bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction of Three-dimensional Framework with 1,8-Anthrylene and Butadiynylene Building Units: Synthesis and Properties of Cyclic Tetramers
Authors: Goichi Michio , Toyota Shinji
Published: June 2006

As a new type of π-conjugated macrocycles, 1,8-anthrylene–butadiynylene cyclic tetramers were synthesized by metal-catalyzed oxidative coupling reactions. The fluorescence spectrum of the nonsubstituted derivative indicated partial formation of an excimer in the excited state. The macrocyclic structure undergoes rapid interconversion between two enantiomeric diamond prism structures. These spectroscopic and structural features are compared with those of ethynylene analogues.
Bio-inspired Programmable Self-assembly on DNA Templates
Authors: Tanaka Kentaro , Shionoya Mitsuhiko
Published: June 2006

Besides the biological importance of DNA as storage of genetic information, DNA is a smart molecule to assemble functional units since it is possible to use sequences of nucleobases to encode molecularly assembled systems in a predetermined fashion over a wide range in size. This review highlights recent advance in precise control of molecular assembly on DNA templates directed towards functionalized materials.
Synthesis of a Water-soluble Iridium(III) Complex with pH and Metal Cation Sensitive Photoluminescence
Authors: Konishi Koji , Yamaguchi Hiroyasu , Harada Akira
Published: June 2006

A water-soluble iridium complex with bulky ligands was synthesized. Photoluminescence intensities of this iridium complex were stronger in basic aqueous solutions than that in organic solvents, and they were found to depend on pH and additive metal ions in its aqueous solution.
Reversible Photoswitching Liquid-phase Adsorption on Azobenzene Derivative-grafted Mesoporous Silica
Authors: Maeda Kazuyuki , Nishiyama Takashi , Yamazaki Tsutomu , Suzuki Takeyuki , Seki Takahiro
Published: June 2006

Mesoporous silica tethered with alkyl chain-headed azobenzene derivatives exhibits reversible photoswitching behavior in liquid-phase adsorption of an octabutoxyphthalocyanine (OBPc) probe molecule on alternating ultraviolet and visible light irradiation.
New Approach to the Delamination of Layered Manganese Oxide
Authors: Cui Yanhua , Liu Zong-Huai , Wang Mingzhen , Ooi Kenta
Published: June 2006

A new method for the delamination of layered manganese oxide is successfully developed in a low-concentration solution of tetramethylammonium hydroxide by an ultrasonic treatment.
Double Fluorescence-labeling Study on Genus Albizzia Using a Set of Fluorecence-labeled Leaf-movement Factors to Identify the Spatial Distribution of Their Receptors
Authors: Nakamura Yoko , Matsubara Akira , Okada Masahiro , Kumagai Tsutomu , Ueda Minoru
Published: June 2006

We synthesized rhodamine-labeled leaf-opening factor of genus Albizzia. We carried out double fluorescence-labeling study on genus Albizzia using rhodamine-labeled leaf-opening factor and fluorescein-labeled leaf-closing factor. This study showed that both probes bound the same motor cell. These results indicated that each motor cell had both receptors for leaf-opening and leaf-closing factors.
Structure of Organic Thin Films Grown on Surface-modified Tantalum Oxide
Authors: Onoki Ryo , Abe Shigeomi , Ueno Keiji , Nakahara Hiroo , Saiki Koichiro
Published: June 2006

We fabricated an ordered monolayer film of a long-chain fatty acid or a perfluorofatty acid onto an anodized tantalum oxide (Ta2O5) amorphous surface by the Langmuir–Blodgett (LB) method, and grew a pentacene or C60 thin film on it. Remarkable improvements of morphology and crystallinity of the organic thin films were observed on the CH3-terminated monolayer film of the fatty acid.
Finely-tuned Blue-phosphorescent Iridium Complexes Based on 2-Phenylpyridine Derivatives and Application to Polymer Organic Light-emitting Device
Authors: Takizawa Shin-ya , Echizen Hidenori , Nishida Jun-ichi , Tsuzuki Toshimitsu , Tokito Shizuo , Yamashita Yoshiro
Published: June 2006

We have developed new blue-phosphorescent iridium complexes based on 2-phenylpyridine derivatives with pertinent substituents and an ancillary ligand to accomplish selective tuning of the HOMO and LUMO levels toward high energy gap: A polymer light-emitting device doped with the blue phosphor was fabricated to show blue emission.
Formation Process of Platelet Nanocomposites with Zinc Hydroxide and Sodium Dodecyl Sulfate Prepared by Laser Ablation in Solution
Authors: Usui Hiroyuki , Sasaki Takeshi , Koshizaki Naoto
Published: June 2006

Layered zinc hydroxide nanocomposites (Zn-NC) were prepared by laser ablation of Zn in an aqueous solution of sodium dodecyl sulfate (SDS) with various ablation times and laser fluences. At the fluence of 6.7 J/cm2, the rectangular Zn-NC was obtained by 10 min ablation. Rectangular structures were found with different stages of Zn filling at the fluence of 2.0 J/cm2. These results suggest that an SDS monohydrate with rectangular shape acts as the template for Zn-NC formation.
Photosolubilization of Polyolefinsulfone Containing Side-chain Oxime Ester Groups
Authors: Yaguchi Hiroaki , Sasaki Takeo , Matsuda Minoru
Published: June 2006

A novel polyolefinsulfone bearing a photobase generator in a side-chain was synthesized via radical polymerization of an olefin monomer in liquefied sulfur dioxide. The polyolefinsulfone was photochemically solubilized in an aqueous solution of 0.012 M HCl.
mRNA localization to the mitochondrial surface allows the efficient translocation inside the organelle of a nuclear recoded ATP6 protein
Authors: Kaltimbacher Valérie , Bonnet Crystel , Lecoeuvre Gaëlle , Forster Valérie , Sahel José-Alain , Corral-Debrinski Marisol
Published: June 2006

As previously established in yeast, two sequences within mRNAs are responsible for their specific localization to the mitochondrial surface—the region coding for the mitochondrial targeting sequence and the 3′UTR. This phenomenon is conserved in human cells. Therefore, we decided to use mRNA localization as a tool to address to mitochondria, a protein that is not normally imported. For this purpose, we associated a nuclear recoded ATP6 gene with the mitochondrial targeting sequence and the 3′UTR of the nuclear SOD2 gene, which mRNA exclusively localizes to the mitochondrial surface in HeLa cells. The ATP6 gene is naturally located into the organelle and encodes a highly hydrophobic protein of the respiratory chain complex V. In this study, we demonstrated that hybrid ATP6 mRNAs, as the endogenous SOD2 mRNA, localize to the mitochondrial surface in human cells. Remarkably, fusion proteins localize to mitochondria in vivo. Indeed, ATP6 precursors synthesized in the cytoplasm were imported into mitochondria in a highly efficient way, especially when both the MTS and the 3′UTR of the SOD2 gene were associated with the re-engineered ATP6 gene. Hence, these data indicate that mRNA targeting to the mitochondrial surface represents an attractive strategy for allowing the mitochondrial import of proteins originally encoded by the mitochondrial genome without any amino acid change in the protein that could interfere with its biologic activity.
Family and coping factors in the differentiation of childhood anxiety and depression
Authors: Vulić‐Prtorić Anita , Macuka Ivana
Published: June 2006

The purpose of this investigation was to explore whether specific contextual (perception of family relationships) and personal (coping strategies) factors are more likely to be associated with anxiety or depression. The research was conducted on a sample of 331 children and adolescents ranging in age from 10 to 16 years who completed measures of the anxiety symptoms, depressive symptoms, coping strategies, and family interactions. Data were analysed according to gender differences. Among family variables, perceived father rejection was found to be best predictor of anxiety, and father and mother rejection, together with family satisfaction, was best predictor for the depression. Avoidance is a coping strategy that best predicts anxiety, and expressing feelings is a significant predictor of depression. This research strongly indicates that problems in family interactions are more associated and better predictors of depression than anxiety. Results support the argument that the two disorders are distinct and that they are characterized by unique coping and family profiles. Knowledge that anxiety and depression could be distinguished on the basis of family and coping variables may facilitate clinical assessment and treatment planning.
God as other, God as self, God as beyond: A cognitive analytic perspective on the relationship with God
Authors: Marsh Robert , Low James
Published: June 2006

A case is made for the importance of working with religious material psychotherapeutically whilst at the same time being attentive to the pitfalls that may arise in doing so. A clinical vignette is presented illustrating some of these difficulties. Connections between constructions of self, other, and God are discussed using reciprocal roles, a concept from cognitive analytic therapy (CAT). A perspective offering a multiple and ‘voiced’ nature of self is explored; parallels are drawn with descriptions of God; and therapeutic implications are discussed.
Poor me versus bad me paranoia and the instability of persecutory ideation
Authors: Melo Sara Sigmaringa , Taylor Jayne L. , Bentall Richard P.
Published: June 2006

Objectives. To investigate whether there are two stable types of paranoia, ‘poor me’ and ‘bad me’, as described by Trower and Chadwick (1995), and whether beliefs about the deservedness of persecution are associated with psychological measures.

Methods. In‐patients experiencing persecutory delusions were assigned either to ‘poor me’ (PM) or ‘bad me’(BM) groups, according to their rating of a perceived deservedness scale, which was repeated on subsequent assessments. Participants were assessed for depression (BDI); construction of the self (Self‐to‐Others Scale); autonomy and sociotropy (PSI); perceived parental behaviour (PBI); attributional style (ASQ) and, meaningful daily events (DEI, devised for the study). A healthy control group was also assessed.

Results. Many patients' perceived deservedness of persecution varied across time, so that some patients were PM at one point in time but BM at another. BM paranoia was associated with high levels of depression. PM and BM patients groups both scored higher than the controls on the subscales of Self‐to‐Others Scale and on the PSI. PM patients exhibited a marked self‐serving bias on the ASQ, and reported less parental care on the PSI, compared to the BM patients. Both groups reported less PBI mother care than the controls. BM patients reported more failure events than PM patients or controls. PM patients reported more loss of control events than the than BM patients and controls.

Conclusions. PM and BM paranoia may represent separate phases of an unstable phenomenon. The findings are consistent with an attributional account of paranoid thinking.
The Stalking and Harassment Behaviour Scale: Measuring the incidence, nature, and severity of stalking and relational harassment and their psychological effects
Authors: Turmanis Simon A. , Brown Robert I.
Published: June 2006

Objectives. Assessing the incidence, nature, severity, and psychological effects of stalking and relational harassment for victims is a difficult task and conceptual issues have hampered previous research, making it difficult for psychologists and clinicians to predict psychological sequelae for victims and develop appropriate treatments.

Design. A new scale was developed that included a measure of participants' levels of subjective distress/disturbance to aid clinicians to better assess the incidence, nature, and level of stalking and/or relational harassment for victims.

Methods. From a pool of 204 participants from Newcastle University and two business offices, it was possible to differentiate 159 persons who experienced harassment and/or stalking from the remainder who were not distressed or disturbed by such attention.

Results. Stalked and/or harassed individuals were separated into five separate groups based on their levels of stalking and five score ranges with qualitative labels, devised to aid in the interpretation of victims' levels of stalking scores. Those with higher levels of stalking reported increased levels of helplessness, symptoms of anxiety, PTSD, and depression.

Conclusion. The results indicate the importance of accommodating a subjective component in the measurement and assessment of stalking and harassment. Future directions for the development and use of the new scale are discussed.
Dysregulation of the BMP-p38 MAPK Signaling Pathway in Cells From Patients With Fibrodysplasia Ossificans Progressiva (FOP)
Authors: Fiori Jennifer L , Billings Paul C , de la Peña Lourdes Serrano , Kaplan Frederick S , Shore Eileen M
Published: June 2006

FOP is a disabling disorder in which skeletal muscle is progressively replaced with bone. Lymphocytes, our model system for examining BMP signaling, cannot signal through the canonical Smad pathway unless exogenous Smad1 is supplied, providing a unique cell type in which the BMP–p38 MAPK pathway can be examined. FOP lymphocytes exhibit defects in the BMP–p38 MAPK pathway, suggesting that altered BMP signaling underlies ectopic bone formation in this disease.

Introduction: Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by progressive heterotopic ossification of connective tissues. Whereas the primary genetic defect in this condition is unknown, BMP4 mRNA and protein and BMP receptor type IA (BMPRIA) protein are overexpressed in cultured lymphocytes from FOP patients, supporting that altered BMP signaling is involved in this disease. In this study, we examined downstream signaling targets to study the BMP–Smad and BMP–p38 mitogen-activated protein kinase (MAPK) pathways in FOP.

Materials and Methods: Protein phosphorylation was assayed by immunoblots, and p38 MAPK activity was measured by kinase assays. To examine BMP target genes, the mRNA expression of ID1, ID3, and MSX2 was determined by quantitative real-time PCR. Statistical analysis was performed using Student's t-test or ANOVA.

Results: FOP lymphocytes exhibited increased levels of p38 phosphorylation and p38 MAPK activity in response to BMP4 stimulation. Furthermore, in response to BMP4, FOP cells overexpressed the downstream signaling targets ID1 by 5-fold and ID3 by 3-fold compared with controls. ID1 and ID3 mRNA induction was specifically blocked with a p38 MAPK inhibitor, but not extracellular signal-related kinase (ERK) or c-Jun N-terminal kinase (JNK) inhibitors. MSX2, a known Smad pathway target gene, is not upregulated in control or FOP cells in response to BMP, suggesting that lymphocytes do not use this limb of the BMP pathway. However, introduction of Smad1 into lymphocytes made the cells competent to regulate MSX2 mRNA after BMP4 treatment.

Conclusions: Lymphocytes are a cell system that signals primarily through the BMP–p38 MAPK pathway rather than the BMP–Smad pathway in response to BMP4. The p38 MAPK pathway is dysregulated in FOP lymphocytes, which may play a role in the pathogenesis of FOP.
Impact of Recent Fracture on Health-Related Quality of Life in Postmenopausal Women
Authors: Brenneman Susan K , Barrett-Connor Elizabeth , Sajjan Shiva , Markson Leona E , Siris Ethel S
Published: June 2006

The effect of fractures other than hip and spine on HRQoL in younger and older women has not been extensively studied. In a cohort of 86,128 postmenopausal women, we found the impact of recent osteoporosis-related fractures on HRQoL to be similar between women <65 compared with those ≥65 years of age. The impact of spine, hip, or rib fractures was greater than that of wrist fractures in both age groups.

Introduction: Health-related quality of life (HRQoL) after vertebral and hip fractures has been well studied. Less is known about HRQoL after fractures at other sites. We studied the effect of recent clinical fractures on HRQoL, using Short Form-12 (SF-12).

Materials and Methods: This study included 86,128 postmenopausal participants in the National Osteoporosis Risk Assessment (NORA) who responded to two follow-up surveys during a 2-year interval. At each survey, they completed the SF-12 HRQoL questionnaire and reported new fractures of the hip, spine, wrist, and rib. The effect of recent fracture on HRQoL was assessed by comparing Physical Component Score (PCS) and Mental Component Score (MCS) means for women with and without new fractures at the second survey. Analyses were by fracture type and by age group (50–64 and 65–99) and were adjusted for PCS and MCS at the first survey.

Results: New fractures (320 hip, 445 vertebral, 657 rib, 835 wrist) occurring during the interval between the first and second follow-up surveys were reported by 2257 women. The PCS was poorer in both older and younger women who had fractured the hip, spine, or rib (p ≤ 0.001). Wrist fractures had an impact on PCS in women ≤65 years of age (p < 0.001), but not older women (p > 0.10). These differences in PCS by fracture status were similar to those reported for other chronic diseases such as asthma, chronic obstructive pulmonary disease (COPD), and osteoarthritis. MCS was less consistently changed by fracture status, but younger and older women with vertebral fracture (p < 0.004), older women with hip fracture (p < 0.004), and younger women with rib fracture (p < 0.004) had poorer MCS compared with those who did not fracture within their age cohort.

Conclusions: Recent osteoporosis-related fractures have significant impact on HRQoL as measured by SF-12. The impact of recent fracture on HRQoL was similar for older and younger postmenopausal women. Fracture prevention and postfracture interventions that target the subsequent symptoms are needed for postmenopausal women of any age.
A Positive Dose–Response Effect of Vitamin D Supplementation on Site-Specific Bone Mineral Augmentation in Adolescent Girls: A Double-Blinded Randomized Placebo-Controlled 1-Year Intervention
Authors: Viljakainen Heli T , Natri Anna-Mari , Kärkkäinen Merja , Huttunen Minna M , Palssa Anette , Jakobsen Jette , Cashman Kevin D , Mølgaard Christian , Lamberg-Allardt Christel
Published: June 2006

The effect of vitamin D supplementation on bone mineral augmentation in 212 adolescent girls with adequate calcium intake was studied in a randomized placebo-controlled setting. Bone mineral augmentation determined by DXA increased with supplementation both in the femur and the lumbar vertebrae in a dose-responsive manner. Supplementation decreased the urinary excretion of resorption markers, but had no impact on formation markers.

Introduction: Adequate vitamin D intake protects the elderly against osteoporosis, but there exists no indisputable evidence that vitamin D supplementation would benefit bone mineral augmentation. The aim of this 1-year study was to determine in a randomized double-blinded trial the effect of 5 and 10 μg vitamin D3 supplementation on bone mineral augmentation in adolescent girls with adequate dietary calcium intake.

Materials and Methods: Altogether, 228 girls (mean age, 11.4 ± 0.4 years) participated. Their BMC was measured by DXA from the femur and lumbar spine. Serum 25-hydroxyvitamin D [S-25(OH)D], intact PTH (S-iPTH), osteocalcin (S-OC), and urinary pyridinoline (U-Pyr) and deoxypyridinoline (U-Dpyr) were measured. Statistical analysis was performed both with the intention-to-treat (IT) and compliance-based (CB) method.

Results: In the CB analysis, vitamin D supplementation increased femoral BMC augmentation by 14.3% with 5 μg and by 17.2% with 10 μg compared with the placebo group (ANCOVA, p = 0.012). A dose–response effect was observed in the vertebrae (ANCOVA, p = 0.039), although only with the highest dose. The mean concentration of S-25(OH)D increased (p < 0.001) in the 5-μg group by 5.7 ± 15.7 nM and in the 10-μg group by 12.4 ± 13.7 nM, whereas it decreased by 6.7 ± 11.3 nM in the placebo group. Supplementation had no effect on S-iPTH or S-OC, but it decreased U-DPyr (p = 0.042).

Conclusions: Bone mineral augmentation in the femur was 14.3% and 17.2% higher in the groups receiving 5 and 10 μg of vitamin D, respectively, compared with the placebo group, but only 10 μg increased lumbar spine BMC augmentation significantly. Vitamin D supplementation decreased the concentration of bone resorption markers, but had no impact on bone formation markers, thus explaining increased bone mineral augmentation. However, the positive effects were noted with the CB method but not with IT.
HES1 Cooperates With pRb to Activate RUNX2-Dependent Transcription
Authors: Lee Jong-Seo , Thomas David M , Gutierrez Gabriel , Carty Shannon A , Yanagawa Shin-ichi , Hinds Philip W
Published: June 2006

The retinoblastoma protein, pRb, can activate the transcription factor RUNX2, an essential regulator of osteogenic differentiation, but the mechanism of this activation is unknown. Here we studied the interaction of pRb and RUNX2 with HES1, previously reported to augment RUNX2 activity. PRb can act to promote RUNX2/HES1 association with concomitant promoter occupancy and transcriptional activation in bone cells.

Introduction: RUNX2 (also known as OSF2/CBFA1) is a transcription factor required for osteoblast differentiation and bone formation. We have reported that RUNX2 can associate with the retinoblastoma protein pRb, a common tumor suppressor in bone, and the resultant complex can bind and activate transcription from bone-specific promoters. This activity of the pRb/RUNX2 complex may thus link differentiation control with tumor suppressor activity. However, the mechanism through which pRb can activate RUNX2 is unknown. HES1 is a reported co-activator of RUNX2 that shares a binding site on RUNX2 with pRb. Thus, we have tested the cooperativity among these factors in activating transcription from bone specific promoters.

Materials and Methods: Coimmunoprecipitation, chromatin immunoprecipitation, and EMSA experiments were used to study the interaction of RUNX2, HES1, and pRb in cell lysates and on DNA. Transcriptional reporter assays were used to analyze the activity of RUNX2 in the presence and absence of HES1 and pRb.

Results: We showed that pRb can associate with HES1, a previously described RUNX2 interactor that can itself augment RUNX2-dependent transcription. The association of HES1 with RUNX2 is augmented by pRb. Furthermore, both pRb and HES1 increase the amount of RUNX2 bound to promoter sites in vivo, pRb and HES1 synergistically activate a RUNX2-dependent reporter gene, and depletion of HES1 reduces RUNX2/pRb activity.

Conclusions: These data indicate that pRb acts as a RUNX2 co-activator at least in part by recruiting HES1 into the pRb/RUNX2 complex and further elucidate a novel role for pRb as a transcriptional co-activator in osteogenesis.
BMP-2 Gene Polymorphisms and Osteoporosis: The Rotterdam Study
Authors: Medici Marco , van Meurs Joyce BJ , Rivadeneira Fernando , Zhao HongYan , Arp Pascal P , Hofman Albert , Pols Huibert AP , Uitterlinden André G
Published: June 2006

After reported associations of variations in the BMP-2 gene with osteoporosis in small populations, we studied the association of the BMP-2 gene polymorphisms Ser37Ala and Arg190Ser with osteoporosis in 6353 men and women from the Rotterdam Study. We did not observe an association of these variants with BMD, bone loss, hip structural analysis parameters, and fracture risk.

Introduction: Bone morphogenetic protein 2 (BMP-2) plays a role in osteoblast differentiation. BMP-2 gene variation has previously been associated with osteoporosis in various small populations, but current evidence remains inconclusive about the exact association with osteoporosis. Therefore, we studied the association of two polymorphisms located in the BMP-2 gene (Ser37Ala and Arg190Ser) and haplotypes defined by these polymorphisms with BMD, rates of bone loss, parameters of hip structural analysis (HSA), and fractures in the Rotterdam Study, a large prospective cohort study of diseases in the elderly.

Materials and Methods: Databases were searched for polymorphisms and haplotype blocks in the BMP-2 gene region. Allele frequencies for Ser37Ala and Arg190Ser were determined in 60 blacks and 110 Chinese from Coriell panels. Genotype data on Ser37Ala and Arg190Ser were available for 6353 individuals from the Rotterdam Study population. Haplotype alleles defined by Ser37Ala and Arg190Ser were inferred using PHASE software. Genotype and haplotype analyses for BMD (measured at the lumbar spine and femoral neck), bone loss per year (measured at the femoral neck), and HSA were performed using AN(C)OVA. Fractures were analyzed using a Cox proportional-hazards model and logistic regression. All outcomes were adjusted for age, height, and weight.

Results: Allele frequencies were 2.5% for Ala37 and 40.2% for Ser190, whereas haplotype allele frequencies were 57.28% (Ser37Arg190), 40.19% (Ser37Ser190), 2.50% (Ala37Arg190), and 0.02% (Ala37Ser190). For BMD, bone loss, HSA outcomes, and (incident) fractures, no differences could be seen between genotype and haplotype groups.

Conclusions: In this large population-based cohort of Dutch whites, we conclude that the BMP-2 Ser37Ala and Arg190Ser polymorphisms or haplotypes thereof are not associated with parameters of osteoporosis.
Fibroblast Growth Factor-2 Is an Immediate-Early Gene Induced by Mechanical Stress in Osteogenic Cells
Authors: Li Chai-Fei , Hughes-Fulford Millie
Published: June 2006

Fifteen minutes of physiological MS induces FGF-2 in osteogenic cells. Here, we show that MS induced proliferation in both MC3T3-E1 and BMOp cells isolated from Fgf2+/+ mice; Fgf2−/− BMOp cells required exogenous FGF-2 for a normal proliferation response. The induction of fgf-2 is mediated by PKA and ERK pathways.

Introduction: Mechanical stress (MS) induces gene expression and proliferation of osteogenic MC3T3-E1 cells. We have previously shown that physiological levels of MS in MC3T3-E1 cells causes extracellular signal–regulated kinase (ERK)1/2 phosphorylation. Here we evaluate the induction and importance of fibroblast growth factor-2 (FGF-2) for MS-induced proliferation.

Materials and Methods: We characterized the MS induction of fgf-2 using a 15-minute pulse of 120 μstrain and studied the stability of fgf-2 message using actinomycin D. Bone marrow stromal cells (BMOp) isolated from Fgf2−/− and Fgf2+/+ mice were used to study the importance of FGF-2 in MS-induced proliferation.

Results: We found that the induction of fgf-2 by MS is dependent on both protein kinase A (PKA) and ERK pathways. MS transiently induces fgf-2 within 30 minutes. FGF-2 receptor (FGFR2) was also significantly increased within 1 h. All three isoforms of FGF-2 (24, 22, and 18 kDa) were significantly increased by MS. The MS-mediated increase of fgf-2 mRNA was caused by new synthesis and not stabilization. Pretreatment of MC3T3-E1 cells with cycloheximide showed that the induction of fgf-2 did not require new protein synthesis. Pretreating MC3T3-E1 cells with the mitogen-activated protein kinase (MAPK)/ERK kinase 1/2 (MEK1/2) inhibitor, U0126, or H-89, a PKA inhibitor, significantly inhibited the induction of fgf-2, showing that mechanical induction of fgf-2 is dependent on ERK and PKA signaling pathways. The downstream consequence of a single 15-minute stress pulse was a 3.5-fold increase in cell number in MC3T3-E1 compared with growth in nonstressed control cells. In studies using bone marrow osteoprogenitor cells (BMOp) isolated from Fgf2+/+and Fgf2−/− mice, we found that FGF-2 was necessary for a full proliferative response to MS.

Conclusions: These studies show that FGF-2 is an immediate-early gene induced by MS, and its expression is mediated by both the PKA and MAPK signal transduction pathways. FGF-2 was required for a full proliferative response.
Transgenic Mice Overexpressing Macrophage Migration Inhibitory Factor (MIF) Exhibit High-Turnover Osteoporosis
Authors: Onodera Shin , Sasaki Satoshi , Ohshima Shigeki , Amizuka Norio , Li Minqi , Udagawa Nobuyuki , Irie Kazuharu , Nishihira Jun , Koyama Yoshikazu , Shiraishi Ayako , Tohyama Harukazu , Yasuda Kazunori
Published: June 2006

The bone phenotype of mice overexpressing MIF was studied. These mice showed decreased trabecular bone, increased bone formation rate, and increased MMP-3, −9, and −13 mRNA expression in the femora and tibias. This model provides evidence of the role played by MIF in bone remodeling and balance in vivo.

Introduction: The role of macrophage migration inhibitory factor (MIF) in in vivo bone remodeling remains unelucidated. We describe disordered bone metabolism in transgenic mice overexpressing MIF.

Materials and Methods: For in vivo study, μCT, bone histomorphometry, blood and urine biochemical data, and gene expression of MIF transgenic (MIF Tg) mice and littermate wildtype (WT) mice were examined. For in vitro study, osteoclastogenesis in the co-culture of bone marrow cells and osteoblasts from MIF Tg and WT were assessed.

Results: μCT analyses revealed a significant reduction in the trabecular bone of distal femur in MIF Tg at 8–12 weeks of age. Histomorphometric analysis revealed increase in several measures of bone formation. Osteoclastogenesis was not influenced by the origin of bone marrow cells or osteoblasts. Urine level of deoxypyridinoline/creatinine and the mRNA levels of matrix metalloproteinase (MMP) −3, −9, and −13 in femurs were elevated in MIF Tg.

Conclusions: Overexpression of MIF causes high-turnover osteoporosis in mice. The increased expression of MMPs in bone was suggested, at least in part, as one cause of this phenotype, because MMPs plays important roles for bone resorption without affecting the formation of osteoclasts. This model provides evidence of the role played by MIF in bone remodeling and balance.
Teriparatide Increases Bone Formation in Modeling and Remodeling Osteons and Enhances IGF-II Immunoreactivity in Postmenopausal Women With Osteoporosis
Authors: Ma Yanfei L , Zeng Qingqiang , Donley David W , Ste-Marie Louis-Georges , Gallagher J Christopher , Dalsky Gail P , Marcus Robert , Eriksen Erik Fink
Published: June 2006

Transiliac bone biopsies were obtained from 55 women treated with teriparatide or placebo for 12–24 months. We report direct evidence that modeling bone formation at quiescent surfaces was present only in teriparatide-treated patients and bone formation at remodeling sites was higher with teriparatide than placebo.

Introduction: Recombinant teriparatide [human PTH(1-34)], a bone formation agent for the treatment of osteoporosis when given once daily subcutaneously, increases biochemical markers of bone turnover and activation frequency in histomorphometry studies.

Materials and Methods: We studied the mechanisms underlying this bone-forming action of teriparatide at the basic multicellular unit by the appearance of cement lines, a method used to directly classify surfaces as modeling or remodeling osteons, and by the immunolocalization of IGF-I and IGF-II. Transiliac bone biopsies were obtained from 55 postmenopausal women treated with teriparatide 20 or 40 μg or placebo for 12–24 months (median, 19.8 months) in the Fracture Prevention Trial.

Results: A dose-dependent relationship was observed in modeling and mixed remodeling/modeling trabecular hemiosteons. Trabecular and endosteal hemiosteon mean wall thicknesses were significantly higher in both teriparatide groups than in placebo. There was a dose-dependent relationship in IGF-II immunoreactive staining at all bone envelopes studied. The greater local IGF-II presence after treatment with teriparatide may play a key role in stimulating bone formation.

Conclusions: Direct evidence is presented that 12–24 months of teriparatide treatment induced modeling bone formation at quiescent surfaces and resulted in greater bone formation at remodeling sites, relative to placebo.
Function and Regulation of Osteopontin in Response to Mechanical Stress
Authors: Fujihara Shinji , Yokozeki Masahiko , Oba Yasuo , Higashibata Yuji , Nomura Shintaro , Moriyama Keiji
Published: June 2006

Extensive histological study revealed the impairment of bone remodeling caused by mechanical stress in OPN knockout mice in a tooth movement system. Analysis of OPN promoter transgenic mice showed the mechanical stress response element(s) in the 5.5-kb upstream region. These results were also obtained with the primary cultured cells.

Introduction: Mechanical loading system changes the bone architecture through the stimulation of bone remodeling by the action of a numbers of molecules. Among them, we showed that osteopontin (OPN) plays an important role in response to mechanical loading in rats with an experimental system for tooth movement. The results indicate the important role of OPN in bone remodeling. However, the molecular mechanism of OPN expression in response to mechanical stress is unknown.

Materials and Methods: OPN knockout mice and transgenic mice carrying green fluorescent protein (GFP) in the control of the OPN promoter were used for analysis. Orthodontic closed coil springs were bonded to the maxillary first molars and incisors for the experimental tooth movement. Spatial expression of GFP and OPN was detected by in situ hybridization.

Results: In contrast to wildtype mice, a smaller number of TRACP+ cells was detected in OPN knockout mice after treatment. In GFP-OPN5.5 mice, OPN and GFP mRNA-expressing cells were detected in bone cells after treatment, and the localization of GFP was consistent with that of endogenous OPN. An increase in the co-expression of GFP and OPN was detected when primary cultured osteoblastic cells derived from the transgenic mice were exposed to strain or pressure force. Significant increase in the number of OPN+ osteocyte was detected in the pressure side at 48 h after treatment. At 72 h, increase in the number of TRACP+ cells was detected predominantly in the pressure side.

Conclusions: Bone remodeling in response to mechanical stress was suppressed in OPN knockout mice. These results indicate the critical role of OPN in the process of bone remodeling. The analysis of GFP expression in the promoter transgenic mice indicated the presence of an in vivo mechanical stress response element in the 5.5-kb upstream region of the OPN gene.
"Sister Souls": Bernard Berenson and Michael Field (Katherine Bradley and Edith Cooper)
Authors: VICINUS MARTHA
Published: June 2006

In the 1890s the poet Michael Field-the lesbian aunt-and-niece couple, Katharine Bradley (1846 -1914) and Edith Cooper (1862-1913)-were close friends with the art connoisseur Bernard Berenson (1865-1959). Under the influence of Walter Pater,the three avidly discussed the connections uniting the artwork, viewer, and artist. Critics have long known that Cooper fell passionately in love with Berenson, but no one has examined this relationship closely. This essay uses the Michael Field poems, letters, and diaries to explore the impact of falling in love with a man on the Bradly-Cooper relationship and their poetry. Cooper felt that she and Berenson were faun-like creatures who instinctively understood each other on a deeper level than the physical. Berenson sought Cooper's ethereal independence while he was courting a married woman;Cooper turned to him when she wanted a more separate life from her aunt. Berenson never forgot Cooper's intense emotional response to visual art, a response that represented his aesthetic ideal. Cooper experienced a burst of creativity, reliving her intoxicating love in verse and prose. Bradley, as the older woman, struggled to reconcile herself to this attractive, destructive male intrusion into Michael Field's poetic and personal "oneness." The three drew on the emotions that they stirred in each other as a source of inspiration, but each discovered that emotion can outrun aesthetics.
Plato, Aesop, and the Beginnings of Mimetic Prose
Authors: KURKE LESLIE
Published: June 2006

ABSTRACT This paper traces out the lineaments of a popular Aesop tradition behind and within Plato's characterization of Socrates in his dialogues. It attempts thereby to expose the mimetic origins of philosophic prose writing (at least partly) in the lowly and abjected fabular discourse of Aesop, which Platonic dialogue strategically appropriates and disavows to constitute “philosophy” as an autonomous, transcendent domain of inquiry.
Forensic Aspects of Renaissance Mimesis
Authors: HUTSON LORNA
Published: June 2006

ABSTRACT Current approaches to Renaissance drama, rejecting the older idea of mimesis as likeness to an essential “nature,” have also rejected the assumption that Shakespeare's drama is especially mimetic. This article argues that these approaches neglect the contribution of narrative coherence or plot tomimesis and shows that a judicial conception of narrative underlies the mimesis of neoclassical Renaissance drama, including Shakespeare. Mimetic readings of Shakespeare may thus be appropriately legalistic responses to an evidentially based conception of plot.
A Nonself Recognition Gene Complex inNeurospora crassa
Authors: Micali Cristina O , Smith Myron L
Published: June 2006

Nonself recognition is exemplified in the fungal kingdom by the regulation of cell fusion events between genetically different individuals (heterokaryosis). The het-6 locus is one of ∼10 loci that control heterokaryon incompatibility during vegetative growth of N. crassa. Previously, it was found that het-6-associated incompatibility in Oak Ridge (OR) strains involves two contiguous genes, het-6 and un-24. The OR allele of either gene causes “strong” incompatibility (cell death) when transformed into Panama (PA)-background strains. Several remarkable features of the locus include the nature of these incompatibility genes (het-6 is a member of a repetitive gene family and un-24 also encodes the large subunit of ribonucleotide reductase) and the observation that un-24 and het-6 are in severe linkage disequilibrium. Here, we identify “weak” (slow, aberrant growth) incompatibility activities by un-24PA and het-6PA when transformed separately into OR strains, whereas together they exhibit an additive, strong effect. We synthesized strains with the new allelic combinations un-24PA  het-6OR and un-24OR  het-6PA, which are not found in nature. These strains grow normally and have distinct nonself recognition capabilities but may have reduced fitness. Comparing the Oak Ridge and Panama het-6 regions revealed a paracentric inversion, the architecture of which provides insights into the evolution of the un-24–het-6 gene complex.
ELM1 Is Required for Multidrug Resistance in Saccharomyces cerevisiae
Authors: Souid Abdul-Kader , Gao Chen , Wang Luming , Milgrom Elena , Shen W-C Winston
Published: June 2006

In Saccharomyces cerevisiae, transcription of several drug transporter genes, including the major transporter gene PDR5, has been shown to peak during mitosis. The significance of this observation, however, remains unclear. PDR1 encodes the primary transcription activator of multiple drug transporter genes in S. cerevisiae, including PDR5. Here, we show that in synchronized PDR1 and pdr1-3 (multidrug resistant) strains, cellular efflux of a known substrate of ATP-binding-cassette transporters, doxorubicin (a fluorescent anticancer drug), is highest during mitosis when PDR5 transcription peaks. A genetic screen performed to identify regulators of multidrug resistance revealed that a truncation mutation in ELM1 (elm1-300) suppressed the multidrug resistance of pdr1-3. ELM1 encodes a serine/threonine protein kinase required for proper regulation of multiple cellular kinases, including those involved in mitosis, cytokinesis, and cellular morphogenesis. elm1-300 as well as elm1Δ mutations in a pdr1-3 strain also caused elongated bud morphology (indicating a G2/M delay) and reduction of PDR5 transcription under induced and noninduced conditions. Interestingly, mutations in several genes functionally related to ELM1, including cla4Δ, gin4Δ, and cdc28-C127Y, also caused drastic reductions in drug resistance and PDR5 transcription. Collectively, these data show that ELM1, and genes encoding related serine/threonine protein kinases, are required for regulation of multidrug resistance involving, at least in part, control of PDR5 transcription.
Simultaneous Fine Mapping of Multiple Closely Linked Quantitative Trait Loci Using Combined Linkage Disequilibrium and Linkage With a General Pedigree
Authors: Lee S H , Van der Werf J H J
Published: June 2006

Within a small region (e.g., <10 cM), there can be multiple quantitative trait loci (QTL) underlying phenotypes of a trait. Simultaneous fine mapping of closely linked QTL needs an efficient tool to remove confounded shade effects among QTL within such a small region. We propose a variance component method using combined linkage disequilibrium (LD) and linkage information and a reversible jump Markov chain Monte Carlo (MCMC) sampling for model selection. QTL identity-by-descent (IBD) coefficients between individuals are estimated by a hybrid MCMC combining the random walk and the meiosis Gibbs sampler. These coefficients are used in a mixed linear model and an empirical Bayesian procedure combines residual maximum likelihood (REML) to estimate QTL effects and a reversible jump MCMC that samples the number of QTL and the posterior QTL intensities across the tested region. Note that two MCMC processes are used, i.e., an (internal) MCMC for IBD estimation and an (external) MCMC for model selection. In a simulation study, the use of the multiple-QTL model clearly removes the shade effects between three closely linked QTL located at 1.125, 3.875, and 7.875 cM across the region of 10 cM, using 40 markers at 0.25-cM intervals. It is shown that the use of combined LD and linkage information gives much more useful information compared to using linkage information alone for both single- and multiple-QTL analyses. When using a lower marker density (11 markers at 1-cM intervals), the signal of the second QTL can disappear. Extreme values of past effective size (resulting in extreme levels of LD) decrease the mapping accuracy.
The F-Box Protein Dia2 Overcomes Replication Impedance to Promote Genome Stability in Saccharomyces cerevisiae
Authors: Blake Deborah , Luke Brian , Kanellis Pamela , Jorgensen Paul , Goh Theo , Penfold Sonya , Breitkreutz Bobby-Joe , Durocher Daniel , Peter Matthias , Tyers Mike
Published: June 2006

The maintenance of DNA replication fork stability under conditions of DNA damage and at natural replication pause sites is essential for genome stability. Here, we describe a novel role for the F-box protein Dia2 in promoting genome stability in the budding yeast Saccharomyces cerevisiae. Like most other F-box proteins, Dia2 forms a Skp1-Cdc53/Cullin-F-box (SCF) E3 ubiquitin–ligase complex. Systematic analysis of genetic interactions between dia2Δ and ∼4400 viable gene deletion mutants revealed synthetic lethal/synthetic sick interactions with a broad spectrum of DNA replication, recombination, checkpoint, and chromatin-remodeling pathways. dia2Δ strains exhibit constitutive activation of the checkpoint kinase Rad53 and elevated counts of endogenous DNA repair foci and are unable to overcome MMS-induced replicative stress. Notably, dia2Δ strains display a high rate of gross chromosomal rearrangements (GCRs) that involve the rDNA locus and an increase in extrachromosomal rDNA circle (ERC) formation, consistent with an observed enrichment of Dia2 in the nucleolus. These results suggest that Dia2 is essential for stable passage of replication forks through regions of damaged DNA and natural fragile regions, particularly the replication fork barrier (RFB) of rDNA repeat loci. We propose that the SCFDia2 ubiquitin ligase serves to modify or degrade protein substrates that would otherwise impede the replication fork in problematic regions of the genome.
Spatial and Temporal Divergence of Expression in Duplicated Barley Germin-Like Protein-Encoding Genes
Authors: Federico Maria L , Iñiguez-Luy Federico L , Skadsen Ronald W , Kaeppler Heidi F
Published: June 2006

Subfunctionalization is the process by which a pair of duplicated genes, or paralogs, experiences a reduction of individual expression patterns or function while still reproducing the complete expression pattern and function of the ancestral gene. Two germin-like protein (GLP)-encoding genes, GerB and GerF, are paralogs that belong to a small gene family in barley (Hordeum vulgare). Both genes share high nucleotide sequence similarity in coding and noncoding regions and encode identical apoplastic proteins. The use of RNA gel blots, coupled with single-stranded conformation polymorphism (SSCP) analysis of RT–PCR products, elucidated the developmental and tissue-specific expression patterns of each gene. Individual expression patterns provided evidence of both overlapping redundancy and early subfunctionalization. GerB is predominantly expressed in developing shoots, while GerF is predominantly expressed in seedling roots, developing spikes, and pericarp/testa. GerF promoter deletion studies located a region (−356/−97) responsible for high promoter activity and showed the ability of GerB and GerF upstream regions to drive gfp expression in coleoptiles, epicarps, and lemma/palea of developing spikes. The observed expression patterns are consistent with proposed roles in plant development and defense mechanisms for this gene family. These roles may explain why redundancy has been selectively maintained in this duplicate gene pair.
Long-Term Evolution and Functional Diversification in the Members of the Nucleophosmin/Nucleoplasmin Family of Nuclear Chaperones
Authors: Eirín-López José M , Frehlick Lindsay J , Ausió Juan
Published: June 2006

The proper assembly of basic proteins with nucleic acids is a reaction that must be facilitated to prevent protein aggregation and formation of nonspecific nucleoprotein complexes. The proteins that mediate this orderly protein assembly are generally termed molecular (or nuclear) chaperones. The nucleophosmin/nucleoplasmin (NPM) family of molecular chaperones encompasses members ubiquitously expressed in many somatic tissues (NPM1 and -3) or specific to oocytes and eggs (NPM2). The study of this family of molecular chaperones has experienced a renewed interest in the past few years. However, there is a lack of information regarding the molecular evolution of these proteins. This work represents the first attempt to characterize the long-term evolution followed by the members of this family. Our analysis shows that there is extensive silent divergence at the nucleotide level suggesting that this family has been subject to strong purifying selection at the protein level. In contrast to NPM1 and NPM-like proteins in invertebrates, NPM2 and NPM3 have a polyphyletic origin. Furthermore, the presence of selection for high frequencies of acidic residues as well as the existence of higher levels of codon bias was detected at the C-terminal ends, which can be ascribed to the critical role played by these residues in constituting the acidic tracts and to the preferred codon usage for phosphorylatable amino acids at these regions.