bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential ablation of sensory receptors underlies ototoxin‐induced shifts in auditory thresholds of the goldfish (Carassius auratus)
Authors: Ramcharitar John , Selckmann Gordon Michael 
Published: May 2010

AbstractIn recent years, fish models have become popular for investigations of ototoxic agents. However, the vast majority of such studies have focused on anatomical changes in lateral line hair cells after drug adminitration. Using the goldfish (Carassius auratus), we confirm that the acquisition of auditory evoked potentials offers a rapid and non‐invasive method for quantifying ototoxin‐induced changes in hearing sensitivity. Gentamicin (100 mg ml−1) was the drug of choice as it is a well‐studied human ototoxin. Auditory threshold elevation was observed between 300 and 600 Hz and was accompanied by significant reductions in hair cell ciliary bundle densities in specific regions of the utricle and saccule. The correlations between structure and function suggest that differential susceptibility of sensory hair cells to acute gentamicin treatment underlies the frequency‐specific elevation of auditory thresholds. We propose that fish auditory systems should be used alongside the lateral line, for the assessment of ototoxicity in new‐developed drugs. Copyright © 2010 John Wiley & Sons, Ltd.
Oxidative stress biomarkers in Cyprinus carpio exposed to commercial herbicide bispyribac‐sodium
Authors: Toni Cândida , de Menezes Charlene Cavalheiro , Loro Vania Lucia , Clasen Bárbara Estevão , Cattaneo Roberta , Santi Adriana , Pretto Alexandra , Zanella Renato , Leitemperger Jossiele 
Published: May 2010

AbstractCyprinus carpio were exposed under field conditions to 20.87 µg l−1 of commercial herbicide bispyribac‐sodium (Nominee®, SC), during 7, 21 and 72 days. Enzymatic parameters such as catalase (CAT), glutathione S‐transferase (GST) and acetylcholinesterase (AChE) activities, as well as thiobarbituric acid‐reactive substances (TBARS) and protein carbonyl contents were studied in different tissues. After 7 days of exposure, GST activity decreased. At the same period, brain AChE activity increased, but a reduction of activity was observed in muscle tissue. Brain TBARS levels increased at 7 days. After 21 days of exposure liver CAT levels and muscle AChE activities decreased. In the same period, liver protein carbonyl and muscle TBARS increased. After 72 days of exposure in the field, AChE activity was reduced in both brain and muscle. Protein carbonyl contents in liver and brain TBARS levels increased. Muscle AChE activity, TBARS and protein carbonyl can be used as biomarkers of exposure to the herbicide bispyribac‐sodium. This study demonstrates effects of exposure to bispyribac‐sodium under rice field conditions on oxidative stress parameters in tissues of Cyprinus carpio. Copyright © 2010 John Wiley & Sons, Ltd.
Femtosecond lentotomy: generating gliding planes inside the crystalline lens to regain accommodation ability
Authors: Lubatschowski Holger , Schumacher Silvia , Fromm Michael , Wegener Alfred , Hoffmann Heike , Oberheide Uwe , Gerten Georg 
Published: May 2010

AbstractBased on Helmholtz Theory for accommodation the increasing sclerosis of lens nucleus and cortex is the main cause for the developments of presbyopia. Existing therapies, however, do not reverse the stiffness of the crystalline lens and thus do not regain real accommodation ability. A new approach to restore the flexibility of the lens could be realized by photodisruption using ultrafast laser pulses. This process, known as fs‐lentotomy, was used to create micro‐incisions which act as gliding planes inside the crystalline lens without opening the eye globe. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Two step resonant Mie scattering correction of infrared micro‐spectral data: human lymph node tissue
Authors: Bird Benjamin , Miljković Miloš , Diem Max 
Published: May 2010

AbstractIn this manuscript, we report the application of EMSC to correct infrared micro‐spectral data recorded from tissue that describe resonant Mie scattering contributions. Small breast micro‐metastases previously undetectable using the raw measured spectra were provided clear contrast from the surrounding tissue after signal correction. The technique also proved transferrable, successfully correcting imaging data sets recorded from multiple patients. It is envisaged more robust methods of supervised analysis can now be constructed to automatically classify and diagnose tissue spectra. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Molecular changes during pollen germination can be monitored by Raman microspectroscopy
Authors: Schulte Franziska , Panne Ulrich , Kneipp Janina 
Published: May 2010

AbstractThe processes associated with pollen germination were studied in vitro for two tree species, Salix caprea and Fraxinus excelsior under different nutrient conditions. The results provide evidence of changes in chemical composition of the pollen grains during germination. From the comparison of spectra of the pollen grain body and the growing pollen tube, it can be concluded that there are major chemical differences between these two morphological units. Comparison of germinated and ungerminated pollen grains reveals alterations in the metabolism. Composition of the germinating pollen grain and its morphological units depends on the plant species, but also on the nutrient conditions. The results suggest species‐specific utilization of metabolite storage, and potential alterations of the pollen outer coat. Furthermore, discharge of molecules into the nutrient medium may depend on the nutrient conditions in the germination experiments. This has implications for further experiments on dynamic processes in pollen and related plant materials. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Super‐resolution imaging and statistical analysis of CdSe/CdS Core/Shell semiconductor nanocrystals
Authors: Kouskousis Betty P. , van Embden Joel , Morrish Dru , Russell Sarah M. , Gu Min 
Published: May 2010

AbstractHere we present a multifunctional algorithm. Firstly a super‐resolution method is presented for optically imaging the spatial distribution of semiconductor nanocrystals with nanometre localisation. Secondly highly resolved multiple photoluminescence trajectories of hundreds of single semiconductor nanocrystals are obtained simultaneously. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Bone density, geometry, microstructure, and stiffness: Relationships between peripheral and central skeletal sites assessed by DXA, HR-pQCT, and cQCT in premenopausal women
Authors: Liu X Sherry , Cohen Adi , Shane Elizabeth , Yin Perry T , Stein Emily M , Rogers Halley , Kokolus Shannon L , McMahon Donald J , Lappe Joan M , Recker Robert R , Lang Thomas , Guo X Edward 
Published: May 2010

Abstract
High-resolution peripheral quantitative computed tomography (HR-pQCT) is a new in vivo imaging technique for assessing 3D microstructure of cortical and trabecular bone at the distal radius and tibia. No studies have investigated the extent to which measurements of the peripheral skeleton by HR-pQCT reflect those of the spine and hip, where the most serious fractures occur. To address this research question, we performed dual-energy X-ray absorptiometry (DXA), central QCT (cQCT), HR-pQCT, and image-based finite-element analyses on 69 premenopausal women to evaluate relationships among cortical and trabecular bone density, geometry, microstructure, and stiffness of the lumbar spine, proximal femur, distal radius, and distal tibia. Significant correlations were found between the stiffness of the two peripheral sites (r = 0.86), two central sites (r = 0.49), and between the peripheral and central skeletal sites (r = 0.56–0.70). These associations were explained in part by significant correlations in areal bone mineral density (aBMD), volumetric bone mineral density (vBMD), and cross-sectional area (CSA) between the multiple skeletal sites. For the prediction of proximal femoral stiffness, vBMD (r = 0.75) and stiffness (r = 0.69) of the distal tibia by HR-pQCT were comparable with direct measurements of the proximal femur: aBMD of the hip by DXA (r = 0.70) and vBMD of the hip by cQCT (r = 0.64). For the prediction of vertebral stiffness, trabecular vBMD (r = 0.58) and stiffness (r = 0.70) of distal radius by HR-pQCT were comparable with direct measurements of lumbar spine: aBMD by DXA (r = 0.78) and vBMD by cQCT (r = 0.67). Our results suggest that bone density and microstructural and mechanical properties measured by HR-pQCT of the distal radius and tibia reflect the mechanical competence of the central skeleton. © 2010 American Society for Bone and Mineral Research.
Glucocorticoids maintain human osteoclasts in the active mode of their resorption cycle
Authors: Søe Kent , Delaissé Jean-Marie 
Published: May 2010

Abstract
Osteoclasts are known to exert their resorptive activity through a so-called resorption cycle consisting of alternating resorption and migration episodes and resulting typically in the formation of increasing numbers of discrete round excavations on bone slices. This study shows that glucocorticoids deeply modify this resorptive behavior. First, glucocorticoids gradually induce excavations with a trenchlike morphology while reducing the time-dependent increase in excavation numbers. This indicates that glucocorticoids make osteoclasts elongate the excavations they initiated rather than migrating to a new resorption site, as in control conditions. Second, the round excavations in control conditions contain undegraded demineralized collagen as repeatedly reported earlier, whereas the excavations with a trenchlike morphology generated under glucocorticoid exposure appear devoid of leftovers of demineralized collagen. This indicates that collagenolysis proceeds generally at a lower rate than demineralization under control conditions, whereas collagenolysis rates are increased up to the level of demineralization rates in the presence of glucocorticoids. Taking these observations together leads to a model where glucocorticoid-induced increased collagenolysis allows continued contact of osteoclasts with mineral, thereby maintaining resorption uninterrupted by migration episodes and generating resorption trenches. In contrast, accumulation of demineralized collagen, as prevails in controls, acts as a negative-feedback loop, switching resorptive activity off and promoting migration to a new resorption site, thereby generating an additional resorption pit. We conclude that glucocorticoids change the osteoclastic resorption mode from intermittent to continuous and speculate that this change may contribute to the early bone fragilization of glucocorticoid-treated patients. © 2010 American Society for Bone and Mineral Research.
NVP-BEZ235, a dual pan class I PI3 kinase and mTOR inhibitor, promotes osteogenic differentiation in human mesenchymal stromal cells
Authors: Martin Sally K , Fitter Stephen , Bong Li Fei , Drew Jennifer J , Gronthos Stan , Shepherd Peter R , Zannettino Andrew CW 
Published: May 2010

Abstract
Osteoblasts are bone-forming cells derived from mesenchymal stromal cells (MSCs) that reside within the bone marrow. In response to a variety of factors, MSCs proliferate and differentiate into mature, functional osteoblasts. Several studies have shown previously that suppression of the PI3K and mTOR signaling pathways in these cells strongly promotes osteogenic differentiation, which suggests that inhibitors of these pathways may be useful as anabolic bone agents. In this study we examined the effect of BEZ235, a newly developed dual PI3K and mTOR inhibitor currently in phase I–II clinical trials for advanced solid tumors, on osteogenic differentiation and function using primary MSC cultures. Under osteoinductive conditions, BEZ235 strongly promotes osteogenic differentiation, as evidenced by an increase in mineralized matrix production, an upregulation of genes involved in osteogenesis, including bone morphogenetic proteins (BMP2, -4, and -6) and transforming growth factor β1 (TGF-β1) superfamily members (TGFB1, TGFB2, and INHBE), and increased activation of SMAD signaling molecules. In addition, BEZ235 enhances de novo bone formation in calvarial organotypic cultures. Using pharmacologic inhibitors to delineate mechanism, our studies reveal that suppression of mTOR and, to a much lesser extent PI3K p110α, mediates the osteogenic effects of BEZ235. As confirmation, shRNA-mediated knockdown of mTOR enhances osteogenic differentiation and function in SAOS-2 osteoblast-like cells. Taken together, our findings suggest that BEZ235 may be useful in treating PI3K/mTOR-dependent tumors associated with bone loss, such as the hematologic malignancy multiple myeloma. © 2010 American Society for Bone and Mineral Research.
Osteosclerosis owing to Notch gain of function is solely Rbpj-dependent
Authors: Tao Jianning , Chen Shan , Yang Tao , Dawson Brian , Munivez Elda , Bertin Terry , Lee Brendan 
Published: May 2010

Abstract
Osteosclerosis is a pathologic bone disease characterized by an increase in bone formation over bone resorption. Genetic factors that contribute to the pathogenesis of this disease are poorly understood. Dysregulation or mutation in many components of the Notch signaling pathway results in a wide range of human developmental disorders and cancers, including bone diseases. Our previous study found that activation of the Notch signaling in osteoblasts promotes cell proliferation and inhibits differentiation, leading to an osteosclerotic phenotype in transgenic mice. In this study we report a longer-lived mouse model that also develops osteosclerosis and a genetic manipulation that completely rescues the phenotype. Conditionally cre-activated expression of Notch1 intracellular domain (NICD) in vivo exclusively in committed osteoblasts caused massive osteosclerosis with growth retardation and abnormal vertebrae. Importantly, selective deletion of a Notch nuclear effector—Rbpj—in osteoblasts completely suppressed the osteosclerotic and growth-retardation phenotypes. Furthermore, cellular and molecular analyses of bones from the rescued mice confirmed that NICD-dependent molecular alterations in osteoblasts were completely reversed by removal of the Rbpj pathway. Together, our observations show that the osteosclerosis owing to activation of Notch signaling in osteoblasts is canonical in nature because it depends solely on Rbpj signaling. As such, it identifies Rbpj as a specific target for manipulating Notch signaling in a cell-autonomous fashion in osteoblasts in bone diseases where Notch may be dysregulated. © 2010 American Society for Bone and Mineral Research.
Adiponectin and its association with bone mass accrual in childhood
Authors: Sayers Adrian , Timpson Nicholas J , Sattar Naveed , Deanfield John , Hingorani Aroon D , Davey-Smith George , Tobias Jon H 
Published: May 2010

Abstract
Circulating adiponectin levels are inversely related to bone mineral density (BMD) in humans and animal models. Previous studies in humans have been confined largely to adult populations, and whether adiponectin influences bone mass accrual in childhood is unclear. We examined this question using the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort by investigating relationships between circulating adiponectin levels at a mean age of 9.9 years, indices of bone mass as measured by total-body dual-energy X-ray absorptiometry (DXA) at ages 9.9 and 15.5 years, and cortical bone parameters as measured by peripheral quantitative computed tomography (pQCT) of the midtibia at age 15.5 years. A total of 4927 children were included at age 9.9 years, of whom 97% and 90% of boys and girls, respectively, were in prepuberty or early puberty, as defined by Tanner stage 1–2. A total of 2754 children were included at age 15.5 years, of whom 95% and 97% of boys and girls, respectively, were in late puberty, as defined by Tanner stage 4–5. Circulating adiponectin was found to be related to fat mass, lean mass, and, to a lesser extent, height, so analyses were adjusted for these three variables to identify possible independent effects of adiponectin on bone development. Adiponectin was inversely related to total-body-less-head bone mineral content (BMC; −3.0%), bone area (BA; −1.8%), BMC divided by BA (BMD; −4.8%), and BMC adjusted for BA by linear regression (aBMC; −5.6%), as measured at age 9.9 years (coefficients show change per doubling in adiponectin concentration, p &lt; .001). Consistent with these results, inverse associations also were seen between adiponectin and cortical BMC (−4.8%) and cortical bone area (−4.7%), as measured by tibial pQCT at age 15.5 years (p &lt; .001). Further pQCT results suggested that this inverse association of adiponectin with skeletal development predominantly involved a negative association with endosteal relative to periosteal expansion, as reflected by cortical thickness (−6.0%, p &lt; .001). We conclude that, independent of fat mass, lean mass, and height, adiponectin is associated with lower bone mass in childhood predominantly owing to an influence on relative endosteal expansion. Since these associations were observed before and after puberty, this suggests that setting of adiponectin levels in midchildhood has the potential to exert long-term effects on bone strength and fracture risk. © 2010 American Society for Bone and Mineral Research.
DMP1 C-terminal mutant mice recapture the human ARHR tooth phenotype
Authors: Jiang Baichun , Cao Zhengguo , Lu Yongbo , Janik Carol , Lauziere Stephanie , Xie Yixia , Poliard Anne , Qin Chunlin , Ward Leanne M , Feng Jian Q 
Published: May 2010

Abstract
DMP1 mutations in autosomal recessive hypophosphatemic rickets (ARHR) patients and mice lacking Dmp1 display an overlapping pathophysiology, such as hypophosphatemia. However, subtle differences exist between the mouse model and human ARHR patients. These differences could be due to a species specificity of human versus mouse, or it may be that the mutant DMP1 in humans maintains partial function of DMP1. In this study we report a deformed tooth phenotype in a human DMP1 deletion mutation case. Unexpectedly, the deletion of nucleotides 1484 to 1490 (c.1484_1490delCTATCAC, delMut, resulting in replacement of the last 18 residues with 33 random amino acids) showed a severe dentin and enamel defect similar to a dentinogenesis imperfecta (DI) III–like phenotype. To address the molecular mechanism behind this phenotype, we generated delMut transgenic mice with the endogenous Dmp1 gene removed. These mutant mice did not recapture the abnormal phenotype observed in the human patient but displayed a mild rachitic tooth phenotype in comparison with that in the Dmp1-null mice, suggesting that the DI III–like phenotype may be due to an as-yet-undetermined acquired gene modifier. The mechanism studies showed that the mutant fragment maintains partial function of DMP1 such as stimulating MAP kinase signaling in vitro. Last, the in vitro and in vivo data support a role of odontoblasts in the control of fibroblast growth factor 23 (FGF-23) regulation during early postnatal development, although this regulation on Pi homeostasis is likely limited. © 2010 American Society for Bone and Mineral Research.
Wnt10b deficiency results in age-dependent loss of bone mass and progressive reduction of mesenchymal progenitor cells
Authors: Stevens Jennifer R , Miranda-Carboni Gustavo A , Singer Meredith A , Brugger Sean M , Lyons Karen M , Lane Timothy F 
Published: May 2010

Abstract
Wnt10b is a canonical Wnt ligand expressed in developing bone and has been linked to mesenchymal progenitor functions in mice and humans. Because Wnt signaling has been shown to play an important role in progenitor maintenance in a variety of adult tissues, we examined bone deposition and growth rates throughout postnatal development in Wnt10b-null mice. Using bone histomorphometry and micro–computed tomographic (µCT) studies, we demonstrate that trabecular bone deposition is slightly enhanced in Wnt10b-null mice at 1 month of age, followed by progressive loss with age. Importantly, we find that Wnt10b is required for maintenance of adult bone density in multiple backgrounds of inbred mice and that both copies of the Wnt10b gene are required to maintain normal bone density in 6-month-old animals. We go on to show that the loss in trabecular bone in Wnt10b-null mice is associated with a reduction in the number of bone marrow–derived mesenchymal progenitors (MPCs) using in vitro colony-forming unit assays and marker analysis. Analysis of osteogenic gene expression in primary bone marrow stromal cells demonstrated reductions in expression of several osteoblast differentiation markers. Taken together, our results indicate that Wnt10b is uniquely required for maintenance of mesenchymal progenitor activity in adult bone. The results show the significance of studying individual Wnt ligands and their potentially unique contribution in the context of aging and disease. © 2010 American Society for Bone and Mineral Research.
Efficacy and safety of a once-yearly i.v. Infusion of zoledronic acid 5 mg versus a once-weekly 70-mg oral alendronate in the treatment of male osteoporosis: A randomized, multicenter, double-blind, active-controlled study
Authors: Orwoll Eric S , Miller Paul D , Adachi Jonathan D , Brown Jacques , Adler Robert A , Kendler David , Bucci-Rechtweg Christina , Readie Aimee , Mesenbrink Peter , Weinstein Robert S 
Published: May 2010

Abstract
Zoledronic acid (ZOL) has shown beneficial effects on bone turnover and bone mineral density (BMD) in postmenopausal osteoporosis. This study compared the efficacy and safety of a once-yearly i.v. infusion of ZOL with weekly oral alendronate (ALN) in men with osteoporosis. In this multicenter, double-blind, active-controlled, parallel-group study, participants (n = 302) were randomized to receive either once-yearly ZOL 5 mg i.v. or weekly oral ALN 70 mg for 24 months. Changes in BMD and bone marker levels were assessed. ZOL increased BMD at the lumbar spine, total hip, femoral neck, and trochanter and was not inferior to ALN at 24 months [least squares mean estimates of the percentage increases in lumbar spine BMD of 6.1% and 6.2%; difference approximately 0.13; 95% confidence interval (CI) 1.12–0.85 in the ZOL and ALN groups, respectively]. At month 12, the median change from baseline of markers for bone resorption [serum β-C-terminal telopeptide of type I collagen (β-CTx) and urine N-terminal telopeptide of type I collagen (NTx)] and formation [serum N-terminal propeptide of type I collagen (P1NP) and serum bone-specific alkaline phosphatase (BSAP)] were comparable between ZOL and ALN groups. Most men preferred i.v. ZOL over oral ALN. The incidence of adverse events and serious adverse events was similar in the treatment groups. It is concluded that a once-yearly i.v. infusion of ZOL 5 mg increased bone density and decreased bone turnover markers similarly to once-weekly oral ALN 70 mg in men with low bone density. © 2010 American Society for Bone and Mineral Research.