bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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

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

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

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 < .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 < .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 < .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

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

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

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.
Independent clinical validation of a Canadian FRAX tool: Fracture prediction and model calibration
Authors: Leslie William D , Lix Lisa M , Johansson Helena , Oden Anders , McCloskey Eugene , Kanis John A
Published: May 2010

A FRAX model for Canada was constructed for prediction of osteoporotic and hip fracture risk using national hip fracture data with and without the use of femoral neck bone mineral density (BMD). Performance of this system was assessed independently in a large clinical cohort of 36,730 women and 2873 men from the Manitoba Bone Density Program database that tracks all clinical dual-energy X-ray absorptiometry (DXA) test results for the Province of Manitoba, Canada. Linkage with other provincial health databases allowed for the direct comparison of fracture risk estimates from the Canadian FRAX model with observed fracture rates to 10 years (549 individuals with incident hip fractures and 2543 with incident osteoporotic fractures). The 10-year Kaplan-Meier estimate for hip fractures in women was 2.7% [95% confidence interval (CI) 2.1–3.4%] with a predicted value of 2.8% for FRAX with BMD, and in men the observed risk was 3.5% (95% CI 0.8–6.2%) with predicted value of 2.9%. The 10-year estimate of osteoporotic fracture risk for all women was 12.0% (95% CI 10.8–13.4%) with a predicted value of 11.1% for FRAX with BMD, and in men, the observed risk was 10.7% (95% CI 6.6–14.9%) with a predicted value of 8.4%. Discrepancies were observed within some subgroups but generally were small. Fracture discrimination based on receiver operating characteristic curve analysis was comparable with published meta-analyses with area under the curve for osteoporotic fracture prediction of 0.694 (95% CI 0.684–0.705) for FRAX with BMD and for hip fractures 0.830 (95% CI 0.815–0.846), both of which were better than FRAX without BMD or BMD alone. Individual risk factors considered by FRAX made significant independent contributions to fracture prediction in one or more of the models. In conclusion, a Canadian FRAX tool calibrated on national hip fracture data generates fracture risk predictions that generally are consistent with observed fracture rates across a wide range of risk categories. © 2010 American Society for Bone and Mineral Research.
Association between bone turnover rate and bone microarchitecture in men: The STRAMBO study
Authors: Chaitou Ali , Boutroy Stephanie , Vilayphiou Nicolas , Munoz Françoise , Delmas Pierre D , Chapurlat Roland , Szulc Pawel
Published: May 2010

Few data concern the relationship between bone turnover and microarchitecture in men. We investigated the association between levels of biochemical markers of bone turnover (BTM) and bone microarchitecture in 1149 men aged 19 to 85 years. Bone microarchitecture was assessed by high-resolution peripheral quantitative computed tomography at the distal radius and tibia. Bone formation was assessed by serum osteocalcin, bone alkaline phosphatase, and N-terminal extension propeptide of type I collagen. Bone resorption was assessed by serum C-terminal telopeptide of type I collagen and urinary excretion of total deoxypyridinoline. BTM levels were high in young men and decreased until age 50 years. Urinary deoxypyridinoline (DPD) increased after age 70 years, whereas other BTMs remained stable. Before 50 years of age, only cortical volumetric bone mineral density (Dcort) correlated negatively with BTM levels. Between 50 and 70 years of age, Dcort and some microarchitectural parameters correlated significantly with BTM at the radius and tibia. After 70 years of age, higher BTM levels were associated with lower cortical thickness and Dcort at both the skeletal sites. At the distal radius, men in the highest BTM quartile had lower trabecular density, number (Tb.N), and thickness (Tb.Th) and more heterogeneous trabecular distribution compared with men in the lower quartiles. At the distal tibia, higher BTM levels were associated with lower Tb.N and Tb.Th in the central but not subendocortical area. Thus, in men, bone microarchitecture depends weakly on the current bone turnover rate until age 70. Thereafter, bone turnover seems to be a significant determinant of bone microarchitecture. © 2010 American Society for Bone and Mineral Research.
Early-onset, progressive, frequent, extensive, and severe bone mineral and renal complications in multiple endocrine neoplasia type 1–associated primary hyperparathyroidism
Authors: Lourenço Delmar M , Coutinho Flavia L , Toledo Rodrigo A , Montenegro Fabio LM , Correia-Deur Joya EM , Toledo Sergio PA
Published: May 2010

Differences in bone mineral density (BMD) patterns have been recently reported between multiple endocrine neoplasia type 1–related primary hyperparathyroidism (HPT/MEN1) and sporadic primary HPT. However, studies on the early and later outcomes of bone/renal complications in HPT/MEN1 are lacking. In this cross-sectional study, performed in a tertiary academic hospital, 36 patients cases with uncontrolled HPT from 8 unrelated MEN1 families underwent dual-energy X-ray absorptiometry (DXA) scanning of the proximal one-third of the distal radius (1/3DR), femoral neck, total hip, and lumbar spine (LS). The mean age of the patients was 38.9 ± 14.5 years. Parathyroid hormone (PTH)/calcium values were mildly elevated despite an overall high percentage of bone demineralization (77.8%). In the younger group (<50 years of age), demineralization in the 1/3DR was more frequent, more severe, and occurred earlier (40%; Z-score −1.81 ± 0.26). The older group (>50 years of age) had a higher frequency of bone demineralization at all sites (p < .005) and a larger number of affected bone sites (p < .0001), and BMD was more severely compromised in the 1/3DR (p = .007) and LS (p = .002). BMD values were lower in symptomatic (88.9%) than in asymptomatic HPT patients (p < .006). Patients with long-standing HPT (>10 years) and gastrinoma/HPT presented significantly lower 1/3DR BMD values. Urolithiasis occurred earlier (<30 years) and more frequently (75%) and was associated with related renal comorbidities (50%) and renal insufficiency in the older group (33%). Bone mineral– and urolithiasis-related renal complications in HPT/MEN1 are early-onset, frequent, extensive, severe, and progressive. These data should be considered in the individualized clinical/surgical management of patients with MEN1-associated HPT. © 2010 American Society for Bone and Mineral Research.
Increased osteocyte death and mineralization inside bone after parathyroidectomy in patients with secondary hyperparathyroidism
Authors: Yajima Aiji , Inaba Masaaki , Tominaga Yoshihiro , Nishizawa Yoshiki , Ikeda Kyoji , Ito Akemi
Published: May 2010

In order to gain insight into the mechanisms underlying the dynamic changes in bone metabolism and bone quality after parathyroidectomy (PTX) in secondary hyperparathyroid patients with high levels of parathyroid hormone (PTH), we performed bone histomorphometric analysis with tetracycline labeling in iliac bone biopsy specimens taken before and after PTX, with special attention paid to osteocytes. At 2 to 4 weeks after PTX, PTH concentrations decreased markedly with evident reductions in bone turnover markers. Histomorphometry revealed that at 2 to 4 weeks following PTX, the osteoclast surface decreased to nearly 0%, with a substantial increase in osteoid volume and a reduction in fibrosis volume. Labeling with tetracycline was observed not only at the mineralization front on the bone surface but also around the osteocyte lacunar walls and canaliculi within both the basic multicellular units (BMUs) and bone structural units (BSUs), suggesting that mineralization was taking place along the lacunocanalicular system after PTX. The tetracycline-labeled area was much greater in the BSUs than in the BMUs and at the mineralization front, and the tetracycline labeling in the BSUs was markedly increased after PTX compared with that in the low- and high-PTH control groups without PTX. The osteocyte number was decreased significantly after PTX, concomitant with an increase in the number of empty lacunae and a reduction of lacunar volume. Thus the increased osteocyte death and mineralization around the lacunocanalicular system in association with a rapid decline in PTH may underlie the changes in bone metabolism and quality that occur following PTX. © 2010 American Society for Bone and Mineral Research.
Gene expression of growth hormone family and glucocorticoid receptors, osmosensors, and ion transporters in the gill during seawater acclimation of Mozambique tilapia, Oreochromis mossambicus
Authors: Breves Jason P. , Fox Bradley K. , Pierce Andrew L. , Hirano Tetsuya , Grau E. Gordon
Published: May 2010

This study characterized endocrine and ionoregulatory responses accompanying seawater (SW) acclimation in Mozambique tilapia (Oreochromis mossambicus). Changes in plasma hormones and gene expression of hormone receptors, putative osmosensors, and ion transporters in the gill were measured. Transfer of freshwater (FW)‐acclimated tilapia to SW resulted in a marked elevation in plasma osmolality and a significant rise in plasma growth hormone (GH) levels at 12 hr and 14 days after transfer. Significant reductions in plasma prolactin (PRL177 and PRL188) levels also occurred in SW‐transferred fish; no effect of transfer upon plasma cortisol or insulin‐like growth factor I was observed. Gene expression of GH receptor increased strongly 6 hr after transfer, whereas PRL receptor was lower than controls at 12 hr. By contrast, mRNA levels of somatolactin and glucocorticoid receptors were unaffected by SW transfer. Osmotic stress transcription factor 1 mRNA levels rose significantly between 3 and 12 hr, whereas the calcium‐sensing receptor was unaffected. Aquaporin‐3 gene expression was strongly down‐regulated during SW acclimation from 12 hr until the conclusion of the experiment. Na+/K+/2Cl− cotransporter gene expression increased significantly 3 hr after transfer, whereas expression of Na+/Cl− cotransporter, specific to FW‐type chloride cells, declined by 6 hr into SW acclimation. The response of Na+/H+ exchanger was less pronounced, but showed a similar pattern to that of the Na+/Cl− cotransporter. These results suggest that acquisition of hyposmoregulatory mechanisms in Mozambique tilapia entails the coordinated interaction of systemic hormones with local factors in the gill, including hormone receptors, ion transporters, and osmosensors. J. Exp. Zool. 313A:432–441, 2010. © 2010 Wiley‐Liss, Inc.
Morphological correlates of sprint swimming speed in five species of spadefoot toad tadpoles: Comparison of morphometric methods
Authors: Arendt Jeff
Published: May 2010

The relationship between vertebrate morphology and swimming performance has long interested biologists. Recent work on predator‐induced morphological plasticity of anuran tadpoles has increased this interest. Here, I use data on five species of spadefoot toad tadpoles (Scaphiopodidae) to compare linear and geometric morphometrics. Linear measures explain only 7–26% of the variation in swimming speed, depending on species, whereas geometric morphometrics could explain 24–46% of the same variation. I also compare two methods for examining how similar the morphology–swimming speed relationship is among species. A canonical variate derived from a MANCOVA approach successfully detected species differences in these relationships, whether using linear or geometric methods, but a canonical correlation approach failed in both cases. Overall, tadpoles with smaller bodies, larger tails, and larger tail muscles are faster swimmers but the details of how these shape changes are achieved differed among species. For example, in some species a smaller body was achieved primarily by reducing abdomen size, whereas in others both the head and abdomen are smaller.

Faster swimmers also had deeper tails, especially in the posterior half of the tail. This pattern would have been missed in standard linear morphometrics which usually only measures maximum tail depth. J. Morphol. 271:1044‐1052, 2010. © 2010 Wiley‐Liss, Inc.
Selective cleavage of protonated penetratin and its substitutes under low‐energy collision‐induced dissociation condition
Authors: Peng Juan , Zu Lily , Fang Weihai , Huang Lingyun , Wang Yaru , He Dacheng
Published: May 2010

An understanding of the dissociation of penetratin is important for improving its metabolic stability and cargo‐delivery efficiency. In this study, we describe the selective cleavage of the K15–K16 amide bond of penetratin under the low‐energy collision‐induced dissociation condition in mass spectrometry. A variety of penetratin substitutes have been studied in which key basic amino acids have been substituted within the sequence. The calculated structure indicates that an α‐helix structure prevents the fragmentation of the central peptide domain and the side chain of lysine is involved in the proton translocation process. Copyright © 2010 John Wiley & Sons, Ltd.
Best‐practice recommendations for estimating interaction effects using moderated multiple regression
Authors: Aguinis Herman , Gottfredson Ryan K.
Published: May 2010

An interaction effect indicates that a relationship is contingent upon the values of another (moderator) variable. Thus, interaction effects describe conditions under which relationships change in strength and/or direction. Understanding interaction effects is essential for the advancement of the organizational sciences because they highlight a theory's boundary conditions. We describe procedures for estimating and interpreting interaction effects using moderated multiple regression (MMR). We distill the technical literature for a general readership of organizational science researchers and include specific best‐practice recommendations regarding actions researchers can take before and after data collection to improve the accuracy of MMR‐based conclusions regarding interaction effects. Copyright © 2010 John Wiley & Sons, Ltd.
Bivariate colour maps for visualizing climate data
Authors: Teuling A. J. , Stöckli R. , Seneviratne S. I.
Published: May 2010

The increasing availability of gridded, high‐resolution, multivariate climatological data sets calls for innovative approaches to visualize inter‐variable relations. In this study, we present a methodology, based on properties of common colour schemes, to plot two variables in a single colour map by using a two‐dimensional colour legend for both sequential and diverging data. This is especially suited for climate data as the spatial distribution of the relation between different variables is often as important as the distribution of variables individually. Two example applications are given to illustrate the use of the method: one that shows the global distribution of climate based on observed temperature and relative humidity, and the other showing the distribution of recent changes in observed temperature and precipitation over Europe. A flexible and easy‐to‐implement method is provided to construct different colour legends for sequential and diverging data. Copyright © 2010 Royal Meteorological Society
Speciation of inorganic and tetramethyltin by headspace solid‐phase microextraction and gas chromatography–mass spectrometry
Authors: Tzollas Nikolaos M. , Zachariadis George A.
Published: May 2010

A headspace solid‐phase microextraction (HS‐SPME) method coupled to GC‐MS was developed in order to determine trace levels of tetramethyltin (TeMT) and inorganic tin (iSn) after ethylation to tetraethyltin (TeET) in various matrices. The derivatization of iSn and the extraction of both TeMT and iSn as TeET were performed in one step. Sodium tetraethylborate (NaBEt4) was used as derivatization agent and the volatile derivatives were absorbed on a PDMS‐coated fused silica fiber. The conditions for the HS‐SPME procedure were optimized in order to gain in repeatability and sensitivity. Several critical parameters of GC‐MS were also studied. The detection of TeMT and iSn as TeET peaks was performed by the SIM mode. The precision of the proposed method is satisfactory providing RSD values below 10% for both tin species and good linearity up to 10 μg/L. The developed method was successfully applied to the determination of tin species in several samples like canned fish, fish tissues, aquatic plants, canned mineral water and sea water. The proposed HS‐SPME‐GC‐MS method was proved suitable to monitor the concentration levels of toxic tin compounds in environmental and biological samples.
Silica‐based zwitterionic monolithic stationary phase for separation of neutral and ionized solutes using pressurized CEC
Authors: Huang Guihua , Zeng Wencan , Lin Xucong , Xie Zenghong
Published: May 2010

A porous zwitterionic monolith was prepared by in situ covalent attachment of lysine to a γ‐glycidoxypropyltrimethosysilane‐modified silica monolith. The prepared column was used to perform neutral and ionized solutes separations by pressurized (pCEC). Due to the zwitterionic nature of the resulting stationary phase, the monolithic column provided both electrostatic attraction and repulsion sites for electrochromatographic retention for ionized solutes. Separation of several nucleotides was investigated on the monolithic column. It was shown that the nucleotides could be separated based on hydrophilic and electrostatic interactions between the stationary phase and analyte. Besides, the separation property of the zwitterionic silica monolith was compared with the use of diamine‐bonded silica monolith as stationary phase. As expected, the lysine monolith exhibited a lower retention for the five nucleotides, which was due to the dissociation of the external carboxylic acid groups, leading to electrostatic repulsion with negatively charged solutes. Under the same experimental conditions, separation of the five nucleotides on the zwitterionic column was in less than 8 min, while that on the diamine column was in approximately 60 min.
Solid‐phase extraction of matrine and oxymatrine from Sophora Flavescens Ait using amino‐imidazolium polymer
Authors: Bi Wentao , Tian Minglei , Row Kyung Ho
Published: May 2010

A new, polymer‐confined, ionic liquid sorbent was developed by a process involving polymerization and modification. The obtained particles were successfully used as a special sorbent in SPE process to isolate matrine and oxymatrine from Sophora Flavescens Ait. Different washing and elution solvents, such as ethanol, methanol, acetonitrile and methanol/triethylamine (90:10, v/v), were evaluated. Compared with the C18 and NH2 sorbents, the amino‐imidazolium polymer sorbent exhibited higher selectivity. Quantitative analysis was carried out by using a C18 column. The two compounds exhibited good linearity from 5×10−3 to 0.50 mg/mL (r2>0.99). The bound amounts between target compounds and proteins were obtained by this sorbent. After three recycles of amino‐imidazolium polymer, the extract amounts of the target compounds were not significantly decreased.
Semi‐preparative high‐speed counter‐current chromatography separation of alkaloids from embryo of the seed of Nelumbo nucifera Gaertn by pH‐gradient elution
Authors: Duanmu Qingping , Li Aifeng , Sun Ailing , Liu Renmin , Li Xiaopeng
Published: May 2010

A new high‐speed counter‐current chromatography method for semi‐preparative separation and purification of alkaloids from embryo of the seed of Nelumbo nucifera Gaertn was developed by using pH‐gradient elution mode. Diethyl ether was used as the stationary phase of the two‐phase solvent system and Na2HPO4/NaH2PO4 buffer solution with pH values of 7.5 and 7.2 in gradient mode as the mobile phase. Consequently, 33 mg of liensinine, 42 mg of isoliensinine, and 67 mg of neferine were obtained from 200 mg of crude extracts. The purities of them were all over 98% as determined by HPLC area normalization method, and the structures were identified by 1H‐NMR and 13C‐NMR.
Potential‐driven peptide extractions across supported liquid membranes: Investigation of principal operational parameters
Authors: Balchen Marte , Jensen Henrik , Reubsaet Léon , Pedersen‐Bjergaard Stig
Published: May 2010

Fundamental experiments on electromembrane extraction were performed to increase the basic knowledge about the current and the mass transfer of target peptides and background electrolyte ions. Three peptides (angiotensin 2, bradykinin, and enkephalin) were extracted from 500 μL aqueous donor solution (1 mM HCl, positive electrode), through a 200 μm supported liquid membrane (SLM) of 1‐octanol/di‐isobutylketon/di‐(2‐ethylhexyl) phosphate (55:35:10 w/w/w) sustained in the pores of a porous hollow fiber, and into 25 μL aqueous acceptor solution (50 mM HCl, negative electrode) present inside the lumen of the fiber by the application of an electrical potential (50 V) and agitation (1050 rpm). Recoveries were typically in the range of 55–65% after 5 min of extraction and were principally determined by the chemical composition of the SLM and by the applied voltage. The electrical current in the system was measured during the extraction and was close to 350 μA. The current arose to some extent from mass transfer of the target peptides, but the major contribution was due to a background current from di‐(2‐ethylhexyl) phosphate in the SLM and from mass transfer of background electrolytes. Operation at relatively low background current was important to maintain a stable system.
Simultaneous determination of anthracyclines and taxanes in human serum using online sample extraction coupled to high performance liquid chromatography with UV detection
Authors: Bermingham Shane , O'Connor Robert , Regan Fiona , McMahon Gillian P.
Published: May 2010

An online SPE‐LC method that can determine both anthracyclines and taxanes simultaneously in human serum samples is reported. The entire method of extraction, separation and UV detection was achieved online by column switching between an SPE column (Biotrap 500 (20×4 mm)) and an analytical column (Zorbax XDB C18, 150×4.6 mm, 5 μm) with a 23 min total cycle time. The method is linear (r2>0.998) over the range of 0.5–25 μg/mL. The analytes of interest are retained on the SPE column with good recovery (84–117%), while proteins and other serum components elute to waste. This online clean‐up is much faster (150 s) and less manual than traditional off‐line extraction methods. Using 0.1 mL spiked serum samples, the LOQ was 0.5 μg/mL. Intra‐ and inter‐day precision were acceptable (≤15% RSD) at and above the LOQ. The method was applied to the analysis of serum samples from patients undergoing chemotherapy with these agents.
HPLC‐DAD method for the simultaneous determination of zofenopril and hydrochlorothiazide in oral pharmaceutical formulations
Authors: Carlucci Giuseppe , Di Federico Lucia , Iuliani Piera
Published: May 2010

An HPLC method with DAD detection was developed and validated for the simultaneous determination of zofenopril and hydrochlorothiazide in tablets. The separation was carried out through a gradient elution using an Agilent LiChrospher C18 column (250×4.0 mm id, 5 μm) and a mobile phase consisting of (A) water–TFA (99.9:0.1 v/v) and (B) acetonitrile–TFA (99.1:0.1 v/v) delivered at a flow‐rate of 1.0 mL/min. 8‐Chlorotheophylline was used as internal standard. Calibration curves were found to be linear for the two drugs over the concentration ranges of 5.0–40 and 1.0–20 μg/mL for zofenopril and hydrochlorothiazide, respectively. Linearity, precision, accuracy, specificity and robustness were determined in order to validate the proposed method, which was further applied to the analysis of commercial tablets. The proposed method is simple and rapid, and gives accurate and precise results.
Direct Microfabrication of Topographical and Chemical Cues for the Guided Growth of Neural Cell Networks on Polyamidoamine Hydrogels
Authors: Dos Reis Gabriel , Fenili Fabio , Gianfelice Antonella , Bongiorno Gero , Marchesi Davide , Scopelliti Pasquale Emanuele , Borgonovo Antonio , Podestà Alessandro , Indrieri Marco , Ranucci Elisabetta , Ferruti Paolo , Lenardi Cristina , Milani Paolo
Published: May 2010

Cell patterning is an important tool for organizing cells in surfaces and to reproduce in a simple way the tissue hierarchy and complexity of pluri‐cellular life. The control of cell growth, proliferation and differentiation on solid surfaces is consequently important for prosthetics, biosensors, cell‐based arrays, stem cell therapy and cell‐based drug discovery concepts. We present a new electron beam lithography method for the direct and simultaneous fabrication of sub‐micron topographical and chemical patterns, on a biocompatible and biodegradable PAA hydrogel. The localized e‐beam modification of a hydrogel surface makes the pattern able to adsorb proteins in contrast with the anti‐fouling surface. By also exploiting the selective attachment, growth and differentiation of PC12 cells, we fabricated a neural network of single cells connected by neuritis extending along microchannels. E‐beam microlithography on PAA hydrogels opens up the opportunity of producing multifunctional microdevices incorporating complex topographies, allowing precise control of the growth and organization of individual cells.

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Donor–π–Acceptor Polymer with Alternating Triarylborane and Triphenylamine Moieties
Authors: Li Haiyan , Jäkle Frieder
Published: May 2010

A luminescent main chain donor–π–acceptor‐type polymer (4) was prepared via organometallic polycondensation reaction followed by post modification. With both electron‐rich amine and electron‐deficient borane moieties embedded in the main chain, 4 exhibits an interesting ambipolar character: it can be reduced and oxidized electrochemically at moderate potentials and shows a strong solvatochromic effect in the emission spectra. Complexation studies show that 4 selectively binds to fluoride and cyanide; quantitative titration with cyanide reveals a two‐step binding process.

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Radical Desorption Kinetics in Emulsion Polymerization, 2 – Brownian Dynamics Simulation of Radical Desorption in Non‐Homogeneous Particles
Authors: Hernandez Hugo F. , Tauer Klaus
Published: May 2010

One of the most important events in free‐radical emulsion polymerization is desorption of radicals from the polymer particles to the aqueous phase. Desorption takes place by diffusion of radicals inside the particle toward the surface and transfer to the aqueous phase. The rate of desorption can be determined theoretically for homogeneous spherical particles. For more complex cases, analytical solutions become difficult or impossible to obtain and a numerical approach is better suited for estimating desorption rate coefficients. In this paper, Brownian dynamics simulation is used for the estimation of desorption rate coefficients in emulsion polymerization systems of increased complexity, in particular for non‐homogeneous polymer particles.

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The equine oocyte: Factors affecting meiotic and developmental competence
Authors: Hinrichs Katrin
Published: May 2010

There is currently much interest in assisted reproduction techniques in the horse, however, many aspects of oocyte maturation, fertilization, and embryo development in the horse differ from those in other species. Because of the close attachment of the equine oocyte to the follicle wall, scraping of the follicle is the most effective method for oocyte recovery. A notable feature of equine oocytes is that those with expanded cumuli (Ex oocytes), which originate from atretic follicles, have higher meiotic competence (ability to mature to metaphase II in vitro) than do oocytes with compact cumuli (Cp oocytes). Cp oocytes originate in viable follicles but are largely juvenile. Recovery and culture of equine oocytes immediately after slaughter yields a higher maturation rate than that obtained from oocytes after ovary storage; this is related to damage to chromatin in Cp oocytes during storage. In contrast, developmental competence (rate of blastocyst development in vitro) is higher in oocytes recovered from the ovary after a delay. The optimum duration of maturation varies based on cumulus morphology and time of recovery from the ovary, but there is no difference in developmental competence between Ex and Cp oocytes. Because standard in vitro fertilization is not repeatable in the horse, oocyte transfer (surgical transfer of oocytes to the oviducts of inseminated mares) has been developed to allow fertilization of isolated oocytes. Fertilization in vitro may be achieved using intracytoplasmic sperm injection; culture of injected oocytes in a medium with high glucose can yield over 30% blastocyst development. Mol. Reprod. Dev. 77: 651–661, 2010. © 2010 Wiley‐Liss, Inc.
Dual‐band water and lipid suppression for MR spectroscopic imaging at 3 Tesla
Authors: Zhu He , Ouwerkerk Ronald , Barker Peter B.
Published: May 2010

A dual‐band water and lipid suppression sequence was developed for multislice sensitivity‐encoded proton MR spectroscopic imaging of the human brain. The presaturation scheme consisted of five dual‐band frequency‐modulated radiofrequency pulses based on hypergeometric functions integrated with eight outer volume suppression (OVS) pulses. The flip angles of the dual‐band pulses were optimized through computer simulations to maximize suppression factors over a range of transmitter amplitude of radiofrequency field and water and lipid T1 values. The resulting hypergeometric dual band with OVS (HGDB + OVS) sequence was implemented at 3 T in a multislice sensitivity‐encoded proton MR spectroscopic imaging experiment and compared to a conventional water suppression scheme (variable pulse power and optimized relaxation delays (VAPOR)) with OVS. The HGDB sequence was significantly shorter than the VAPOR sequence (230 versus 728 msec). Both HGDB + OVS and VAPOR + OVS produced good water suppression, while lipid suppression with the HGDB + OVS sequence was far superior. In sensitivity‐encoded proton MR spectroscopic imaging data, artifacts from extracranial lipid signals were significantly lower with HGDB + OVS. The shorter duration of HGDB compared to VAPOR also allows reduced pulse repetition time values in the multislice acquisition. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
An efficient gridding reconstruction method for multishot non‐Cartesian imaging with correction of off‐resonance artifacts
Authors: Meng Yuguang , Lei Hao
Published: May 2010

An efficient iterative gridding reconstruction method with correction of off‐resonance artifacts was developed, which is especially tailored for multiple‐shot non‐Cartesian imaging. The novelty of the method lies in that the transformation matrix for gridding (T) was constructed as the convolution of two sparse matrices, among which the former is determined by the sampling interval and the spatial distribution of the off‐resonance frequencies and the latter by the sampling trajectory and the target grid in the Cartesian space. The resultingTmatrix is also sparse and can be solved efficiently with the iterative conjugate gradient algorithm. It was shown that, with the proposed method, the reconstruction speed in multiple‐shot non‐Cartesian imaging can be improved significantly while retaining high reconstruction fidelity. More important, the method proposed allows tradeoff between the accuracy and the computation time of reconstruction, making customization of the use of such a method in different applications possible. The performance of the proposed method was demonstrated by numerical simulation and multiple‐shot spiral imaging on rat brain at 4.7 T. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.