bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysosteosclerosis presents as an “Osteoclast-Poor” form of osteopetrosis: Comprehensive investigation of a 3-year-old girl and literature review
Authors: Whyte Michael P , Wenkert Deborah , McAlister William H , Novack Deborah V , Nenninger Angie R , Zhang Xiafang , Huskey Margaret , Mumm Steven 
Published: May 2010

Abstract
Dysosteosclerosis (DSS), an extremely rare dense bone disease, features short stature and fractures and sometimes optic atrophy, cranial nerve palsy, developmental delay, and failure of tooth eruption in infancy or early childhood consistent with osteopetrosis (OPT). Bone histology during childhood shows unresorbed primary spongiosa from deficient osteoclast action. Additionally, there is remarkable progressive flattening of all vertebrae and, by adolescence, paradoxical metaphyseal osteopenia with thin cortical bone. Reports of consanguinity indicate autosomal recessive inheritance, yet more affected males than females suggest X-linked recessive inheritance. We investigated a nonconsanguineous girl with DSS. Osteosclerosis was discovered at age 7 months. Our studies, spanning ages 11 to 44 months, showed weight at approximately 50th percentile, and length diminishing from approximately 30th percentile to –2.3 SD. Head circumference was +4 SD. The patient had frontal bossing, blue sclera, normal teeth, genu valgum, and unremarkable joints. Radiographs showed orbital and facial sclerosis, basilar thickening, bone-in-bone appearance of the pelvis, sclerotic long bone ends, and fractures of ribs and extremities. Progressive metaphyseal widening occurred as vertebrae changed from ovoid to flattened and became beaked anteriorly. A hemogram was normal. Consistent with OPT, serum parathyroid hormone (PTH) concentrations reflected dietary calcium levels. Serum bone alkaline phosphatase, osteocalcin, and TRACP-5b were subnormal. The iliac crest contained excessive primary spongiosa and no osteoclasts. No mutations were identified in the splice sites or exons for the genes encoding chloride channel 7, T-cell immune regulator 1, OPT-associated transmembrane protein 1, and monocyte colony-stimulating factor (M-CSF) and its receptor C-FMS, ANKH, OPG, RANK, and RANKL. Genomic copy-number microarray was unrevealing. Hence, DSS is a distinctive OPT of unknown etiology featuring osteoclast deficiency during early childhood. How osteopenia follows is an enigma of human skeletal pathobiology. © 2010 American Society for Bone and Mineral Research.
Mutations of SQSTM1 are associated with severity and clinical outcome in paget disease of bone
Authors: Visconti Micaela Rios , Langston Anne L , Alonso Nerea , Goodman Kirsteen , Selby Peter L , Fraser William D , Ralston Stuart H 
Published: May 2010

Abstract
Paget disease of bone (PDB) is a common disorder characterized by increased bone turnover at one of more sites throughout the skeleton. Genetic factors play an important role in the pathogenesis of PDB, and the most important predisposing gene is SQSTM1, which is mutated in about 10% of patients. Here we investigated the relationship between SQSTM1 mutation status, disease severity, and clinical outcome in 737 patients who took part in a randomized study of two different management strategies for the disease. Mutations of SQSTM1 were detected in 80 of 737 (10.9%) patients. Mutation carriers had an earlier age at diagnosis (59.4 ±11.5 versus 65.0 ± 10.4 years, p &lt; .0001) and a greater number of affected bones (3.2 ± 1.2 versus 2.1 ± 1.2, p &lt; .001) and more commonly required orthopedic surgery (26.2% versus 16.1%, p = .024) and bisphosphonate therapy (86.3% versus 75.2%, p = .01) than those without mutations. Quality of life, as assessed by the short-form-36 (SF36) physical summary score, was significantly reduced in carriers (34.0 ± 11.3 versus 37.1 ± 11.4, p = .036). During the study, fractures were more common in carriers (12.5% versus 5.3%, p = .011), although most of these occurred in unaffected bone. This study demonstrates that SQSTM1 mutations are strongly associated with disease severity and complications of PDB. Genetic testing for SQSTM1 mutations may be of value in identifying individuals at risk of developing severe disease, but further studies will be required to determine if a program of genetic testing and early intervention in these individuals would be cost-effective or be of benefit in preventing these complications. © 2010 American Society for Bone and Mineral Research.
Adverse interaction of low-calcium diet and low 25(OH)D levels on lumbar spine mineralization in late-pubertal girls
Authors: Esterle Laure , Nguyen Minh , Walrant-Debray Odile , Sabatier Jean-Pierre , Garabedian Michèle 
Published: May 2010

Abstract
No consensus has been reached on the serum 25-hydroxyvitamin D [25(OH)D] levels required to ensure optimal bone health around menarche. We searched for a possible interaction of 25(OH)D levels and calcium intake on lumbar spine mineralization and on biologic features of bone metabolism in healthy late-pubertal girls. Lumbar spine parameters (ie, area, mineral content, and density) and calcium intake were evaluated in 211 healthy white adolescent girls at pubertal stages IV–V (11 to 16.9 years), together with biologic markers of calcium and bone metabolism and with International External Quality Assessment Scheme for Vitamin D Metabolite (DEQAS)–validated serum 25(OH)D levels. A high prevalence of 25(OH)D levels ≤ 30 nmol/L (41%), ≤40 nmol/L (61%), and ≤50 nmol/L (70%) was found during winter–spring. Parathyroid hormone (PTH) levels were inversely associated with 25(OH)D levels (p = .0021). In contrast, lumbar spine mineral content and density were not associated with 25(OH)D, excepted when calcium intake was below 600 mg/day (p = .0081). Girls with such low calcium intake and 25(OH)D levels of 40 nmol/L or less (9% of the cohort) had a 0.4 to 0.7 SD lower mean areal bone mineral density Z-score than girls with higher calcium intake and/or higher 25(OH)D status. The adverse association between lumbar spine mineralization and combined calcium deficiency–low 25(OH)D levels remained significant in the 91 girls who could be followed over 4 years after their initial evaluation. We conclude that low 25(OH)D levels (≤40 nmol/L) are observed frequently during winter–spring in late-pubertal European girls, which may exacerbate the negative impact of calcium deficiency on lumbar spine mineralization. © 2010 American Society for Bone and Mineral Research.
Sclerostin antibody treatment enhances metaphyseal bone healing in rats
Authors: Agholme Fredrik , Li Xiaodong , Isaksson Hanna , Ke Hua Zhu , Aspenberg Per 
Published: May 2010

Abstract
Sclerostin is the product of the SOST gene. Loss-of-function mutations in the SOST gene result in a high-bone-mass phenotype, demonstrating that sclerostin is a negative regulator of bone mass. Primarily expressed by osteocytes in bone, sclerostin is reported to bind the LRP5/6 receptor, thereby antagonizing canonical Wnt signaling and negatively regulating bone formation. We therefore investigated whether systemic administration of a sclerostin-neutralizing antibody would increase the regeneration of traumatized metaphyseal bone in rats. Young male rats had a screw inserted in the proximal tibia and were divided into six groups given 25 mg/kg of sclerostin antibody or control twice a week subcutaneously for 2 or 4 weeks. In four groups, the screws were tested for pull-out strength. At the time of euthanasia, a similar screw also was inserted in the contralateral tibia and pull-out tested immediately. Sclerostin antibody significantly increased the pull-out force by almost 50% compared with controls after 2 and 4 weeks. Also, the screws inserted at the time of euthanasia showed increased pull-out force. Micro–computed tomography (µCT) of the remaining two groups showed that the antibody led to a 30% increase in bone volume fraction in a region surrounding the screw. There also was a general increase in trabecular thickness in cancellous bone. Thus, as measured by the amount of bone and its mechanical resistance, the sclerostin antibody increased bone formation during metaphyseal repair but also in untraumatized bone. © 2010 American Society for Bone and Mineral Research.
Identification of a gene module associated with BMD through the integration of network analysis and genome-wide association data
Authors: Farber Charles R 
Published: May 2010

AbstractBone mineral density (BMD) is influenced by a complex network of gene interactions; therefore, elucidating the relationships between genes and how those genes, in turn, influence BMD is critical for developing a comprehensive understanding of osteoporosis. To investigate the role of transcriptional networks in the regulation of BMD, we performed a weighted gene coexpression network analysis (WGCNA) using microarray expression data on monocytes from young individuals with low or high BMD. WGCNA groups genes into modules based on patterns of gene coexpression. and our analysis identified 11 gene modules. We observed that the overall expression of one module (referred to as module 9) was significantly higher in the low-BMD group (p = .03). Module 9 was highly enriched for genes belonging to the immune system–related gene ontology (GO) category “response to virus” (p = 7.6 × 10−11). Using publically available genome-wide association study data, we independently validated the importance of module 9 by demonstrating that highly connected module 9 hubs were more likely, relative to less highly connected genes, to be genetically associated with BMD. This study highlights the advantages of systems-level analyses to uncover coexpression modules associated with bone mass and suggests that particular monocyte expression patterns may mediate differences in BMD. © 2010 American Society for Bone and Mineral Research.
Inhibition of TGF-β signaling by 1D11 antibody treatment increases bone mass and quality in vivo
Authors: Edwards James R , Nyman Jeffry S , Lwin Seint T , Moore Megan M , Esparza Javier , O'Quinn Elizabeth C , Hart Andrew J , Biswas Swati , Patil Chetan A , Lonning Scott , Mahadevan-Jansen Anita , Mundy Gregory R 
Published: May 2010

Abstract
Transforming growth factor β (TGF-β) is an abundant bone matrix protein that influences osteoblast and osteoclast interactions to control bone remodeling. As such, TGF-β represents an obvious pharmacologic target with the potential to regulate both bone formation and resorption to improve bone volume and strength. To investigate the skeletal effect of TGF-β inhibition in vivo, we used an antibody (1D11) specifically directed at all three isoforms of TGF-β. Normal mice were treated with 1D11 or control antibody (4 weeks), and cortical and trabecular bone was assessed by micro–computed tomographic (µCT) scanning. Bone volume and cellular distribution were determined by histomorphometric analysis of vertebrae and long bones. Also, whole-bone strength was assessed biomechanically by three-point bend testing, and tissue-level modulus and composition were analyzed by nanoindentation and Raman microspectroscopy, respectively. TGF-β blockade by 1D11 increased bone mineral density (BMD), trabecular thickness, and bone volume by up to 54%, accompanied by elevated osteoblast numbers and decreased osteoclasts. Biomechanical properties of bone also were enhanced significantly by 1D11 treatment, with increased bending strength and tissue-level modulus. In addition, Raman microspectroscopy demonstrated that 1D11-mediated TGF-β inhibition in the bone environment led to an 11% increase in the mineral-to-collagen ratio of trabecular bone. Together these studies demonstrate that neutralizing TGF-β with 1D11 increases osteoblast numbers while simultaneously decreasing active osteoclasts in the marrow, resulting in a profound increase in bone volume and quality, similar to that seen in parathyroid hormone (PTH)–treated rodent studies. © 2010 American Society for Bone and Mineral Research.
Time‐dependent quantum study of H(2S) + FO(2Π) → OH(2Π) + F(2P) reaction on the 13A′ and 13A″ states
Authors: Gogtas Fahrettin , Tutuk Rukiye , Kurban Mustafa 
Published: May 2010

AbstractThe dynamics of the H(2S) + FO(2Π) → OH(2Π) + F(2P) reaction on the adiabatic potential energy surface of the 13A′ and 13A″ states is investigated. The initial state selected reaction probabilities for total angular momentum J = 0 have been calculated by using the quantum mechanical real wave packet method. The integral cross sections and initial state selected reaction rate constants have been obtained from the corresponding J = 0 reaction probabilities by means of the simple J‐Shifting technique. The initial state‐selected reaction probabilities and reaction cross section do not manifest any sharp oscillations and the initial state selected reaction rate constants are sensitive to the temperature. © 2010 Wiley Periodicals, Inc. J Comput Chem 2010
Atomic forces for geometry‐dependent point multipole and Gaussian multipole models
Authors: Elking Dennis M. , Perera Lalith , Duke Robert , Darden Thomas , Pedersen Lee G. 
Published: May 2010

AbstractIn standard treatments of atomic multipole models, interaction energies, total molecular forces, and total molecular torques are given for multipolar interactions between rigid molecules. However, if the molecules are assumed to be flexible, two additional multipolar atomic forces arise because of (1) the transfer of torque between neighboring atoms and (2) the dependence of multipole moment on internal geometry (bond lengths, bond angles, etc.) for geometry‐dependent multipole models. In this study, atomic force expressions for geometry‐dependent multipoles are presented for use in simulations of flexible molecules. The atomic forces are derived by first proposing a new general expression for Wigner function derivatives $\partial D_{m'm}^l /\partial \Omega$. The force equations can be applied to electrostatic models based on atomic point multipoles or Gaussian multipole charge density. Hydrogen‐bonded dimers are used to test the intermolecular electrostatic energies and atomic forces calculated by geometry‐dependent multipoles fit to the ab initio electrostatic potential. The electrostatic energies and forces are compared with their reference ab initio values. It is shown that both static and geometry‐dependent multipole models are able to reproduce total molecular forces and torques with respect to ab initio, whereas geometry‐dependent multipoles are needed to reproduce ab initio atomic forces. The expressions for atomic force can be used in simulations of flexible molecules with atomic multipoles. In addition, the results presented in this work should lead to further development of next generation force fields composed of geometry‐dependent multipole models. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010
Docetaxel increases antitumor efficacy of oncolytic prostate‐restricted replicative adenovirus by enhancing cell killing and virus distribution
Authors: Li Xiong , Liu Youhong , Tang Yong , Roger Phipps , Jeng Meei‐Huey , Kao Chinghai 
Published: May 2010

AbstractBackgroundWe explored multiple molecular mechanisms of the combination of docetaxel and an oncolytic prostate‐restricted replication competent adenovirus (Ad) (PRRA) in advanced prostate cancer (PCa) models. The combinational therapy has potential to overcome the therapeutic limitations of poor virus distribution inside solid tumors.MethodsWe evaluated the effect of docetaxel on the antitumor efficacy and efficiency of virus transduction, transgene expression and virus distribution of PRRA in a prostate‐specific antigen/prostate‐specific membrane antigen‐positive tumor xenograft model. We also evaluated the effect of docetaxel on apoptosis induction, cell killing and the efficiency of transgene expression and virus replication in vitro.ResultsTumor growth inhibition was significantly enhanced when docetaxel was administrated before intratumor injection of PRRA. In vivo dual‐photon microscopy and ex vivo fluorescence microscopy and immunohistochemistry showed that docetaxel increased transgene expression and expanded virus distribution. The combination of docetaxel and PRRA also increased cell apoptosis. In vitro, docetaxel significantly increased cell killing in PRRA‐treated PCa cells. Docetaxel significantly increased Ad‐mediated trangene expression independent of Ad binding receptors and replication capability. Docetaxel increased the activity of cytomegalovirus (CMV) promoter but not of a chimeric prostate‐specific enhancer, resulting in higher transgene expression. The enhanced CMV promoter activity resulted from activation of p38 mitogen‐activated protein kinase (MAPK) because inhibition of p38 MAPK blocked the docetaxel‐induced increase in CMV promoter activity.ConclusionsCombining docetaxel with an oncolytic PRRA improved therapeutic potential by expanding virus distribution and enhancing cell apoptosis and killing. These studies suggested a novel mechanism for enhancing the effect of therapeutic genes delivered by a PRRA. Copyright © 2010 John Wiley & Sons, Ltd.
LOCAL GOVERNMENT DISCRETION AND ACCOUNTABILITY IN PHILIPPINES
Authors: Yilmaz Serdar , Venugopal Varsha 
Published: May 2010

AbstractPhilippines has an exhaustive decentralisation code providing local governments with a high degree of discretion. But the concurrent upward and downward accountability mechanisms are weak resulting in inefficiency and ineffectiveness of local governments. We employ a diagnostic framework to analyse local governments' discretion and accountability in political, administrative and fiscal domains. We find that the entrenched culture of power accumulation and patronage—within which decentralisation operates—has resulted in elite capture at the local level. This along with lack of capacity at national and local levels has caused serious impediments in downward accountability of local governments. Copyright © 2010 John Wiley & Sons, Ltd.
New insights into the complex structure and ontogeny of the occipito‐vertebral gap in barbeled dragonfishes (Stomiidae, Teleostei)
Authors: Schnell Nalani K. , Britz Ralf , Johnson G. David 
Published: May 2010

AbstractIn all stomiid genera there is an occipito‐vertebral gap between the skull and the first vertebra bridged only by the flexible notochord. Morphological studies from the early 20th century suggested that some stomiid genera have 1–10 of the anteriormost centra reduced or entire vertebrae missing in this region. Our study reviews this previous hypothesis. Using a new approach, we show that only in Chauliodus, Eustomias and Leptostomias gladiator vertebral centra are actually lost, with their respective neural arches and parapophyses persisting. We present results from a comparative analysis of the number and insertion sites of the anteriormost myosepta in 26 of the 28 stomiid genera. Generally in teleosts the first three myosepta are associated with the occiput, and the fourth is the first vertebral myoseptum. The insertion site of the fourth myoseptum plays an important role in this analysis, because it provides a landmark for the first vertebra. Lack of association of the fourth myoseptum with a vertebra is thus evidence that the first vertebra is reduced or absent. By counting the occipital and vertebral myosepta the number of reduced vertebrae in Chauliodus, Eustomias and Leptostomias gladiator can be inferred. Proper identification of the spino‐occipital nerves provides an additional source of information about vertebral reduction. In all other stomiid genera the extensive occipito‐ vertebral gap is not a consequence of the reduction of vertebrae, but of an elongation of the notochord. The complex structure and ontogeny of the anterior part of the vertebral column of stomiids are discussed comparatively. J. Morphol. 271:1006–1022, 2010. © 2010 Wiley‐Liss, Inc.
Morphology and function of the hyoid apparatus of fossil xenarthrans (mammalia)
Authors: Pérez Leandro M. , Toledo Néstor , De Iuliis Gerardo , Bargo M. Susana , Vizcaíno Sergio F. 
Published: May 2010

AbstractThe analysis of the hyoid apparatus of fossil xenarthrans provides insight on the form of the tongue and its function in food intake and intraoral processing. The hyoid apparatus of xenarthrans is notable for fusion among its elements. The presence of a V‐bone, a complex consisting of fused basihyal and thyrohyal bones, is a consistent and probably synapomorphic feature of xenarthrans. Fusion of other elements is variable in fossil xenarthrans. Most fossil sloths retain independent elements, as in living dasypodids and mammals generally. Among nothrotheriids, the elements are slender and their articular surfaces indicate considerable mobility, and the relatively long and horizontal orientation of the geniohyoid muscle suggests considerable tongue protrusion. Among mylodontines, such as Paramylodon and Glossotherium, the elements indicate relatively mobile articulations, except between the stylo‐ and epihyals. The relatively posterior placement of the apparatus and the length and alignment of the geniohyoid muscle indicate considerable capacity for tongue protrusion. Scelidotherium, however, had rigidly articulated stylohyal and epihyal, and the apparatus lies farther anteriorly, which together with the elongated, steeply inclined mandibular symphysis, indicates a relatively shorter geniohyoid muscle and thus more limited capacity for tongue protrusion. A similar situation is indicated for Megatherium, casting doubt on the classical reconstruction of this sloth as having a long prehensile tongue. Among cingulates Prozaedyus resembles living dasypodids, indicating considerable tongue protrusion important in food acquisition and intake. More extensive fusion of hyoid elements occurs in the cingulates Glyptodon and Proeutatus, in which the stylohyal and epihyal at least, are fused into a single element termed the sigmohyal. The presence of this element supports recent proposals of a sister‐group relationship between glyptodonts and eutatines. The rigidity of the apparatus suggests limited tongue protrusion, but the tongue, in glyptodonts at least, was a powerful structure important for intraoral manipulation of food. J. Morphol. 271:1119–1133, 2010. © 2010 Wiley‐Liss, Inc.
Thermodynamic characterization of OsGID1‐gibberellin binding using calorimetry and docking simulations
Authors: Xiang Hongyu , Takeuchi Hiromi , Tsunoda Yuki , Nakajima Masatoshi , Murata Katsuyoshi , Ueguchi‐Tanaka Miyako , Kidokoro Shun‐ichi , Kezuka Yuichiro , Nonaka Takamasa , Matsuoka Makoto , Katoh Etsuko 
Published: May 2010

AbstractGibberellins (GAs) are phytohormones regulating various developmental processes in plants. In rice, the initial GA‐signaling events involve the binding of a GA to the soluble GA receptor protein, GID1. Although X‐ray structures for certain GID1/GA complexes have recently been determined, an examination of the complexes does not fully clarify how GID1s discriminate among different GAs. Herein, we present a study aimed at defining the types of forces important to binding via a combination of isothermal titration calorimetry (ITC) and computational docking studies that employed rice GID1 (OsGID1), OsGID1 mutants, which were designed to have a decreased possible number of hydrogen bonds with bound GA, and GA variants. We find that, in general, GA binding is enthalpically driven and that a hydrogen bond between the phenolic hydroxyl of OsGID1 Tyr134 and the C‐3 hydroxyl of a GA is a defining structural element. A hydrogen‐bond network that involves the C‐6 carboxyl of a GA that directly hydrogen bonds the hydroxyl of Ser198 and indirectly, via a two‐water‐molecule network, the phenolic hydroxyl of Tyr329 and the NH of the amide side‐chain of Asn255 is also important for GA binding. The binding of OsGID1 by GA1 is the most enthalpically driven association found for the biologically active GAs evaluated in this study. This observation might be a consequence of a hydrogen bond formed between the hydroxyl at the C‐13 position of GA1 and the main chain carbonyl of OsGID1 Phe245. Our results demonstrate that by combining ITC experiments and computational methods much can be learned about the thermodynamics of ligand/protein binding. Copyright © 2010 John Wiley & Sons, Ltd.