bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in Bone Density, Body Composition, Physical Activity, and Diet Between Child Gymnasts and Untrained Children 7-8 Years of Age
Authors: Zanker Cl , Gannon L , Cooke Cb , Gee Kl , Oldroyd B , Truscott Jg
Published: April 2006

Strategies that enhance the acquisition of bone mass may be protective against osteoporosis. BMD was compared in 20 artistic gymnasts (10 boys; 10 girls) and 20 untrained children ages 7-8 years. Higher regional values of BMD were observed in female gymnasts than untrained girls. If retained to adulthood, this higher BMD may protect skeletal integrity in later life.

Strategies that enhance the acquisition of bone mass in children may assist with the prevention of osteoporosis. This study explored the effects of regular high-impact and weight-bearing activity before the age of 7 years on total and regional bone mineral density (BMD). Twenty artistic gymnasts (10 boys and 10 girls) and 20 untrained children, 7-8 years of age, were recruited. The untrained children were matched to gymnasts by sex, height, weight, and age. Female gymnasts trained 8-10 h per week and had trained regularly for 3-4 years. Male gymnasts trained 4-6 h per week and had trained for 1-2 years. Measurements of bone mineral density were made using DXA for total body BMD (TBBMD); lumbar spine, both areal (aSBMD) and volumetric (vSBMD); total spine; pelvis; arms; and legs. Significant mean differences (8-10%) in aSBMD, vSBMD, arm BMD, and TBBMD were observed between female gymnasts and untrained girls (p < 0.05: aSBMD, vSBMD, and TBBMD body mass (BM); p < 0.01: arm BMD). A nonsignificant trend toward a higher TBBMD/BM and arm BMD was observed in male gymnasts compared with untrained boys. Trends toward a higher BMD within the pelvis, legs, and total spine were also observed in gymnasts. There were no differences in total and regional BMD between untrained boys and untrained girls. The results suggest that gymnastics training before the age of 7 years enhances the acquisition of bone mass at selected skeletal sites. The magnitude of this enhancement seems to be linked to the cumulative volume of such training. If retained during adolescence and young adulthood, a surfeit of bone acquired through high-impact and weight-bearing activity in early childhood may protect skeletal integrity in later life.
Linkage of Structure at the Proximal Femur to Chromosomes 3, 7, 8, and 19
Authors: Koller Dl , White Ke , Liu G , Hui Sl , Conneally Pm , Johnston Cc , Econs Mj , Foroud T , Peacock M
Published: April 2006

Risk for osteoporotic fracture is determined in part by femoral structure, which is under genetic control. We conducted a genome scan in 638 sister-pairs for structure phenotypes. Significant evidence of linkage was detected with several chromosomal regions, including confirmation of our prior linkage findings.

Bone strength and resistance to fracture at the proximal femur is determined in part by structural variables. We previously reported that several structural variables, including pelvic axis length, femur axis length, femur head width, and femur midshaft width, had significant or suggestive linkage to regions of chromosomes 3, 4, 5, 7, 9, 17, and 19 in a sample of 309 white premenopausal sister pairs. We now report the results of a genome-wide linkage analysis of femoral structure variables in 437 white and 201 black healthy premenopausal sister pairs, of which 191 white pairs overlapped with our previously published sample. Multipoint quantitative linkage analysis was performed using microsatellite markers genotyped throughout the genome. In the current sample, linkage of femoral structure to chromosomes 3, 7, and 19 was confirmed in the white sister pairs, and a new linkage to chromosome 8 was identified. There was linkage at chromosome 3 to femoral head width (logarithm of the odds [LOD] = 5.0) and femur shaft width (LOD = 3.6). On chromosome 19, there was linkage to femoral neck axis length (LOD = 3.2); on chromosome 7, to femoral head width (LOD = 5.0); and on chromosome 8, to femoral head width (LOD = 6.0). The current findings emphasize the importance of increasing sample size to replicate linkage findings and identify new regions of linkage.
Human Adult Chondrocytes Express Hepatocyte Growth Factor (HGF) Isoforms but Not HGF: Potential Implication of Osteoblasts on the Presence of HGF in Cartilage
Authors: Guévremont Melanie , Martel-Pelletier Johanne , Massicotte Frédéric , Tardif Ginette , Pelletier Jean-Pierre , Ranger Pierre , Lajeunesse Daniel , Reboul Pascal
Published: April 2006

HGF is increased in human OA cartilage, possibly from Ob's. RT-PCR shows HGF isoforms are differently regulated between chondrocytes and Ob. A paracrine cross-talk between subchondral bone and cartilage may occur during OA.

Recently, hepatocyte growth factor (HGF) has been identified by immunohistochemistry in cartilage and more particularly in the deep zone of human osteoarthritic (OA) cartilage. By investigating HGF expression in cartilage, we found that chondrocytes did not express HGF; however, they expressed the two truncated isoforms, namely HGF/NK1 and HGF/NK2. Because the only other cells localized near the deep zone are osteoblasts from the subchondral bone plate, we hypothesized that they were expressing HGF. Indeed, we found that HGF was synthesized by osteoblasts from the subchondral bone plate. Moreover, OA osteoblasts produced five times more HGF than normal osteoblasts and almost no HGF/NK1, unlike normal osteoblasts. Because prostaglandin E2 (PGE2) and pro-inflammatory cytokines such as interleukin (IL)-1 and IL-6 are involved in OA progression, we investigated whether these factors impact HGF produced by normal osteoblasts. PGE2 was the only factor tested that was able to stimulate HGF synthesis. However, the addition of NS398, a selective inhibitor of cyclo-oxygenase-2 (COX-2) had no effect on HGF produced by OA osteoblasts. HGF/NK2 had a moderate stimulating effect on HGF production by normal osteoblasts, whereas osteocalcin was not modulated by either HGF or HGF/NK2. When investigating signaling routes that might be implicated in OA osteoblast-produced HGF, we found that protein kinase A was at least partially involved. In summary, this study raises the hypothesis that the HGF found in articular cartilage is produced by osteoblasts, diffuses into the cartilage, and may be implicated in the OA process.
RANKL Expression Is Related to the Differentiation State of Human Osteoblasts
Authors: Atkins Gerald J , Kostakis Panagiota , Pan Beiqing , Farrugia Amanda , Gronthos Stan , Evdokiou Andreas , Harrison Kate , Findlay David M , Zannettino Andrew Cw
Published: April 2006

Human osteoblast phenotypes that support osteoclast differentiation and bone formation are not well characterized. Osteoblast differentiation markers were examined in relation to RANKL expression. RANKL expression was induced preferentially in immature cells. These results support an important link between diverse osteoblast functions.

Cells of the osteoblast lineage support two apparently distinct functions: bone formation and promotion of osteoclast formation. The aim of this study was to examine the relationship between these phenotypes in human osteoblasts (NHBC), in terms of the pre-osteoblast marker, STRO-1, and the mature osteoblast marker, alkaline phosphatase (AP), and the expression of genes involved in osteoclast formation, RANKL and OPG. The osteotropic stimuli, 1α,25(OH)2vitamin D3 (vitD3) and dexamethasone, were found to have profound proliferative and phenotypic effects on NHBCs. VitD3 inhibited NHBC proliferation and increased the percentage of cells expressing STRO-1 over an extended culture period, implying that vitD3 promotes and maintains an immature osteogenic phenotype. Concomitantly, RANKL mRNA expression was upregulated and maintained in NHBC in response to vitD3. Dexamethasone progressively promoted the proliferation of AP-expressing cells, resulting in the overall maturation of the cultures. Dexamethasone had little effect on RANKL mRNA expression and downregulated OPG mRNA expression in a donor-dependent manner. Regression analysis showed that RANKL mRNA expression was associated negatively with the percentage of cells expressing AP (p < 0.01) in vitD3- and dexamethasone-treated NHBCs. In contrast, RANKL mRNA expression was associated positively with the percentage of STRO-1+ cells (p < 0.01). In NHBCs sorted by FACS based on STRO-1 expression (STRO-1bright and STRO-1dim populations), it was found that vitD3 upregulated the expression of RANKL mRNA preferentially in STRO-1bright cells. The results suggest that immature osteoblasts respond to osteotropic factors in a potentially pro-osteoclastogenic manner. Additionally, the dual roles of osteoblasts, in supporting osteoclastogenesis or forming bone, may be performed by the same lineage of cells at different stages of their maturation.
Linked Deficiencies in Extracellular PPi and Osteopontin Mediate Pathologic Calcification Associated With Defective PC-1 and ANK Expression
Authors: Johnson Kristen , Goding James , Van Etten Deborah , Sali Adnan , Hu Shou-Ih , Farley David , Krug Hollis , Hessle Lovisa , Millán José Luis , Terkeltaub Robert
Published: April 2006

Osteopontin and PPi both suppress hydroxyapatite deposition. Extracellular PPi deficiency causes spontaneous hypercalcification, yet unchallenged osteopontin knockout mice have only subtle mineralization abnormalities. We report that extracellular PPi deficiency promotes osteopontin deficiency and correction of osteopontin deficiency prevents hypercalcification, suggesting synergistic inhibition of hydroxyapatite deposition.

Nucleotide pyrophosphatase phosphodiesterase (NPP) isozymes including PC-1 (NPP1) function partly to generate PPI, a physiologic calcification inhibitor. PPi transport is modulated by the membrane channel protein ANK. Spontaneous articular cartilage calcification, increased vertebral cortical bone formation, and peripheral joint and intervertebral ossific ankylosis are associated with both PC-1 deficiency and expression of truncated ANK in ank/ank mice. To assess how PC-1, ANK, and PPi regulate both calcification and cell differentiation, we studied cultured PC-1−/− and ank/ank mouse calvarial osteoblasts. PC-1−/− osteoblasts demonstrated ∼50% depressed NPP activity and markedly lowered extracellular PPi associated with hypercalcification. These abnormalities were rescued by transfection of PC-1 but not of the NPP isozyme B10/NPP3. PC-1−/− and ank/ank cultured osteoblasts demonstrated not only comparable extracellular PPi depression and hypercalcification but also marked reduction in expression of osteopontin (OPN), another direct calcification inhibitor. Soluble PC-1 (which corrected extracellular PPi and OPN), and OPN itself (≥15 pg/ml), corrected hypercalcification by PC-1−/− and ank/ank osteoblasts. Thus, linked regulatory effects on extracellular PPi and OPN expression mediate the ability of PC-1 and ANK to regulate calcification.
Gene Array Analysis of Bone Morphogenetic Protein Type I Receptor-Induced Osteoblast Differentiation
Authors: Korchynskyi Olexander , Dechering Koen J , Sijbers Anneke M , Olijve Wiebe , Ten Dijke Peter
Published: April 2006

The genomic response to BMP was investigated by ectopic expression of activated BMP type I receptors in C2C12 myoblast using cDNA microarrays. Novel BMP receptor target genes with possible roles in inhibition of myoblast differentiation and stimulation of osteoblast differentiation were identified.

Introduction: Bone morphogenetic proteins (BMPs) have an important role in controlling mesenchymal cell fate and mediate these effects by regulating gene expression. BMPs signal through three distinct specific BMP type I receptors (also termed activin receptor-like kinases) and their downstream nuclear effectors, termed Smads. The critical target genes by which activated BMP receptors mediate change cell fate are poorly characterized.

Materials and Methods: We performed transcriptional profiling of C2C12 myoblasts differentiation into osteoblast-like cells by ectopic expression of three distinct constitutively active (ca)BMP type I receptors using adenoviral gene transfer. Cells were harvested 48 h after infection, which allowed detection of both early and late response genes. Expression analysis was performed using the mouse GEM1 microarray, which is comprised of approximately 8700 unique sequences. Hybridizations were performed in duplicate with a reverse fluor labeling. Genes were considered to be significantly regulated if the p value for differential expression was less than 0.01 and inverted expression ratios per duplicate successful reciprocal hybridizations differed by less than 25%.

Results and Conclusions: Each of the three caBMP type I receptors stimulated equal levels of R-Smad phosphorylation and alkaline phosphatase activity, an early marker for osteoblast differentiation. Interestingly, all three type I receptors induced identical transcriptional profiles; 97 genes were significantly upregulated and 103 genes were downregulated. Many extracellular matrix genes were upregulated, muscle-related genes downregulated, and transcription factors/signaling components modulated. In addition to 41 expressed sequence tags without known function and a number of known BMP target genes, including PPAR-γ and fibromodulin, a large number of novel BMP target genes with an annotated function were identified, including transcription factors HesR1, ITF-2, and ICSBP, apoptosis mediators DRP-1 death kinase and ZIP kinase, IκBα, Edg-2, ZO-1, and E3 ligase Dactylin. These target genes, some of them unexpected, offer new insights into how BMPs elicit biological effects, in particular into the mechanism of inhibition of myoblast differentiation and stimulation of osteoblast differentiation.
Dietary n-3 Fatty Acids Decrease Osteoclastogenesis and Loss of Bone Mass in Ovariectomized Mice
Authors: Sun Dongxu , Krishnan Aparna , Zaman Khaliquz , Lawrence Richard , Bhattacharya Arunabh , Fernandes Gabriel
Published: April 2006

The mechanisms of action of dietary fish oil (FO) on osteoporosis are not fully understood. This study showed FO decreased bone loss in ovariectomized mice because of inhibition of osteoclastogenesis. This finding supports a beneficial effect of FO on the attenuation of osteoporosis.

Introduction: Consumption of fish or n-3 fatty acids protects against cardiovascular and autoimmune disorders. Beneficial effects on bone mineral density have also been reported in rats and humans, but the precise mechanisms involved have not been described.

Methods: Sham and ovariectomized (OVX) mice were fed diets containing either 5% corn oil (CO) or 5% fish oil (FO). Bone mineral density was analyzed by DXA. The serum lipid profile was analyzed by gas chromatography. Receptor activator of NF-κB ligand (RANKL) expression and cytokine production in activated T-cells were analyzed by flow cytometry and ELISA, respectively. Osteoclasts were generated by culturing bone marrow (BM) cells with 1,25(OH)2D3. NF-κB activation in BM macrophages was measured by an electrophoretic mobility shift assay.

Results and Conclusion: Plasma lipid C16:1n6, C20:5n3, and C22:6n3 were significantly increased and C20:4n6 and C18:2n6 decreased in FO-fed mice. Significantly increased bone mineral density loss (20% in distal left femur and 22.6% in lumbar vertebrae) was observed in OVX mice fed CO, whereas FO-fed mice showed only 10% and no change, respectively. Bone mineral density loss was correlated with increased RANKL expression in activated CD4+ T-cells from CO-fed OVX mice, but there was no change in FO-fed mice. Selected n-3 fatty acids (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]) added in vitro caused a significant decrease in TRACP activity and TRACP+ multinuclear cell formation from BM cells compared with selected n-6 fatty acids (linoleic acid [LA] and arachidonic acid [AA]). DHA and EPA also inhibited BM macrophage NF-κB activation induced by RANKL in vitro. TNF-α, interleukin (IL)-2, and interferon (IFN)-γ concentrations from both sham and OVX FO-fed mice were decreased in the culture medium of splenocytes, and interleukin-6 was decreased in sham-operated FO-fed mice. In conclusion, inhibition of osteoclast generation and activation may be one of the mechanisms by which dietary n-3 fatty acids reduce bone loss in OVX mice.
Dietary Calcium and Phosphorus Ratio Regulates Bone Mineralization and Turnover in Vitamin D Receptor Knockout Mice by Affecting Intestinal Calcium and Phosphorus Absorption
Authors: Masuyama Ritsuko , Nakaya Yumi , Katsumata Shinichi , Kajita Yasutaka , Uehara Mariko , Tanaka Shinya , Sakai Akinori , Kato Shigeaki , Nakamura Toshitaka , Suzuki Kazuharu
Published: April 2006

The effects of the dietary Ca and P ratio, independent of any vitamin D effects, on bone mineralization and turnover was examined in 60 VDRKO mice fed different Ca/P ratio diets. High dietary Ca/P ratio promoted bone mineralization and turnover with adequate intestinal Ca and P transports in VDRKO mice.

Introduction: To clarify the effects of the dietary calcium (Ca) and phosphorus (P) ratio (Ca/P ratio) on bone mineralization and turnover in null-vitamin D signal condition, vitamin D receptor knockout (VDRKO) mice were given diets containing different Ca/P ratios.

Materials and Methods: Five groups of 4-week-old VDRKO mice, 10 animals each, were fed diets for 4 weeks. Group 1 was wild-type littermate mice, fed the diet containing 0.5% Ca and P (Ca/P = 1). Group 2 was the control and was fed a similar diet (Ca/P = 1). Groups 3, 4, 5, and 6 were fed the following diets:0.5% Ca and 1.0% P (Ca/P = 0.5), 1.0% Ca and 1.0% P (Ca/P = 1), 1.0% Ca and 0.5% P (Ca/P = 2), and 0.5% Ca and 0.25% P (Ca/P = 2).

Results and Conclusions: Compared with group 2, serum calcium and phosphorus levels in groups 4–6 significantly increased. Serum parathyroid hormone levels increased in group 3 and decreased in group 5. The amounts of intestinal calcium absorption decreased in groups 3 and 4. Phosphorus absorption increased in group 3 and decreased in groups 4–6. Bone mineral content (BMC) and bone mineral density (BMD) of the femur in group 3 significantly decreased and increased in group 5. In the primary spongiosa of the proximal tibia, the trabecular bone volume (BV/TV) and osteoid thickness (O.Th) in group 3 significantly increased, and decreased in group 6. In groups 5 and 6, the numbers of the trabecular osteoclasts increased. In groups 2 and 4, and the secondary spongiosa was identified in 5 of 10 mice. In group 3, there was no secondary spongiosa in either mouse. Osteoid maturation time (OMT) significantly decreased, and bone formation rate (BFR/BS) increased in groups 4–6. These data indicate that the dietary Ca/P ratio regulates bone mineralization and turnover by affecting the intestinal calcium and phosphorus transports in VDRKO mice. They may suggest the existence of Ca/P ratio-dependent, vitamin D-independent calcium and phosphorus transport system in the intestine.
Irreversible Perforations in Vertebral Trabeculae?
Authors: Banse X , Devogelaer JP , Delloye C , Lafosse A , Holmyard D , Grynpas M
Published: April 2006

In human cancellous bone, osteoclastic perforations resulting from normal remodeling were generally considered irreversible. In human vertebral samples, examined by backscatter electron microscopy, there was clear evidence of bridging of perforation defects by new bone formation. Hence trabecular perforations may not be irreversible.

Introduction: Preservation of the trabecular bone microarchitecture is essential to maintain its load-bearing capacity and prevent fractures. However, during bone remodeling, the osteoclasts may perforate the platelike trabeculae and disconnect the structure. Large perforations (>100 μm) are generally considered irreversible because there is no surface on which new bone can be laid down. In this work, we investigated the outcome of these perforations on human vertebral cancellous bone.

Materials and Methods: Using backscatter electron microscopy, we analyzed 264 vertebral bone samples from the thoracic and lumbar spine of nine subjects (44–88 years old). Nine fields (2 × 1.5 mm) were observed on each block. Several bone structural units (BSUs) were visible on a single trabecula, illustrating a dynamic, historical aspect of bone remodeling. A bridge was defined as a single and recent BSU connecting two segments of trabeculae previously separated by osteoclastic resorption. They were counted and measured (length and breadth, μm).

Results and Conclusion: We observed 396 bridges over 2376 images. By comparison, we found only 15 microcalluses on the same material. The median length of the bridge was 165 μm (range, 29–869 μm); 86% being longer than 100 μm and 35% longer than 200 μm. Their breadth was 56 μm (range, 6–255 μm), but the thinnest were still in construction. Bridges were found in all nine subjects included in the study, suggesting that it is a common feature of normal vertebral bone remodeling. These observations support the hypothesis that perforation could be repaired by new bone formation. and hence, might not be systematically irreversible.
Association Between Vertebral Fracture and Increased Mortality in Osteoporotic Patients
Authors: Jalava Tarja , Sarna Seppo , Pylkkänen Liisa , Mawer Barbara , Kanis John A , Selby Peter , Davies Michael , Adams Judith , Francis Roger M , Robinson John , McCloskey Eugene
Published: April 2006

Determinants of mortality were studied in a prospective study of 677 women and men with primary or secondary osteoporosis. Prevalent vertebral fractures were associated with increased mortality, but other known predictors of mortality explain a significant proportion of the excess risk.

Introduction: In population studies, prevalent vertebral fractures are associated with increased mortality. It is unknown whether this excess mortality is related to low bone mineral density or its determinants or whether there is an additional component associated with fracture itself.

Methods: We studied 677 women and men with osteoporosis, 28–88 years old, of whom 352 had morphometrically determined vertebral fracture, to examine the risk and causes of mortality in patients with osteoporosis (defined densitometrically as a spine bone mineral density T-score < −2.5 and −3.0 for women and men, respectively, and/or one or more prevalent vertebral fractures without a history of significant trauma). The participants had enrolled in a double-blind placebo-controlled study in osteoporosis and were comprised of 483 women with postmenopausal osteoporosis, 110 women with secondary osteoporosis, and 84 men with osteoporosis of any cause. Demographics, medical history, and other measures of skeletal and nonskeletal health status were assessed at entry.

Results: During a median follow-up of 3.2 years, 37 (5.5%) participants died, with 31 of these deaths occurring in those with prevalent vertebral fractures. Compared with participants who did not have a prevalent vertebral fracture, those with one or more fractures had a 4.4-fold higher (95% CI, 1.85, 10.6) mortality rate. After adjustment for predictors for poor health—including number of medications, number of diseases, use of oral corticosteroids, alcohol intake, serum albumin and erythrocyte sedimentation rate (ESR), renal function, height, weight, gender, and age—the point estimate of risk remained elevated but was no longer statistically significant (hazard ratio, 2.4; 95% CI. 0.93, 6.23).

Conclusions: Prevalent vertebral fractures in osteoporotic patients are associated with increased mortality. Other known predictors of mortality can explain a significant proportion of the excess risk.
Absence of Marked Seasonal Change in Bone Turnover: A Longitudinal and Multicenter Cross-Sectional Study
Authors: Blumsohn Aubrey , Naylor Kim E , Timm Wolfram , Eagleton Alison C , Hannon Rosemary A , Eastell Richard
Published: April 2006

The effect of season on bone turnover is controversial. No information is available on seasonality of new serum markers of bone resorption. In this study, we have been unable to confirm findings of a marked wintertime increase in bone formation and resorption within the general population. Seasonality was assessed by cosinor analysis.

Introduction: We investigated the effect of season on seven markers of bone turnover in a longitudinal study (six men and six premenopausal women; age, 24–44 years) and a separate large population-based multicenter European study (n = 2780 women, Osteoporosis and Ultrasound Study [OPUS]).

Materials and Methods: Measurements included serum Crosslaps, procollagen type I N-terminal propeptide (PINP), osteocalcin (OC), and the N-telopeptide fragment of type I collagen in urine (NTX). Seasonality was assessed by cosinor analysis with Hotelling's T2 test.

Results: Serum 25(OH) vitamin D showed a marked seasonal rhythm. There was no significant seasonal component for any marker of bone turnover in the longitudinal analysis (cosinor analysis, p > 0.05). The percentage of within subject variance accounted for by any seasonal trend was very small for all markers (less than 2.5%). Less than 1% of the between-person variance was accounted for by seasonality in the cross-sectional analysis for all markers (n = 2780). There was a small but statistically significant summertime increase in OC and PINP in the healthy postmenopausal population after exclusions based on disease or medication use (remaining n = 1226, amplitudes 5.6% and 5.4%, respectively, p < 0.001).

Conclusions: We have been unable to confirm findings of a marked wintertime increase in bone formation and resorption within the general population. The absence of marked seasonality was irrespective of age, menopausal status, reported supplemental Vitamin D intake, age or geographical location. The small but statistically significant summertime increase in bone formation in this and other studies is unlikely to confound clinical interpretation of these measurements.
State-Dependent Cross-Linking of the M2 and M3 Segments: Functional Basis for the Alignment of GABAAand Acetylcholine Receptor M3 Segments
Authors: Jansen Michaela , Akabas Myles H.
Published: April 2006

Construction of a GABAAreceptor homology model based on the acetylcholine (ACh) receptor structure is complicated by the low sequence similarity between GABAAand ACh M3 transmembrane segments that creates significant uncertainty in their alignment. We determined the orientation of the GABAAM2 and M3 transmembrane segments using disulfide cross-linking. The M2 residues α1M266 (11′) and α1T267 (12′) were mutated to cysteine in either wild type or single M3 cysteine mutant (α1V297C, α1A300C to α1A305C) backgrounds. We assayed spontaneous and induced disulfide bond formation. Reduction with DTT significantly potentiated GABA-induced currents in α1T267C-L301C and α1T267C-F304C. Copper phenanthroline-induced oxidation inhibited GABA-induced currents in these mutants and in α1T267C-A305C. Intrasubunit disulfide bonds formed between these Cys pairs, implying that the α-carbon separation was at most 5.6 Å. The reactive α1M3 residues (L301, F304, A305) lie on the same face of an α-helix. The unresponsive ones (A300, I302, E303) lie on the opposite face. In the resting state, the reactive side of α1M3 faces M2-α1T267. In conjunction with the ACh structure, our data indicate that alignment of GABAAand ACh M3 requires a single gap in the GABAAM2–M3 loop. In the presence of GABA, oxidation of α1T267C-L301C and α1T267C-F304C had no effect, but oxidation of α1T267C-A305C caused a significant increase in spontaneous channel opening. We infer that, as the channel opens, the distance and/or orientation between M2-α1T267 and M3-α1A305 changes such that the disulfide bond stabilizes the open state. This begins to define the conformational motion that M2 undergoes during channel opening.
Host Response and Dysfunction in the CNS during Chronic Simian Immunodeficiency Virus Infection
Authors: Roberts Eleanor S. , Huitron-Resendiz Salvador , Taffe Michael A. , Marcondes Maria Cecilia G. , Flynn Claudia T. , Lanigan Caroline M. , Hammond Jennifer A. , Head Steven R. , Henriksen Steven J. , Fox Howard S.
Published: April 2006

CNS abnormalities can be detected during chronic human immunodeficiency virus (HIV) infection, before the development of opportunistic infections or other sequelae of immunodeficiency. However, although end-stage dementia caused by HIV has been linked to the presence of infected and activated macrophages and microglia in the brain, the nature of the changes resulting in the motor and cognitive disorders in the chronic stage is unknown. Using simian immunodeficiency virus-infected rhesus monkeys, we sought the molecular basis for CNS dysfunction. In the chronic stable stage, nearly 2 years after infection, all animals had verified CNS functional abnormalities. Both virus and infiltrating lymphocytes (CD8+ T-cells) were found in the brain. Molecular analysis revealed that the expression of several immune response genes was increased, includingCCL5, which has pleiotropic effects on neurons as well as immune cells.CCL5was significantly upregulated throughout the course of infection, and in the chronic phase was present in the infiltrating lymphocytes. We have identified an altered state of the CNS at an important stage of the viral–host interaction, likely arising to protect against the virus but in the long term leading to damaging processes.
Transport of Information along Unidimensional Layered Networks of Dissociated Hippocampal Neurons and Implications for Rate Coding
Authors: Feinerman Ofer , Moses Elisha
Published: April 2006

The ability of synchronous population activity in layered networks to transmit a rate code is a focus of recent debate. We investigate these issues using a patterned unidimensional hippocampal culture. The network exhibits population bursts that travel its full length, with the advantage that signals propagate along a clearly defined path. The amplitudes of activity are measured using calcium imaging, a good approximate of population rate code, and the distortion of the signal as it travels is analyzed. We demonstrate that propagation along the line is precisely described by information theory as a chain of Gaussian communication channels. The balance of excitatory and inhibitory synapses is crucial for this transmission. However, amplitude information carried along this layered neuronal structure fails within 3 mm, ∼10 mean axon lengths, and is limited by noise in the synaptic transmission. We conclude that rate codes cannot be reliably transmitted through long layered networks.
The Dopamine D2Receptor Regulates the Development of Dopaminergic Neurons via Extracellular Signal-Regulated Kinase and Nurr1 Activation
Authors: Kim Sung Yul , Choi Kyou Chan , Chang Min Seok , Kim Myoung Hwan , Kim Sa Yong , Na Young-Soon , Lee Jong Eun , Jin Byung Kwan , Lee Bong-Hee , Baik Ja-Hyun
Published: April 2006

Because the dopaminergic pathways in the midbrain have been closely associated with serious neuropsychiatric disorders, the elucidation of the mechanisms underlying dopaminergic neuronal development should provide some important clues for related disorders. In mice lacking the dopamine D2receptor (D2R−/−), stereological cell counting analysis showed that the number of mesencephalic tyrosine hydroxylase (TH) cells was significantly low during ontogeny, compared with that observed in wild-type (WT) mice, thereby indicating an alteration in dopaminergic neuronal development in the absence of D2R. The results of immunohistochemical and reverse transcription-PCR analyses revealed that the expression of Nurr1, an orphan nuclear receptor, as well as Ptx3 expression, was selectively reduced in D2R−/− mice during the embryonic stage. A reporter gene assay using the Nur response element linked to the luciferase reporter gene indicated that the stimulation of D2R results in the activation of the Nurr1-mediated reporter gene. This D2R-mediated Nur response element-dependent transcriptional activity was regulated via the activation of extracellular signal-regulated kinase (ERK). Furthermore, quinpirole treatment was shown to elicit an increase in the number of TH-positive neurons, as well as the neuritic extension of TH neurons, coupled with ERK activation and Nurr1 activation in the TH-positive neurons in primary mesencephalic cultures from WT mice. However, this regulation was not detected in the D2R−/− mice. These results suggest that signaling through D2R in association with Nurr1 using ERK, plays a critical role in mesencephalic dopaminergic neuronal development.
The Politics of Small Things, Left and Right
Authors: Goldfarb Jeffrey C.
Published: April 2006

Small personal interactions can have big political effects. In the 2004 campaigns, this process worked well for Howard Dean, but it worked even better for the Christian Right.
Do Markets Poison Intimacy?
Authors: Zelizer Viviana A.
Published: April 2006

Myth: economic activity corrupts intimate relations, and intimate relations make economic activity inefficient. Fact: people constantly mingle intimacy and economic activity without corruption.
"Staged" Rituals and "Veiled" Spells
Authors: Kang Yoonhee
Published: April 2006

This article analyzes shifting forms and meanings of two Petalangan traditional genres of verbal magic, a public healing ritual and a genre of personal magical spells, in the context of the Petalangan social marginalization. To explain why and how these two genres have changed differently, this article focuses on the roles of two different language ideologies, the referentialist and performativist views of language, in the mediation between the linguistic and social changes in Petalangan society. Against the prevailing assumption of a linear transition of language ideologies from the performativist to the referentialist view of language in accordance with social modernization, the transformations in the Petalangan magical genres reveal a multifaceted process of change in which multiple language ideologies have worked differently across the genres and contexts.
Framing Discourse
Authors: Ahlers Jocelyn C.
Published: April 2006

For many Native Americans, the use of English in identity performance is problematized by a connection with dominant culture; the use of Tribal languages does not perform a broader Native American identity. This article considers several examples of the public use of Native American languages by nonfluent speakers, showing that foregrounding the metacommunicative/pragmatic function of such language use over referential function highlights a broader Native American identity shared by speaker and audience and creates a discourse space in which a subsequent English speech event is understood by audience members to come from, and be informed by, a Native identity.
Silicon Literacies: Communication, Innovation, and Education in the Electronic Age By Ilana Snyder
Authors: Abrams Zsuzsanna I.
Published: April 2006

Silicon Literacies: Communication, Innovation, and Education in the Electronic Age By Ilana Snyder. ed. New York. Routledge. 2002.
The Miami‐Illinois Language
Authors: Berardo Marcellino
Published: April 2006

The Miami‐Illinois Language. By David J. Costa. Lincoln. University of Nebraska Press. 2003.
From Hand to Mouth: The Origins of Language
Authors: Reissland Nadja
Published: April 2006

From Hand to Mouth: The Origins of Language By Michael C. Corballis. Princeton. Princeton University Press. 2002.
“There's a Better Word”: Urban Youth Rewriting Their Social Worlds Through Poetry
Authors: Jocson Korina M.
Published: April 2006

Recent studies undertaken with sociocultural perspectives on literacy offer a framework through which to explore poetry in youth's lives. This article draws upon works within New Literacy Studies to provide a glimpse of urban high school youth's experiences in a unique program called Poetry for the People (P4P). It identifies some ways in which these experiences have been valuable in acquisition of writing skills, confidence in learning, self‐awareness, and development of social conscience. The view of poetry presented affirms the importance of students' voices in the writing and learning process. It highlights how acknowledging students' interests in and abilities to produce sophisticated poems can create different possibilities for enhancing students' literacy development. The import of poetry for young people's identities, in particular emergent identities as empowered citizens and writers, examined within the context of P4P advances current perspectives on how poetry can be used for effective writing instruction in and out of schools.
Reaction to Three Races of Fusarium Wilt in the Phaseolus vulgaris Core Collection
Authors: Brick Mark A. , Byrne Patrick F. , Schwartz Howard F. , Ogg J. Barry , Otto Kristin , Fall Amy L. , Gilbert Jeremy
Published: April 2006

Seven races of Fusarium oxysporum f. sp. phaseoli Kendrick and Snyder (Fop) cause Fusarium wilt (FW) disease of common bean (Phaseolus vulgaris L.). FW occurs worldwide and has recently become a serious disease in the central and western USA. The objectives of this research were to identify new sources of resistance to Fop, characterize the Central/South American (CA/SA) Phaseolus Core Collection for reaction to races 1, 4, and 5 Fop and determine if a previously reported sequence characterized amplified region (SCAR) molecular marker would be useful to identify resistance among accessions that make up the CA/SA Core Collection. Seedlings from the CA/SA Core Collection were screened for reaction by a root dip inoculation procedure. Among accessions evaluated for reaction to race 1 Fop, 21 were resistant, 47 intermediate, and 126 susceptible. Fifteen accessions were resistant to race 4, 61 intermediate, and 114 were susceptible. Nine accessions were resistant to both races 1 and 4, and five of the nine (PI 207373, PI 307802, PI 308908, PI 309877, PI 310842) were also resistant to race 5 Fop. All accessions resistant to races 1, 4, and 5 of Fop were characterized as Middle American, which suggests that resistance to multiple races of Fop should be more prevalent in germplasm from Middle America. The SCAR marker previously developed to identify a quantitative trait locus (QTL) associated with resistance to Fop was not associated with resistance in the Core Collection.
Tocopherol Content and Agronomic Performance of Soybean Lines with Reduced Palmitate
Authors: Scherder Curtis W. , Fehr Walter R. , Welke Grace A. , Wang Tong
Published: April 2006

Soybean [Glycine max (L.) Merr.] cultivars have been developed with reduced palmitate content that is controlled by the fap1 and fap3 alleles. One objective of our study was to compare the tocopherol content of reduced and normal palmitate lines with similar genetic backgrounds. A second objective was to compare the agronomic and seed traits of the two types of lines. Three single‐cross populations segregating for palmitate content were developed from which 20 reduced and normal palmitate lines were selected for evaluation at three environments during 2004. The mean total tocopherol of the reduced palmitate lines was 15% greater than the normal palmitate lines, and the line with the greatest total tocopherol in each population contained reduced palmitate. The mean seed yield of the reduced palmitate lines was 5.5% lower than the normal palmitate lines. There were significant differences between the two types of lines for other agronomic and seed traits; however, the significant genetic variation among lines of each type would permit the selection of reduced palmitate lines that were similar to normal palmitate lines for those traits. Use of the reduced palmitate trait would be advantageous to maximize the tocopherol content of soybean oil.
Aerosol Smoke and Smoke‐Water Stimulation of Seedling Vigor of a Commercial Maize Cultivar
Authors: Sparg S. G. , Kulkarni M. G. , van Staden J.
Published: April 2006

The effect of smoke as a germination cue is well documented. Recent developments in smoke technology have suggested that smoke also improves vigor. It has been reported that indigenous storage methods of South African maize landraces using smoke enhances seedling vigor. This present study highlights the effects of aerosol smoke and smoke–water on the germination and seedling vigor of a commercial maize cultivar, Zea mays L. var. PAN 6479. Various presoaking and smoking combinations were investigated. Treating seeds with aerosol smoke showed significant (p < 0.05) stimulatory effects on vigor. However, prolonged exposure to aerosol smoke resulted in reduced germination which was alleviated by rinsing the seeds. Furthermore, presoaking seeds before exposure to aerosol smoke also significantly (p < 0.05) reduced the inhibitory effect of prolonged smoking. The combination of presoaking and smoking had a significant (p < 0.05) improvement on the percentage germination. This study also showed that smoke has the potential to improve not only the percentage germination but also seedling vigor of commercially bred maize seeds.
Effects of Four Independent Low‐Phytate Mutations on Barley Agronomic Performance
Authors: Bregitzer Phil , Raboy Victor
Published: April 2006

The seed phosphorus storage compound phytic acid (myo‐inositol‐1,2,3,4,5,6‐heakisphosphate) is poorly utilized by nonruminant animals. Low Phytate (LP) crops, in which reductions of phytate are accompanied by increases in nutritionally available P, are in development and their utility will be enhanced by competitive agronomic performance. To assess the performance of LP barley (Hordeum vulgare L.), sets of sib lines that are homozygous wild type (WT), or homozygous for one of four independent low phytic acid mutations (lpa1‐1, lpa2‐1, lpa3‐1, and M955), were developed via backcrosses to Harrington. The WT sibsets performed similarly to the Harrington parent, suggesting that the major variable in these experiments was the presence or absence of the LP alleles. Under irrigation, M955, which has an extreme reduction in phytate, was associated with reduced yield and percentage plump kernels; all mutations except lpa2‐1 were associated with reduced test weight. In rain‐fed locations, all mutations were associated with reduced test weight and percentage plump kernels, and all except lpa1‐1 were associated with reduced yield. These results suggest that one component of yield loss in LP types is reduced stress tolerance. The performance of the lpa1‐1 mutation, which appears to be aleurone specific, suggests a potential strategy to avoid this source of yield loss: the use of genotypes where the desirable effect is limited to a target tissue, in this case the aleurone layer.
Biplot Analysis of Forage Combining Ability in Maize Landraces
Authors: Bertoia Luis , López César , Burak Ruggero
Published: April 2006

In Argentina, maize (Zea mays L.) hybrids selected for silage production and local adaptation are not available for most temperate regions where silage maize can be produced. This study sought maize landraces that could be used as germplasm sources to enhance forage yield and quality in warm temperate areas and emphasized eight landraces not previously selected for grain yield. These were crossed in a diallel mating design and the 28 F1 population hybrids, the eight parental populations, and four commercial hybrids were evaluated in four environments in Argentina for combining abilities and to determine heterotic patterns among germplasm sources, using a biplot diallel analysis. Significant midparent heterosis (MPH) was observed for ear yield (EY), stover yield (SY), and whole plant yield (WY). General combining ability (GCA) effects were significant for EY, SY, and WY. Specific combining ability (SCA) effects were not significant for any trait. The graphical representation offered by biplot analysis allowed a rapid and effective overview of GCA and SCA effects of the populations, their performance in crosses, as well as grouping patterns of similar genotypes. Significant variation among checks was observed for EY and SY. On average, commercial hybrids had greater EY, but lower SY, than landraces and population hybrids. Some landrace crosses showed superior or similar WY than commercial checks, indicating the breeding potential of the evaluated germplasm.
Ecogeography and Demography of Cicer judaicum Boiss., a Wild Annual Relative of Domesticated Chickpea
Authors: Ben‐David Roi , Lev‐Yadun Simcha , Can Canan , Abbo Shahal
Published: April 2006

Chickpea (Cicer arietinum L.) is a major pulse crop in the Indian subcontinent and other world regions and is characterized by narrow adaptation relative to other cool season food legumes. Comparative ecophysiology employing closely related wild species is a powerful tool to broaden the understanding of the genetic and physiological basis of crop adaptation. However, meager data are available on the ecological preferences of annual wild Cicer species. Moreover, the geographic range, its size, shape, and boundaries as well as its internal structure have never been studied for any of the wild Cicer taxa, thereby limiting our understanding of Cicer biology. Accordingly, this work focused on Israeli C. judaicum Boiss. a wild annual relative of chickpea. We defined the range of the species across the Mediterranean zone of Israel, characterized the ecogeographical profile of its habitats and studied two populated sites at the macro‐ and microsite levels in terms of plant density, frequency, and niche physical characteristics. Throughout the survey area the species is mostly confined to stony and rocky niches where competition with more aggressive annuals is small. This habitat preference dictates a patchy distribution pattern at all levels, from local niche to the region and beyond.
The Black Arts Movement
Authors: Neal Larry
Published: April 2006

The Black Arts Movement is radically opposed to any concept of the artist that alienates him from his community. Black Art is the aesthetic and spiritual sister of the Black Power concept. As such, it envisions an art that speaks directly to the needs and aspirations of Black America. In order to perform this task, the Black Arts Movement proposes a radical reordering of the western cultural aesthetic. It proposes a separate symbolism, mythology, critique, and iconology. The Black Arts and the Black Power concept both relate broadly to the Afro-American's desire for self-determination and nationhood. Both concepts are nationalistic. One is concerned with the relationship between art and politics; the other with the art of politics.
Peer Gynt, Naturalism, and The Dissolving Self
Authors: Fjelde Rolf
Published: April 2006

Modern drama resembles a child half wise, in both knowing and not knowing its own father. By familiar usage, consecrated in the textbooks, Ibsen is “the father of modern drama”; the phrase instantly evokes the companion term “naturalism,” followed perhaps by a dim after-image of A Doll House, the consensual firstborn of our present theatrical age. This familiar view of the father has its partial truth, yielding certain academic rewards. It invites the editing of anthologies laid out on a taut straight line from Ibsen to Arthur Miller, with occasional detours into the essential non-realistic styles; or, if the anthologist is less sympathetic to Naturalism, it allows a backward glance at Hedda Gabler before one takes off for the real beginnings of modern drama somewhere in the volcanic foothills of Strindberg, finally to disappear in the farthest out thickets of the Grove Press.
Father's Day: In Search of 6 Characters in Search of an Author
Authors: Bentley Eric
Published: April 2006

A man has a wife and a male child. He also has a male secretary. Between the wife and the secretary there arises what the husband considers an understanding of a harmless sort. He wants to help them in some way, but whenever he speaks to them they exchange a significant look that seems to ask how they should receive what he says if they are not to annoy him. But this itself annoys him. He ends up firing the secretary. Then he sends the wife after him. In the wife's view, he fairly throws her into the secretary's arms; and the pair set up house together. The husband, however, does not lose interest in the wife. His continued interest, indeed, though he considers it “pure” (that is: asexual) is a source of embarrassment to the former secretary.