circulating leptin levels (p < 0.01).

Conclusion: These results show that the changes in endocrinology and bone morphology associated with long-term moderate GHD in Tgr rats are accompanied by changes consistent with a significant reduction in the threshold for femoral fracture.
Dopamine D1Activation Potentiates Striatal NMDA Receptors by Tyrosine Phosphorylation-Dependent Subunit Trafficking
Authors: Hallett Penelope J. , Spoelgen Robert , Hyman Bradley T. , Standaert David G. , Dunah Anthone W.
Published: April 2006

Interactions between dopaminergic and glutamatergic afferents in the striatum are essential for motor learning and the regulation of movement. An important mechanism for these interactions is the ability of dopamine, through D1receptors, to potentiate NMDA glutamate receptor function. Here we show that, in striatal neurons, D1receptor activation leads to rapid trafficking of NMDA receptor subunits, with increased NR1 and NR2B subunits in dendrites, enhanced coclustering of these subunits with the postsynaptic density scaffolding molecule postsynaptic density-95, and increased surface expression. The dopamine D1receptor-mediated NMDA receptor trafficking is blocked by an inhibitor of tyrosine kinases. Blockers of tyrosine phosphatases also induce NMDA subunit trafficking, but this effect is nonselective and alters both NR2A- and NR2B-containing receptors. Furthermore, tyrosine phosphatase inhibition leads to the clustering of tyrosine-phosphorylated NR2B subunit along dendritic shafts. Our findings reveal that D1receptor activation can potentiate striatal NMDA subunit function by directly promoting the surface insertion of the receptor complexes. This effect is regulated by the reciprocal actions of protein tyrosine phosphatases and tyrosine kinases. Modification of these pathways may be a useful therapeutic target for Parkinson’s disease and other basal ganglia disorders in which abnormal function of striatal NMDA receptors contributes to the symptoms of the diseases.
In VivoMagnetic Resonance Imaging and Semiautomated Image Analysis Extend the Brain Phenotype forcdf/cdfMice
Authors: Bock Nicholas A. , Kovacevic Natasa , Lipina Tatiana V. , Roder John C. , Ackerman Susan L. , Henkelman R. Mark
Published: April 2006

Magnetic resonance imaging and computer image analysis in human clinical studies effectively identify abnormal neuroanatomy in disease populations. As more mouse models of neurological disorders are discovered, such an approach may prove useful for translational studies. Here, we demonstrate the effectiveness of a similar strategy for mouse neuroscience studies by phenotyping mice with the cerebellar deficient folia (cdf) mutation. Usingin vivomultiple-mouse magnetic resonance imaging for increased throughput, we imaged groups ofcdfmutant, heterozygous, and wild-type mice and made an atlas-based segmentation of the structures in 15 individual brains. We then performed computer automated volume measurements on the structures. We found a reduced cerebellar volume in thecdfmutants, which was expected, but we also found a new phenotype in the inferior colliculus and the olfactory bulbs. Subsequent local histology revealed additional cytoarchitectural abnormalities in the olfactory bulbs. This demonstrates the utility of anatomical magnetic resonance imaging and semiautomated image analysis for detecting abnormal neuroarchitecture in mutant mice.
You Crack Me Up!
Authors: beauchemin raymond
Published: April 2006

The Confréérie mondiale de les chevaliers de l'omelette gééante (World Fraternity of Knights of the Giant Omelet) spreads good cheer in several countries of the French-speaking world through the making and sharing of giant omelets. The tradition began in 1973 in Bessièères, France, where the townspeople fed indigent families in town. The practice of making a giant omelet soon spread to Frééjus, France; Malmedy, Belgium, and other cities with francophone histories: Dumbééa, New Caledonia; Granby, Quebec, and Abbeville, Louisiana. Each omelet has a regional flavor. The Louisiana omelet is influenced by Cajun and Creole cooking traditions. In Belgium, the omelet is made with pork lard. The recipe for Granby's more traditional omelet is familiar to most Quebecers: eggs, salt, parsley, thyme, pepper, scallions, and olive oil. In this case: fifteen thousand eggs, four liters of salt, five thousand scallions, and twenty liters of extra-virgin olive oil. The omelet is calculated to serve ten thousand.
Interaction and the Standardized Survey Interview: The Living Questionnaire
Authors: Darnell Regna
Published: April 2006

Interaction and the Standardized Survey Interview: The Living Questionnaire By Hannecke Houtkoop‐Steenstra. Cambridge. Cambridge University Press. 2000.
Sociolinguistic Theory: Linguistic Variation and Its Social Significance, 2nd edition
Authors: Salzmann Zdenek
Published: April 2006

Sociolinguistic Theory: Linguistic Variation and Its Social Significance, 2nd edition By J. K. Chambers. Maiden, MA. Blackwell Publishers. 2003.
Recentering the Middle School Classroom as a Vibrant Learning Community: Students, Literacy, and Technology Intersect
Authors: Grisham Dana L. , Wolsey Thomas D.
Published: April 2006

Technology reshapes our thinking about learning in multiple ways. This article proposes that middle school students can use asynchronous online discussions to improve their responses to literature, increase their engagement with the classroom community, and recenter the classroom around student voices. Working in small groups, students read the same novel. They are prompted to post their responses to the young adult literature in a closed, egalitarian online network.

The authors examined online transcripts, interviewed students, and observed lesson sequences in eighth‐grade humanities classrooms over three years. They found that threaded discussions helped these middle school students to

Engage with and learn new literacies

Examine literature through a more critical lens

Socially construct knowledge to create a more authentic community of learners

The authors also found that the role of the teacher is transformed by technology to scaffold instruction through participation in online conversations.
Crossover Interactions for Grain Yield in Multienvironmental Trials of Winter Wheat
Authors: Mishra R. , Baenziger P. Stephen , Russell W. Ken , Graybosch Robert A. , Baltensperger David D. , Eskridge Kent M.
Published: April 2006

Crossover interactions (COIs) are changes in ranks among cultivars across environments. Breeders are concerned about COIs because their frequency affects how well rankings from one environment predict rankings in another environment. This research was undertaken to determine the frequency and distribution of COIs for grain yield within years in two regional trials of winter wheat (Triticum aestivum L.). The trials were in Nebraska and in the south‐central USA (SCUS). Each trial had four environments per year, and results from 1998, 1999, and 2000 were considered. Significance of COI for each pair of lines in each pair of environments within years was determined by a t test with an interaction‐wise Type 1 error rate. Grain yield varied significantly across environments in both trials in all years, and in the within‐year analyses the line × environment interaction was always highly significant. In the Nebraska trial, the frequency of COIs was less than expected by chance only in one pair of environments in 1 yr. Nonetheless, because estimates suggested the line × environment × year variance was substantially greater than the line × environment variance, this significant occurrence of COIs did not support breeding for local adaptation. In the SCUS trial, a lower frequency of COIs occurred than in the Nebraska trial. In both trials, frequency of COIs in a pair of environments was not closely related to the difference in mean yield between those environments, which raised the usefulness of categorizing environments as low‐stress or as high‐stress for the purpose of selection.
Litter Decomposition and Mineralization in Bahiagrass Pastures Managed at Different Intensities
Authors: Dubeux J. C. B. , Sollenberger L. E. , Interrante S. M. , Vendramini J. M. B. , Stewart R. L.
Published: April 2006

Plant litter is an important nutrient pool in grassland ecosystems. Management practices affect litter quality and may affect nutrient dynamics in pastures by altering the rates of nutrient mineralization and immobilization. The effect of management intensity on litter decomposition and nutrient disappearance was evaluated in a litter bag study on continuously stocked ‘Pensacola’ bahiagrass (Paspalum notatum Flügge) pastures growing on Pomona and Smyrna sands. Treatments were three management intensities: Low (40 kg N ha−1yr−1 and 1.3 animal units [AU, one AU = 500 kg live weight] ha−1 stocking rate [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). Litter relative decomposition rate (k) was greater for High (0.0030 g g−1 d−1) than Low (0.0016 g g−1 d−1). Litter N, acid detergent insoluble N (ADIN), and lignin concentrations were greater for High than the other intensities at the end of the 168‐d incubation period because of faster decomposition of soluble compounds. Across management intensities, approximately one‐half of litter N remaining at the end of the incubation period was bound to acid detergent fiber (ADF). Net N mineralization through 128 d of incubation was only 200 to 300 g kg−1 of total N. Increasing management intensity resulted in faster litter turnover and greater nutrient release, but nutrient release from litter was small and significant quantities of nutrients were immobilized even under the most intensive management.
Planting Density Influences Disease Incidence and Severity of Sclerotinia Blight in Peanut
Authors: Maas Andrea L. , Dashiell Kenton E. , Melouk Hassan A.
Published: April 2006

Sclerotinia blight, caused by Sclerotinia minor Jagger, has become one of the major limiting factors in peanut (Arachis hypogaea L.) production. The objectives of this research were to evaluate the effects of plant spacing on disease incidence and severity of Sclerotinia blight in peanut research plots, to measure the level of apparent resistance at different seeding rates, and to determine which methods would produce clearest selection criteria in space‐planted breeding plots. Four peanut cultivars, Tamspan 90, Southwest Runner, Okrun, and Flavor Runner 458, were evaluated in field plots at four plant spacings (6, 15, 30, and 46 cm) in 2003 and 2004. Increased plant spacing improved sensitivity of disease incidence based determination of cultivar resistance but did not increase mean incidence significantly. Disease severity reached the highest level at the widest plant spacing. Final disease incidence provided excellent differentiation of genotypes with different levels of resistance and required the least amount of labor as compared with other methods of disease assessment.
Political Progress of a Paralyzed Liberal: The Community Dramas of John Arden
Authors: Trussler Simon
Published: April 2006

John Arden has been a bête-noire for middlebrows and a blue-eyed boy for intellectuals ever since Serjeant Musgrave's Dance got its first critical drubbing at the Royal Court Theatre in October 1959. But until recently Arden's reception has had little to do with political or ethical sympathies. The most conservative critics have been ready to go into raptures over Wesker's william-morrisy socialism or Orton's freebooting sexuality: and such playwrights are welcome to declare cold war on the establishment till kingdom come, as well it may. They have, it is assumed, the decency to stand up and be counted: the sabbatical critics therefore sink back into their stalls to do the counting, handing out awards to promising playwrights as if to bright but bolshy sixth-formers who'll soon learn the right side of their bread to butter. But with Arden the talent-spotters never used to know where they were: turning his own declared pacifism topsy-turvy in Musgrave one minute, the next he'd be suggesting that the action of Armstrong's Last Goodnight, a play about medieval Scotland in dog-gaelic, was tangential to the Congolese civil war.
Beginning at Zero: Notes on Cinema and Society
Authors: Rocha Glauber
Published: April 2006

Like every other culture in this technologydominated world, Brazilian culture shows the influence of cinema. Film arbitrates life-styles, activates the imagination with its fantasies, and shapes moral life. Yet it is impossible to speak of the cinema in its Brazilian context without referring to North American film, whose influence and aggressiveness distributes North American culture throughout the world so that audiences now expect from all films only those images they are accustomed to seeing in Hollywood cinema.

The Brazilian public, which is economically and culturally much closer to the United States than to Europe, has also based its images of life on North. American films. A vicious circle: when most Brazilians make films, they make them “a la Americana,” and it is primarily for this reason that Brazilian spectators try to make any Brazilian film they view into a Brazilian film “a la Americana.”
Malaysian Ma'yong Theatre
Authors: Malm William P.
Published: April 2006

The Ma'yong theatre of Malaysia, though little known outside the province of Kelantan where it once flourished, is a rare example of a court entertainment which changed into a popular performance within the relatively brief period of about fifty years. Ma'yong, now performed only two or three times a year by wives of rice farmers in the remote villages of Kelantan, carries little evidence of its court origins; however, the magical propitiatory function which seems to have been associated with it from the beginning is still recognized. Furthermore, Ma'yong is unique in that all the leading roles, both male and female, are taken by women, while only the parts of the servant-clowns, or peran (generally two in a given play), are played by men. This introduction to Ma'yong is based on a three-month expedition I made in 1968 to record this theatre and its music on video tape.
Caste, Politics, and Art
Authors: Perinbanayagam R. S.
Published: April 2006

Indian civilization is made up of many strands, woven together by the invasions, assimilations, and proselytizings which have characterized its history and prehistory. Generally, however, elements of the Sanskritic culture brought in by Aryan invaders (conjecturally from the Middle East) around 1500 B.C. are dominant, though the farther one gets from the northern regions of India, the less apparent this dominance becomes. The question whether the culture of southern India is a remnant of the pre-Aryan civilization of India or also was imported has never been resolved. However, regional differences in culture within the framework of a Sanskritic civilization are not disputed, nor is the fact that southern India is less Sanskritic in culture than northern India.

Such differences manifest themselves in a variety of customs, artifacts, arts, languages, and rituals.
Self-Use in Actor Training
Authors: Clay Jack
Published: April 2006

For the actor, the right use of self is the only sure basis for the expressive use of self.

Such a statement seems to me to summarize a trend in actor training in this country today. Soon after the Second World War, the Stanislavski “methodists,” led by Lee Strasberg, taught us important lessons in creative process, quite transforming our acting style. We crystalized a technique built on creative responsiveness, the mark always of good acting. Presumably these lessons are now an unforgettable part of our training.

However, those of us who were students of Strasberg—or some of the other great acting teachers of that time, like Alvina Krause or Sanford Meisner—and who went on to teach another generation of young actors, sooner or later found ourselves facing more fundamental problems. These dealt with what is usually called voice and body work.
The Stanislavsky System in Russia
Authors: Poggi Jack
Published: April 2006

When I watched some acting classes in Moscow in 1969, it soon became apparent that my conception of the Stanislavsky System (based on books and on the work in some New York studios) had little bearing on what I was actually seeing. This was a refreshing experience. I had reached a point in my own work at which I could no longer accept, at least without considerable modification, some of Stanislavsky's pet theories. I was agreeably surprised to find that the ideas I most objected to were either largely ignored in practice or interpreted in a way that I could agree with, and that the actual way of work was one I could admire and learn from.
Commedia and the Actor
Authors: Mazzone-Clementi Carlo
Published: April 2006

Although we can conjecture about commedia in a historical framework, we cannot know what it was like. There are no existing scripts, no photos. There are only a few paintings, a few sparse descriptions, and a horde of mostly untranslated scenarios. Yet, a great interest in commedia continues. Anyone can open the drawer marked commedia dell'arte, but, having opened it, how does one know what to choose from it? For some, commedia means a dusty reincarnation of the postures and poses of a Callot, charming in print, but deadly on the stage. The magnetic appeal of commedia, for me, has been to rediscover the magic of the performer: how he worked, what he did, and to some extent, why he did it, consciously or not. The only possible approach is an inductive one. We must begin where we are.
Criticism: Four Faults
Authors: Kirby Michael
Published: April 2006

Theatrical criticism, as we know it, is primitive and naive, arrogant, and immoral. We accept that this should be so because it always has been so. Mental and cultural inertia justifies nothing, however. Criticism should be changed.

There are two aspects to criticism: the passing of value judgments and analysis. It is the former that will be questioned here. Indeed, the word “criticism” will be used to refer specifically to the act of publishing statements of value. (One definition given by Webster is “a finding fault; censuring; disapproval.”) Thus, the evaluative and analytical functions will be considered as separate and distinct; “analysis” will be opposed to “criticism” rather than being included in it. In these terms, it is not merely a change that will be asked of criticism. Criticism as value judgment is a harmful anachronism and should be eliminated completely.
It's About Time
Authors: Gordon David
Published: April 2006

Modern dance makes more choreographers, I believe, than ballet does. A conventional modern dance company is a very small group working with the specific ideas of a single artist. There are a limited number of these situations and an extraordinary number of dancers in training. It is not always difference in ideology or the compulsive need to explore a single vision that produces a new modern dance choreographer. It is simply expedient to create a personal marketplace in which to exhibit one's wares. The leniency with which modern dance has come to treat the eccentricities of body structure and performance as opposed to continued restrictions in ballets, allows for great variety in style and stature. But the small company, with its specific vision, often does not. So, choreography, for some of us, is self-defense.

When I began performing publicly in other peoples’ work, I had a fairly goodlooking body, (though not a very flexible one), good height, good balance, and no training.
Structuralism in Theatre: The Prague School Contribution
Authors: Deák František
Published: April 2006

Between 1928 and 1948 in Czechoslovakia, a prolific group of linguists and theoreticians of literature, theatre and music, known as the Prague school, worked out the first systematic structuralist-semiotic approach to the study of art. (The semiotics of art—the study of art as a system of signs—was actually established by Jan Mukařovský's programmatic statement “Art as a Semiotic Fact” at the Eighth International Congress of Philosophy in Prague in 1934.) Concentrating primarily on the problems of poetry and literature, structuralists gradually expanded their interest to include theatre, film, visual arts, and music as well as the problems of general theory and esthetics.
Meredith Monk: Performer-Creator
Authors: Koenig Carole
Published: April 2006

It is as the creator and director of her own highly innovative works that Meredith Monk is perhaps best known. Since graduating in 1964 from Sarah Lawrence College, she has channeled her energies into deVising performance pieces that fuse, in varying balances, a “triangle” of dance, theatre, and music into a single unified whole. Monk has described her works in such terms as “a live movie,” “a theatre cantata,” an “opera epic.” She is interested in the way that the forms of dance, music, and theatre work against and with each other “and then the form that comes out of these crossings. That's why I have different names for different pieces. Because I'm always surprised at what the balance comes out to be myself. And then after it's finished, I sort of have to figure out what it is.”
The Theatrical Journey of Giuliano Scabia
Authors: De Marinis Marco
Published: April 2006

In April-May 1972, in twelve different towns in Abruzzo, Giuliano Scabia carried out a series of “actions” with young people; each lasted three days. The project, Perhaps a Dragon Will Be Born, was supported by the Teatro Stabile of I'Aquila and by other local cultural organizations. Both in the planning stage and in the organizational stage, these actions showed many of the elements that characterized Scabia's subsequent work: an open laboratory, an empty scheme, puppets, daily newspapers, posters, meetings, great images, etc.
Semiotics of Theatrical Performance
Authors: Eco Umberto
Published: April 2006

According to Jorge Luis Borges, Abulgualid Mohammed Ibn Ahmed Ibn Mohammahd Ibn Rushd, better known as Averroes, was thinking—something like one thousand years ago, more or less—about a difficult question concerning Aristotle's Poetics. As you probably know, Averroes was a specialist on Aristotle, mainly on the Poetics. As a matter of fact, Western civilization had lost this book and had rediscovered it only through the mediation of Arab philosophers. Averroes did not know about theatre. Because of the Muslim taboo on representation, he had never seen a theatrical performance. At least, Borges, in his short story The Quest of Averroes, imagines our philosopher wondering about two incomprehensible words he had found in Aristotle, namely “tragedy” and “comedy.” A nice problem, since Aristotle's Poetics is nothing else but a complex definition of those two words, or at least of the first of them.
Structuralist Film
Authors: Kirby Michael
Published: April 2006

Many structuralist plays could be made quite directly into structuralist films. The time or durational structures of the live performances could simply be filmed, with or without the filter of changed camera angle and variation of frame size, to make a movie. Even the three-dimensional spatial structures important to most structuralist plays could be represented or “translated” in film. (For example, two alternating and interwoven stories separated spatially on stage could be distinguished in a film by using different color filters for each; spatial progressions could be translated into color progressions; etc.) Yet it would be impossible to make most structuralist films into live performances. Structuralist films tend to exploit the high degree of mechanical control inherent in the medium, a control that is not possible in live performance. Thus an analysis of selected films that may be called structuralist should tell us something about the media of film and theatre and about structuralism itself.