bluuebunny/crossref_metadata_2025 huggingface dataset:
Mast cell stabilization: novel medication for obesity and diabetes
Authors: Wang Jing , Shi Guo‐Ping
Published: November 2011

Mast cells are essential in allergic responses and beyond. White adipose tissue from obese humans contains large numbers of mast cells. Serum mast cell tryptase levels are also significantly higher in obese subjects than in lean subjects, suggesting a role of these inflammatory cells in obesity and diabetes. Two types of mast cell‐deficient mice, along with corresponding wild‐type control mice, were fed a Western diet to induce obesity and diabetes. We also used two anti‐allergy drugs, cromolyn and ketotifen (Zaditor), to treat wild‐type mice during intake of a Western diet or after the onset of obesity and diabetes, to examine the possible prevention or reversal of these conditions. Mast cell deficiency or pharmacological stabilization reduced body weight gain and improved glucose and insulin sensitivities. These common, side effect‐free drugs also reduced pre‐established obesity and diabetes without noticeable toxicity. Mechanistic studies suggest that mast cells participate in these metabolic disorders by affecting energy expenditure, protease expression, angiogenesis, apoptosis, and preadipocyte differentiation. These observations open a new era of basic research regarding mast cells, and offer hope to patients suffering from these metabolic disorders. Copyright © 2011 John Wiley & Sons, Ltd.
‘Sensing’ the link between type 1 and type 2 diabetes
Authors: Tsui Hubert , Paltser Geoffrey , Chan Yin , Dorfman Ruslan , Dosch H. Michael
Published: November 2011

Obesity‐associated insulin resistance is a core element of metabolic syndrome and type 2 diabetes (T2D). Notably, insulin resistance is also a feature of type 1 diabetes (T1D), where findings in the non‐obese diabetic mouse model have implicated transient receptor potential vanilloid‐1 (TRPV1+) sensory neurons in local islet inflammation and glucose metabolism. Here, we briefly review the role of TRPV1 in non‐obese diabetic (NOD) T1D pathogenesis, highlighting commonalities that suggest TRPV1 may contribute to obesity and T2D as well. With the recently discovered importance of adipose infiltrating lymphocytes in the metabolic disturbances of obesity and T2D, sensory innervation of fat may thus play an analogous role to sensory neurons in the islet—modulating neuroendocrine homeostasis and inflammation. In such a scenario, TRPV1+ sensory nerves would provide the pathoaetiological link connecting the shared metabolic and immunologic features of type 1 diabetes and T2D. Copyright © 2011 John Wiley & Sons, Ltd.
Prevention of type 1 diabetes by inducing subclinical dermatitis on a small area
Authors: Engkilde Kaare , Johansen Jeanne Duus , Hansen Axel Kornerup , Menné Torkil , Buschard Karsten
Published: November 2011

Objective

We have previously epidemiologically shown that type 1 diabetes is inversely associated with contact allergy. This finding is intriguing as type 1 diabetes and contact allergy are two completely different diseases, although T cells are involved in both diseases. The objective of this study was therefore to experimentally study the effect of contact allergens on the development of diabetes in non‐obese diabetic mice.

Methods

Non‐obese diabetic mice 4 weeks of age were separated into seven groups. One group was exposed to tapped water every 14th day, whereas the remaining six groups were split into sensitizations groups or elicitation groups (exposure every 14th day). These groups were then treated with one of the selected contact allergens (PPD or DNCB) or vehicle (AOO). All groups received the sensitizing treatment regime, and hereafter only the elicitation groups were further treated. If the blood glucose reached 14 mM, the mice were considered diabetic and euthanized. Cardiac heart blood was drawn at euthanization, and a Luminex analysis was done on the serum.

Results

We showed that repeated application of a low dose of PPD reduced the incidence of diabetes compared to application with water (47% versus 93%, p = 0.004). The rest of the groups developed diabetes with a cumulative incidence rate above 80%. The Luminex cytokine analysis revealed no differences between the groups, and no elevated cytokine level suggested a systemic response. Dermatitis was not noticeable by visual inspection, a histological examination, however, revealed a slight infiltration in the ears in the elicitation groups exposed to contact allergens.

Conclusion

This study showed that repeated topical application on the ears with a contact allergen could prevent the development of diabetes in non‐obese diabetic mice. The contact allergens gave a non‐visible, subclinical dermatitis on the application site. Activation of NKT cells to the ear lymph nodes seems to be involved. Copyright © 2011 John Wiley & Sons, Ltd.
Two promoters with distinct activities in different tissues drive the expression of heparanase in Xenopus
Authors: Bertolesi Gabriel E. , Su Hsiao Yuan , Michaiel George , Dueck Stephanie M. , Hehr Carrie L. , McFarlane Sarah
Published: November 2011

In Xenopus laevis embryos, heparanase, the enzyme that degrades heparan sulfate, is synthesized as a preproheparanase (XHpaL) and processed to become enzymatically active (XHpa active). A short nonenzymatic heparanase splice variant (XHpaS) is also expressed. Using immunohistochemistry, Western blot, and heparanase promoter analysis, we studied the dynamic developmental expression of the three heparanases. Our results indicate that (1) all three isoforms are maternally expressed; (2) XHpaS is a developmental variant; (3) in the early embryo, heparanase is localized to both the plasma membrane and the nucleus; (4) several tissues express heparanase, but expression in the developing nervous system is most evident; (5) two promoters with distinct activities in different tissues drive heparanase expression; (6) Oct binding transcription factors may modulate heparanase promoter activity in the early embryo. These data argue that heparanase is expressed widely during development, but localization and levels are finely regulated. Developmental Dynamics 240:2657–2672, 2011. © 2011 Wiley Periodicals, Inc.
Lipid oxidation inhibiting capacities of blackseed essential oil and rosemary extract
Authors: Erkan Naciye , Ayranci Guler , Ayranci Erol
Published: November 2011

Lipid oxidation is the main deterioration process that occurs in vegetable oils containing lipid molecules with polyunsaturation. The aim of the present study was to investigate the possible effects of blackseed (Nigella sativa L.) essential oil (BEO) and rosemary (Rosmarinus officinalis L.) extract (RE) on stabilization of sunflower oil under accelerated storage conditions. RE was obtained by soxhlet extraction using methanol, whereas BEO was hydrodistilled from the blackseed extract obtained by extraction using petroleum ether (b.p. 40–60°C). The results indicate that both extracts stabilize sunflower oil to a certain extent, the extent being greater with RE than with BEO based on measurements of peroxide value, p‐anisidine value, amount of nonoxidized linoleic acid in saponified oil samples by HPLC‐DAD, concentration of conjugated diene hydroperoxide, and UV light absorption. The oil stabilizing effect of BEO against lipid oxidation, especially at concentrations of 0.06 and 0.1 g/100 g oil was found to increase as the temperature increased, according to principal component analysis results. Based on its strong lipid oxidation inhibiting capacity, RE can be used as a potential natural extract for stabilizing sunflower oil against oxidation. BEO, at carefully selected concentrations, can be suggested as an alternative supplement of plant origin for improving oil stabilization.

Practical applications: Sunflower oil is a widely used vegetable oil for cooking and frying, and has a high linoleic acid content of about 40–70%. Here we show that sunflower oil can be stabilized by adding rosemary and blackseed extracts. The treatment can be useful especially in applications which require heating the oil to high temperatures.
Generalized linear model describes determinants of total antioxidant capacity of refined vegetable oils
Authors: Castelo‐Branco Vanessa Naciuk , Torres Alexandre Guedes
Published: November 2011

The total antioxidant capacity of edible oils corresponds to the integrated action of antioxidant compounds. The antioxidant capacity may be used as a proxy of the chemical antioxidant activities of components in oils, but this hypothesis has not been tested by multivariate statistical analysis. Tocols, fatty acids, artificial antioxidants, peroxide value, conjugated dienes, and total antioxidant capacity were determined in samples of refined oils of soybean, corn, canola, and sunflower. Generalized linear models and multiple regression models were adjusted to estimate the integrated association between the total antioxidant capacity and chemical components of oils. The generalized linear model of antioxidant capacity better adjusted to the data because the descriptive variable type of oil was a significant predictor. The type of oil, γ‐ and δ‐tocopherols, and peroxide value explained 95% of the variability of antioxidant capacity in the model (p = 0.0006). Besides, γ‐tocopherol was the most important predictor variable for the model considering the p‐value and the estimated relative weight for the model. Therefore, γ‐tocopherol was the major determinant of total antioxidant capacity of refined oils of soybean, corn, canola, and sunflower.

Practical applications: Direct spectrophotometric assay of antioxidant activity can be used to determine the antioxidant quality of fresh refined oils. Furthermore, the statistical evaluation of chemical determinants of vegetable oils based on generalized linear models might contribute to our understanding of the antioxidant quality and the stability of oils.
A Mild Titanium‐Catalyzed Synthesis of Functionalized Amino Coumarins as Fluorescence Labels
Authors: Wirtz Lisa , Kazmaier Uli
Published: November 2011

In contrast to Brønsted and other Lewis acids ClTi(OiPr)3 is especially suited to catalyze the formation of amino‐substituted coumarins from aminophenols and functionalized β‐oxo esters in a Pechmann condensation. This straightforward protocol allows the synthesis of fluorescence labels and false fluorescent neurotransmitters.
Coloured Artefacts Formed by Oxidation of Benzene‐1,2,4‐triol and β‐Dopa During the Extraction of Cortinarius violaceus (Agaricales) with Alcohols
Authors: von Nussbaum Franz , Rüth Matthias , Spiteller Peter , Hübscher‐Weissert Tina , Löbermann Florian , Polborn Kurt , Steglich Wolfgang
Published: November 2011

An array of coloured artefacts was formed upon extraction of the mushroom Cortinarius violaceus with methanol. The structures of these pigments were determined by spectroscopic investigations, including NMR and mass spectrometric analyses. Cortiviolate A and dihydrocortiviol A arise by oxidative dimerization of benzene‐1,2,4‐triol, and cortiviolate B is formed by an unprecedented oxidative rearrangement of β‐dopa. The oxidations are caused by iron(III) ions, released from the iron complex of (R)‐β‐dopa – the native violet pigment of the mushroom. In the course of these investigations, syntheses of the cortiviolates, dihydrocortiviol A, gomphilactone, and two related dilactones were carried out.
Ruthenium‐Catalyzed Sequential Enyne Cross‐Metathesis/ATRA Reactions
Authors: Kiefer Gregor , Ruiz Jesus , Solari Euro , Hilt Gerhard , Severin Kay
Published: November 2011

Sequential enyne cross‐metathesis reactions of arylalkynes with ethylene followed by atom transfer radical addition (ATRA) with ethyl dichloroacetate or dichloroacetonitrile provide 1,5‐dichloropent‐2‐ene derivatives. The second‐generation Grubbs alkylidene complex [RuCl2(=CHPh)(PCy3)(NHC)] [NHC = 1,3‐bis(2,4,6‐trimethylphenyl)‐2‐imidazolidinylidene] is used as the catalyst precursor for both reactions. Preliminary results show that the reaction products can be converted into vinylcyclopropanes by dechlorination with magnesium or manganese.
One‐Pot Conversion of Serine Derivatives and Amino Sugars into Oxazine Derivatives of γ‐Aryl‐γ‐(hydroxy)amines
Authors: Boto Alicia , Gallardo Juan A. , Álvarez Eleuterio
Published: November 2011

A one‐pot process for the transformation of relatively inexpensive serine derivatives into oxazine derivatives of γ‐aryl‐γ‐hydroxy‐α‐amino acids is described. The reaction preferentially afforded 4,6‐cis oxazines. The method can also be applied to the transformation of amino sugars into highly functionalized oxazines, which are precursors of chiral amines.
Convenient Synthesis and Evaluation of a Heptadentate Bifunctional Ligand for Radioimmunotherapy Applications (Eur. J. Org. Chem. 33/2011)
Authors: Chong Hyun‐Soon , Sun Xiang , Dong Pengfei , Kang Chi Soo
Published: November 2011

The cover picture shows the phase contrast image of colon cancer cells (HT29) taken by a confocal microscope as the background image. Bifunctional ligands are an essential component in the biomedical and radiopharmaceutical application of biologically active metals as cytotoxic agents or imaging probes. We herein present the efficient synthesis and evaluation of the bifunctional ligand C‐NE3TA for antibody‐targeted radiation cancer therapy. The synthetic methods to construct the bifunctional ligand are centered on the regiospecific ring opening of aziridine and the aziridinium cation. Details are discussed in the article by H.‐S. Chong et al. on p. 6641 ff.
Loading techniques for OFDM systems with nonlinear distortion effects
Authors: Araújo Teresa , Dinis Rui
Published: November 2011

In this paper, we study the impact of nonlinear distortion effects on adaptive orthogonal frequency division multiplexing systems. An analytical statistical characterisation of the transmitted signals, which is obtained by taking advantage of the Gaussian‐like nature of the orthogonal frequency division multiplexing signals when the number of subcarriers is high, is included. This statistical characterisation is used to evaluate loading algorithms in the presence of strong nonlinear distortion effects and to redefine loading algorithms taking into account nonlinear distortion issues. Copyright © 2011 John Wiley & Sons, Ltd.
Are Analysts' Loss Functions Asymmetric?
Authors: Clatworthy Mark A. , Peel David A. , Pope Peter F.
Published: November 2011

Despite displaying a statistically significant optimism bias, analysts' earnings forecasts are an important input to investors’ valuation models. Understanding the possible reasons for any bias is important if information is to be extracted from earnings forecasts and used optimally by investors. Extant research into the shape of analysts' loss functions explains optimism bias as resulting from analysts minimizing the mean absolute forecast error under symmetric, linear loss functions. When the distribution of earnings outcomes is skewed, optimalforecasts can appear biased. In contrast, research into analysts' economic incentives suggests that positive and negative earnings forecast errors made by analysts are not penalized or rewarded symmetrically, suggesting that asymmetric loss functions are an appropriate characterization. To reconcile these findings, we exploit results from economic theory relating to the Linex loss function to discriminate between the symmetric linear loss and the asymmetric loss explanations of analyst forecast bias. Under asymmetric loss functions optimal forecasts will appear biased even if earnings outcomes are symmetric. Our empirical results support the asymmetric loss function explanation. Further analysis also reveals that forecast bias varies systematically across firm characteristics that capture systematic variation in the earnings forecast error distribution. Copyright © 2011 John Wiley & Sons, Ltd.
Space‐Time Model versus VAR Model: Forecasting Electricity demand in Japan
Authors: Ohtsuka Yoshihiro , Kakamu Kazuhiko
Published: November 2011

This paper examined the forecasting performance of disaggregated data with spatial dependency and applied it to forecasting electricity demand in Japan. We compared the performance of the spatial autoregressive ARMA (SAR‐ARMA) model with that of the vector autoregressive (VAR) model from a Bayesian perspective. With regard to the log marginal likelihood and log predictive density, the VAR(1) model performed better than the SAR‐ARMA( 1,1) model. In the case of electricity demand in Japan, we can conclude that the VAR model with contemporaneous aggregation had better forecasting performance than the SAR‐ARMA model. Copyright © 2011 John Wiley & Sons, Ltd.
Identification of a microglia phenotype supportive of remyelination
Authors: Olah Marta , Amor Sandra , Brouwer Nieske , Vinet Jonathan , Eggen Bart , Biber Knut , Boddeke Hendrikus W. G. M.
Published: November 2011

In multiple sclerosis, endogenous oligodendrocyte precursor cells (OPCs) attempt to remyelinate areas of myelin damage. During disease progression, however, these attempts fail. It has been suggested that modulating the inflammatory environment of the lesion might provide a promising therapeutic approach to promote endogenous remyelination. Microglia are known to play a central role in neuroinflammatory processes. To investigate the microglia phenotype that supports remyelination, we performed genome‐wide gene expression analysis of microglia from the corpus callosum during demyelination and remyelination in the mouse cuprizone model, in which remyelination spontaneously occurs after an episode of toxin‐induced primary demyelination. We provide evidence for the existence of a microglia phenotype that supports remyelination already at the onset of demyelination and persists throughout the remyelination process. Our data show that microglia are involved in the phagocytosis of myelin debris and apoptotic cells during demyelination. Furthermore, they express a cytokine and chemokine repertoire enabling them to activate and recruit endogenous OPCs to the lesion site and deliver trophic support during remyelination. This study not only provides a detailed transcriptomic analysis of the remyelination‐supportive microglia phenotype but also reinforces the notion that the primary function of microglia is the maintenance of tissue homeostasis and the support of regeneration already at the earliest stages in the development of demyelinating lesions. © 2011 Wiley Periodicals, Inc.
A systematic review of the accuracy and clinical utility of the Addenbrooke's Cognitive Examination and the Addenbrooke's Cognitive Examination—Revised in the diagnosis of dementia
Authors: Crawford Stephanie , Whitnall Leigh , Robertson Joanne , Evans Jonathan J.
Published: November 2011

Objectives

To review the evidence relating to the diagnostic accuracy and clinical utility of the Addenbrooke's Cognitive Examination (ACE) and its updated version, the Addenbrooke's Cognitive Examination—Revised (ACE‐R) in relation to the diagnosis of dementia.

Design

A systematic search of relevant databases was conducted, covering the period 2000 to April 2010. Specific journals and reference lists were hand searched. Identified studies that fulfilled the inclusion criteria were reviewed using a tailored, methodological quality rating checklist.

Results

The systematic search process identified nine studies for review (seven relating to the ACE, two on the ACE‐R). Strengths and weaknesses across studies are considered, and diagnostic accuracy measures are presented for six out of the nine studies.

Conclusion

The evidence suggests that the ACE/ACE‐R is capable of providing information on a range of cognitive domains and of differentiating well between those with and those without cognitive impairment. Further research examining how the tools distinguish between dementia subtypes and mild cognitive impairment will further benefit the evidence base. Copyright © 2011 John Wiley & Sons, Ltd.
Eddy correlations for water flow in a single fracture with abruptly changing aperture
Authors: Qian Jiazhong , Liang Min , Chen Zhou , Zhan Hongbin
Published: November 2011

Fluid flow in single fractures with non‐uniform apertures is an important research subject in many disciplines. The abruptly changing aperture is a special case of such non‐uniformity. This paper simulates water flow in a single fracture with abruptly changing aperture (SF‐ACA) using the Lattice Boltzmann Method (LBM) and the Finite Volume Method (FVM). The flow occurs with the Reynolds number (Re) ranging from 5 to 900 and a ratio of aperture change (E) of 3 (E = D/d, where D and d are the larger and smaller apertures, respectively). For Re values between 5 and 100, both LBM and FVM can successfully simulate the eddy development in the expansion regime of an SF‐ACA. Flow with high Re values (up to 900) is simulated by FVM, which appears to be numerically more stable than LBM for high‐Re flow problems studied here. The flow symmetry in the expansion regime breaks at the Re value between 400 and 500. Our simulation result shows a linear relationship between l1/d and Re at low Re (5–100) or higher Re (110–900) values, where defined as the length from the location of abrupt expansion to the right edge of the first eddy along the flow direction. If considering the simulation results for the entire simulated range of Re (5–900), the l1/d–Re relationship is better described by a non‐linear logarithmical function. The l1/d approaches an asymptotic constant at large Re. Copyright © 2011 John Wiley & Sons, Ltd.
Height loss predicts subsequent hip fracture in men and women of the Framingham Study
Authors: Hannan Marian T , Broe Kerry E , Cupples L Adrienne , Dufour Alyssa B , Rockwell Margo , Kiel Douglas P
Published: November 2011

Although height is a risk factor for osteoporotic fracture, current risk assessments do not consider height loss. Height loss may be a simple measurement that clinicians could use to predict fracture or need for further testing. The objective was to examine height loss and subsequent hip fracture, evaluating both long-term adult height loss and recent height loss. Prospective cohort of 3081 adults from the Framingham Heart Study. Height was measured biennially since 1948, and cohort followed for hip fracture through 2005. Adult height loss from middle-age years across 24 years and recent height loss in elderly years were considered. Cox proportional hazard regression was used to estimate association between height loss and risk of hip fracture. Of 1297 men and 1784 women, mean baseline age was 66 years (SD = 7.8). Average height loss for men was 1.06 inches (0.76), and for women was 1.12 inches (0.84). A total of 11% of men and 15% of women lost ≥2 inches of height. Mean follow-up was 17 years, during which 71 men and 278 women had incident hip fractures. For each 1-inch of height loss, hazard ratio (HR) = 1.4 in men [95% confidence interval (CI): 1.00, 1.99], and 1.04 in women (95% CI: 0.88, 1.23). Men and women who lost ≥2 inches of height had increased fracture risk (compared with 0 to <2 inches) of borderline significance: men HR = 1.8, 95% CI: 0.86, 3.61; women HR = 1.3, 95% CI: 0.90, 1.76. Recent height loss in elders significantly increased the risk of hip fracture, 54% in men and 21% in women (95% CI: 1.14, 2.09; 1.03, 1.42, respectively). Adult height loss predicted hip fracture risk in men in our study. Recent height loss in elderly men and women predicted risk of hip fracture. © 2012 American Society for Bone and Mineral Research
Height loss in older women: Risk of hip fracture and mortality independent of vertebral fractures
Authors: Hillier Teresa A , Lui Li-Yung , Kado Deborah M , LeBlanc ES , Vesco Kimberly K , Bauer Douglas C , Cauley Jane A , Ensrud Kristine E , Black Dennis M , Hochberg Marc C , Cummings Steven R
Published: November 2011

We examined if height loss in older women predicts risk of hip fractures, other nonspine fractures, and mortality, and whether this risk is independent of both vertebral fractures (VFx) and bone mineral density (BMD) by dual-energy X-ray absorptiometry. Among 3124 women age 65 and older in the Study of Osteoporotic Fractures, we assessed the association with measured height change between year 0 (1986–1988) and year 15 (2002–2004) and subsequent risk of radiologically confirmed hip fractures, other nonspine fractures, and mortality assessed via death certificates. Follow-up occurred every 4 months for fractures and vital status (>95% contacts complete). Cox proportional hazards models assessed risk of hip fracture, nonspine fracture, and mortality over a mean of 5 years after height change was assessed (ie, after final height measurement). After adjustment for VFx, BMD, and other potential covariates, height loss >5 cm was associated with a marked increased risk of hip fracture [hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.06, 2.12], nonspine fracture (HR 1.48; 95% CI 1.20, 1.83), and mortality (1.45; 95% CI 1.21, 1.73). Although primary analyses were a subset of 3124 survivors healthy enough to return for a year 15 height measurement, a sensitivity analysis in the entire cohort (n = 9677) using initial height in earlier adulthood [self-reported height at age 25 (−40 years) to measured height age >65 years (Year 0)] demonstrated consistent results. Height loss >5 cm (2″) in older women was associated with a nearly 50% increased risk of hip fracture, nonspine fracture, and mortality—independent of incident VFx and BMD. © 2012 American Society for Bone and Mineral Research
RANK-dependent autosomal recessive osteopetrosis: Characterization of five new cases with novel mutations
Authors: Pangrazio Alessandra , Cassani Barbara , Guerrini Matteo M , Crockett Julie C , Marrella Veronica , Zammataro Luca , Strina Dario , Schulz Ansgar , Schlack Claire , Kornak Uwe , Mellis David J , Duthie Angela , Helfrich Miep H , Durandy Anne , Moshous Despina , Vellodi Ashok , Chiesa Robert , Veys Paul , Lo Iacono Nadia , Vezzoni Paolo , Fischer Alain , Villa Anna , Sobacchi Cristina
Published: November 2011

Autosomal recessive osteopetrosis (ARO) is a genetically heterogeneous disorder attributed to reduced bone resorption by osteoclasts. Most human AROs are classified as osteoclast rich, but recently two subsets of osteoclast-poor ARO have been recognized as caused by defects in either TNFSF11 or TNFRSF11A genes, coding the RANKL and RANK proteins, respectively. The RANKL/RANK axis drives osteoclast differentiation and also plays a role in the immune system. In fact, we have recently reported that mutations in the TNFRSF11A gene lead to osteoclast-poor osteopetrosis associated with hypogammaglobulinemia. Here we present the characterization of five additional unpublished patients from four unrelated families in which we found five novel mutations in the TNFRSF11A gene, including two missense and two nonsense mutations and a single-nucleotide insertion. Immunological investigation in three of them showed that the previously described defect in the B cell compartment was present only in some patients and that its severity seemed to increase with age and the progression of the disease. HSCT performed in all five patients almost completely cured the disease even when carried out in late infancy. Hypercalcemia was the most important posttransplant complication. Overall, our results further underline the heterogeneity of human ARO also deriving from the interplay between bone and the immune system, and highlight the prognostic and therapeutic implications of the molecular diagnosis. © 2012 American Society for Bone and Mineral Research
Reduced cortical bone compositional heterogeneity with bisphosphonate treatment in postmenopausal women with intertrochanteric and subtrochanteric fractures
Authors: Donnelly Eve , Meredith Dennis S , Nguyen Joseph T , Gladnick Brian P , Rebolledo Brian J , Shaffer Andre D , Lorich Dean G , Lane Joseph M , Boskey Adele L
Published: November 2011

Reduction of bone turnover with bisphosphonate treatment alters bone mineral and matrix properties. Our objective was to investigate the effect of bisphosphonate treatment on bone tissue properties near fragility fracture sites in the proximal femur in postmenopausal women with osteoporosis. The mineral and collagen properties of corticocancellous biopsies from the proximal femur were compared in bisphosphonate-naive (−BIS, n = 20) and bisphosphonate-treated (+BIS, n = 20, duration 7 ± 5 years) patients with intertrochanteric (IT) and subtrochanteric (ST) fractures using Fourier transform infrared imaging (FTIRI). The mean values of the FTIRI parameter distributions were similar across groups, but the widths of the parameter distributions tended to be reduced in the +BIS group relative to the −BIS group. Specifically, the widths of the cortical collagen maturity and crystallinity were reduced in the +BIS group relative to those of the −BIS group by 28% (+BIS 0.45 ± 0.18 versus −BIS 0.63 ± 0.28, p = 0.03) and 17% (+BIS 0.087 ± 0.012 versus −BIS 0.104 ± 0.036, p = 0.05), respectively. When the tissue properties were examined as a function of fracture morphology within the +BIS group, the FTIR parameters were generally similar regardless of fracture morphology. However, the cortical mineral:matrix ratio was 8% greater in tissue from patients with atypical ST fractures (n = 6) than that of patients with typical (IT or spiral ST) fractures (n = 14) (Atypical 5.6 ± 0.3 versus Typical 5.2 ± 0.5, p = 0.03). Thus, although the mean values of the FTIR properties were similar in both groups, the tissue in bisphosphonate-treated patients had a more uniform composition than that of bisphosphonate-naive patients. The observed reductions in mineral and matrix heterogeneity may diminish tissue-level toughening mechanisms. © 2012 American Society for Bone and Mineral Research
Interactions between extracellular signal-regulated kinase 1/2 and P38 Map kinase pathways in the control of RUNX2 phosphorylation and transcriptional activity
Authors: Ge Chunxi , Yang Qian , Zhao Guisheng , Yu Hong , Kirkwood Keith L , Franceschi Renny T
Published: November 2011

RUNX2, a key transcription factor for osteoblast differentiation, is regulated by ERK1/2 and p38 MAP kinase-mediated phosphorylation. However, the specific contribution of each kinase to RUNX2-dependent transcription is not known. Here we investigate ERK and p38 regulation of RUNX2 using a unique P-RUNX2-specific antibody. Both MAP kinases stimulated RUNX2 Ser319 phosphorylation and transcriptional activity. However, a clear preference for ERK1 versus p38α/β was found when the ability of these MAPKs to phosphorylate and activate RUNX2 was compared. Similarly, ERK1 preferentially bound to a consensus MAPK binding site on RUNX2 that was essential for the activity of either kinase. To assess the relative contribution of ERK1/2 and p38 to osteoblast gene expression, MC3T3-E1 preosteoblast cells were grown in control or ascorbic acid (AA)-containing medium ± BMP2/7. AA-induced gene expression, which requires collagen matrix synthesis, was associated with parallel increases in P-ERK and RUNX2-S319-P in the absence of any changes in P-p38. This response was blocked by ERK, but not p38, inhibition. Significantly, in the presence of AA, BMP2/7 synergistically stimulated RUNX2 S319 phosphorylation and transcriptional activity without affecting total RUNX2 and this response was totally dependent on ERK/MAPK activity. In contrast, although p38 inhibition partially blocked BMP-dependent transcription, it did not affect RUNX2 S319 phosphorylation, suggesting the involvement of other phosphorylation sites and/or transcription factors in this response. Based on this work, we conclude that extracellular matrix and BMP regulation of RUNX2 phosphorylation and transcriptional activity in osteoblasts is predominantly mediated by ERK rather than p38 MAPKs. © 2012 American Society for Bone and Mineral Research.
Individual trabecula segmentation (ITS)-based morphological analyses and microfinite element analysis of HR-pQCT images discriminate postmenopausal fragility fractures independent of DXA measurements
Authors: Liu X Sherry , Stein Emily M , Zhou Bin , Zhang Chiyuan A , Nickolas Thomas L , Cohen Adi , Thomas Valerie , McMahon Donald J , Cosman Felicia , Nieves Jeri , Shane Elizabeth , Guo X Edward
Published: November 2011

Osteoporosis is typically diagnosed by dual-energy X-ray absorptiometry (DXA) measurements of areal bone mineral density (aBMD). Emerging technologies, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), may increase the diagnostic accuracy of DXA and enhance our mechanistic understanding of decreased bone strength in osteoporosis. Women with (n = 68) and without (n = 101) a history of postmenopausal fragility fracture had aBMD measured by DXA, trabecular plate and rod microarchitecture measured by HR-pQCT image-based individual trabecula segmentation (ITS) analysis, and whole bone and trabecular bone stiffness by microfinite element analysis (µFEA) of HR-pQCT images at the radius and tibia. DXA T-scores were similar in women with and without fractures at the spine, hip, and 1/3 radius, but lower in fracture subjects at the ultradistal radius. Trabecular microarchitecture of fracture subjects was characterized by preferential reductions in trabecular plate bone volume, number, and connectivity over rod trabecular parameters, loss of axially aligned trabeculae, and a more rod-like trabecular network. In addition, decreased thickness and size of trabecular plates were observed at the tibia. The differences between groups were greater at the radius than the tibia for plate number, rod bone volume fraction and number, and plate–rod and rod–rod junction densities. Most differences between groups remained after adjustment for T-score by DXA. At a fixed bone volume fraction, trabecular plate volume, number, and connectivity were directly associated with bone stiffness. In contrast, rod volume, number, and connectivity were inversely associated with bone stiffness. In summary, HR-pQCT-based ITS and µFEA measurements discriminate fracture status in postmenopausal women independent of DXA measurements. Moreover, these results suggest that preferential loss of plate-like trabeculae contribute to lower trabecular bone and whole bone stiffness in women with fractures. We conclude that HR-pQCT-based ITS and µFEA measurements increase our understanding of the microstructural pathogenesis of fragility fracture in postmenopausal women. © 2012 American Society for Bone and Mineral Research
Genome-wide association of an integrated osteoporosis-related phenotype: Is there evidence for pleiotropic genes?
Authors: Karasik David , Cheung Ching Lung , Zhou Yanhua , Cupples L Adrienne , Kiel Douglas P , Demissie Serkalem
Published: November 2011

Multiple musculoskeletal traits assessed by various methods at different skeletal sites serve as surrogates for osteoporosis risk. However, it is a challenge to select the most relevant phenotypes for genetic study of fractures. Principal component analyses (PCA) were conducted in participants of the Framingham Osteoporosis Study on 17 measures including bond mineral density (BMD) (hip and spine), heel ultrasound, leg lean mass (LLM), and hip geometric indices, adjusting for covariates (age, height, body mass index [BMI]), in a combined sample of 1180 men and 1758 women, as well as in each sex. Four principal components (PCs) jointly explained ∼69% of the total variability of musculoskeletal traits. PC1, explaining ∼33% of the total variance, was referred to as the component of “Bone strength,” because it included the hip and spine BMD as well as several hip cross-sectional properties. PC2 (20.5% variance) was labeled as “Femoral cross-sectional geometry;” PC3 (∼8% variance) captured only ultrasound measures; PC4, explaining ∼7% variance, was correlated with LLM and hip geometry. We then evaluated ∼2.5 mil SNPs for association with PCs 1, 2, and 4. There were genome-wide significant associations (p < 5 × 10−8) between PC2 and HTR1E (that codes for one of the serotonin receptors) and PC4 with COL4A2 in women. In the sexes-combined sample, AKAP6 was associated with PC2 (p = 1.40 × 10−7). A single nucleotide polymorphism (SNP) in HTR1E was also associated with the risk of nonvertebral fractures in women (p = 0.005). Functions of top associated genes were enriched for the skeletal and muscular system development (p < 0.05). In conclusion, multivariate combination provides genetic associations not identified in the analysis of primary phenotypes. Genome-wide screening for the linear combinations of multiple osteoporosis-related phenotypes suggests that there are variants with potentially pleiotropic effects in established and novel pathways to be followed up to provide further evidence of their functions. © 2012 American Society for Bone and Mineral Research
The Italian registry of therapeutic apheresis: Granulocyte–monocyte apheresis in the treatment of inflammatory bowel disease. A multicentric study
Authors: Passalacqua Stefano , Ferraro Pietro Manuel , Bresci Giampaolo , D'Ovidio Valeria , Astegiano Marco , Principi Mariabeatrice , Testa Roberto , D'Incà Renata , Valpiani Daniela , Armuzzi Alessandro , Sablich Renato , Cavallaro Flaminia , Costa Francesco , Di Leo Vincenza , Colombo Elisabetta , Santini Alessia , Aratari Annalisa , Lecis Pierenrico , Saladino Valeria , Riegler Gabriele , Marco Marino , Calella Francesca , Ricci Chiara , Guidi Maria Luisa , Repaci Giuseppe , Silla Michele
Published: November 2011

Leukocytes are thought to play an important role in the pathogenesis of inflammatory bowel diseases; granulocyte–monocyte adsorptive (GMA) apheresis, an extracorporeal technique aimed at removing activated circulating leukocytes from the blood, may represent a safe and effective therapeutic tool in these patients. The Italian Registry of Therapeutic Apheresis performed an observational, multicentric study involving 24 Gastroenterology Units. In this study, laboratory data and clinical outcomes of 230 patients (148 males, mean age 43.5 years) affected with ulcerative colitis (UC, n = 194) or Crohn's disease (CD, n = 36) who underwent one or more cycles of GMA were analyzed. Each cycle consisted of five GMA treatments. The patients were followed up for a mean of 8.7 (min. 3 to max. 12) months. At 3 months, positive outcome was achieved in 77.7% of UC patients (72.0% remission, 5.7% clinical response) and 61.3% of CD patients (54.8% remission, 6.5% clinical response). The cumulative proportion of positive outcome at 12 months was 87.1% for UC patients (83.7% remission, 3.4% clinical response) and 77.4% for CD patients (74.2% remission, 3.2% clinical response). No single clinical or laboratory parameter among those analyzed (age, sex, disease characteristics, history of smoking, medication history, baseline values of clinical activity index (CAI)/Crohn's disease activity index (CDAI), hemoglobin, white blood cells count, and erythrocyte sedimentation rate) was independently associated with clinical outcome. The procedure was well tolerated with no significant adverse effects registered. © 2011 Wiley Periodicals, Inc.
Lenograstim with or without dexamethasone for neutrophil mobilization in healthy donors: Short‐term kinetics of white blood cells and effects of granulocyte apheresis
Authors: Kessler Kian , Goudeva Lilia , Heuft Hans‐Gert
Published: November 2011

Objectives: To determine the optimal time schedule for neutrophil collection after single mobilization with glycosylated recombinant granulocyte colony‐stimulating factor (G‐CSF, lenograstim) with or without dexamethasone (DXM). Donors and Methods: In this prospective randomized trial, 26 healthy volunteers were randomly assigned to a single subcutaneous dose of lenograstim 6 μg/kg plus 8‐mg DXM (G‐CSF/DXM, n = 13) or placebo (G‐CSF/placebo, n = 13). Hematological and biochemical parameters were analyzed before and 12, 15, 18, 21, 24, 27, 29, 36, 48, 60, 72, and 84 h and 7 and 30 days after mobilization. Six G‐CSF/DXM subjects underwent standard neutrophil apheresis (NA) 12 and 36 h after mobilization. Results: Polymorphonuclear neutrophil (PMN) counts 12 and 21 h after mobilization were 22.7 (16.6−32.8) × 109/L and 22.4 (18.6−30.6) × 109/L for G‐CSF/placebo versus 33.1 (24.2–44.9) × 109/L and 32.5 (17.4–39.6) × 109/L for G‐CSF/DXM. This mobilization plateau was followed by slow normalization at 72–84 h. The six NA subjects had median PMN yields of 62 (47–101) × 109 and 39 (23–42) × 109 per therapeutic unit. After the first apheresis, PMN counts sharply decreased to 21.1 (14.8–26.3) × 109/L and then temporarily recovered to 25.9 (18.9–36.5) × 109/L (P ≤ 0.001) over the next 8 h. Conclusions: Single doses of lenograstim with or without DXM induced a PMN plateau that lasted 9 h (12–21 h after mobilization), with PMN counts suitable for neutrophil collection. Lenograstim plus DXM made it possible to perform NA twice, 12 and 36 h after mobilization. © 2011 Wiley Periodicals, Inc.
Dissolved phosphorus composition of grassland leachates following application of dairy‐slurry size fractions
Authors: Fuentes Bárbara , Dixon Elizabeth , de la Luz Mora María , Turner Benjamin L. , Bol Roland
Published: November 2011

Appropriate management of P from slurry can increase crop production and decrease nutrient loss to water bodies. The present study examined how the application of different size fractions of dairy slurry influenced the quantity and composition of P leached from grassland in a temperate climate. Soil blocks were amended (day 0 = start of the experiment) with either whole slurry (WS), the > 425 μm fraction (coarse slurry fraction, CSF), the < 45 μm slurry fraction (fine liquid slurry fraction, FLF), or not amended, i.e., the control soil (CON). Deionized water was added to the soil blocks to simulate six sequential rainfall events, equivalent to 250 mm (day 0.2, 1.2, 4.2, 11.2) or 500 mm of rainfall (day 18.2 and 25.2), with leachates collected the following day. The results showed that total dissolved P (TDP), dissolved reactive P (DRP), dissolved unreactive P (DUP), orthophosphate, phosphomonoester, and pyrophosphate concentrations generally decreased with the increasing number of simulated rain events. Total dissolved P was leached in the following order WS > FLF ≈ CSF > CON. Dissolved organic C was correlated with TDP, DRP, and DUP in leachates of all treatments. The highest concentrations of dissolved phosphomonoesters and pyrophosphate (147 μg P L–1 and 57 μg P L–1, respectively) were detected using solution 31P‐NMR spectroscopy in the WS leachates. Overall, there were significant differences observed between slurry treatments (e.g., relative contributions of inorganic P vs. organic P of dissolved P in leachates). Differences were independent from the rate at which slurry P was applied, because the highest dissolved P losses per unit of slurry P applied were measured in the FLF, i.e., the treatment that received the smallest amount of P. We conclude that the specific particle‐size composition of applied slurry influences dissolved P losses from grassland systems. This information should be taken in account in farm‐management approaches which aim to minimizing dissolved slurry P losses from grassland systems.
Difference in response to aluminum stress among Tibetan wild barley genotypes
Authors: Dai Huaxin , Shan Wunian , Zhao Jing , Zhang Guoping , Li Chengdao , Wu Feibo
Published: November 2011

Wild barley (Hordeum sp.) germplasm is rich in genetic diversity and provides a treasure trove of useful genes for crop improvement. We carried out a comprehensive program combining short‐term hydroponic screening via hematoxylin‐staining of root‐regrowth procedure and filter paper–based evaluation of diverse germplasm in response to Al/acid stress using 105 annual Tibetan wild barley and 45 cultivated barley genotypes. Root elongation among the 105 Tibetan wild barley genotypes varied significantly after Al exposure, ranging from 62.9% to 80.0% in variation coefficients and 4.35 to 4.45 in diversity index. These genotypic differences in Al resistance were fairly consistent in both the hydroponic and filter paper–based evaluations: XZ16, XZ166, and XZ113 were selected as Al‐resistant genotypes, and XZ61, XZ45, and XZ98 as Al‐sensitive wild genotypes. Furthermore, significantly lower Al concentrations in roots and shoots were detected in the three selected Al‐resistant genotypes than in the three sensitive genotypes in the filter paper–based experiment. Meanwhile, XZ16 was the least affected by Al toxicity in regard to reduced SPAD value (chlorophyll meter readings), plant height, root length, dry biomass, tillers per plant, and chlorophyll fluorescence (Fv/Fm) in the long‐term hydroponic experiment compared with the Al‐resistant cultivated barley cv. Dayton, while XZ61 had the severest stress symptoms.
Residual stress field determination in welds by means of X‐ray, synchrotron and neutron diffraction
Authors: Farajian M. , Nitschke‐Pagel T. , Wimpory R. C. , Hofmann M. , Klaus M.
Published: November 2011

To what extent the welding residual stresses influence fatigue is still unclear and matter of debate. An important reason for this lack of clarity is that the exact determination of residual stress fields in welds is complicated which leads to conservative assumptions about these stresses in the fatigue design codes. The advances in the diffraction analysis of materials offer the opportunity for the full‐field residual strain mapping in welds albeit at the cost of time and technical complexity. In this work residual stress field determination in welded S1100QL specimens by means of the x‐ray, synchrotron and neutron diffraction techniques was undertaken. The results revealed that the maximum values of surface residual stresses are not as frequently assumed, as high as the yield strength in small scale specimens. At the weld toe which could serve as a fatigue crack initiation site, even lower residual stresses than the weld centreline could be present. The in‐depth measurements revealed that the effective part of the residual stress field which could be decisive for the fatigue failure initiation is concentrated at the surface of the weld.
An experimental study of water absorption in polyester composites reinforced with macambira natural fiber
Authors: Cruz V. C. A. , Nóbrega M. M. S. , Silva W. P. da , de Carvalho L. H. , de Lima A. G. B.
Published: November 2011

The use of raw materials from renewable sources, such as vegetable fibers, for example, has been the subject of several studies and researches. One major disadvantage in the use of vegetable fibers in polymer composites is their hydrophilic nature which provides weak interfacial adhesion in polymer‐fiber composites. Due to its importance, the purpose of this paper is to present an experimental study of water absorption in unsaturated polyester composites reinforced with macambira natural fiber. The studied samples have weight composition 30% macambira fiber and 70% unsaturated polyester, with dimensions of 20×20×3 mm3 and 20×20×6 mm3. Tests for water absorption were performed by immersing the samples in a bath of distilled water at 25, 50 and 70°C, and water uptake was measured gravimetrically along the process. Results of the micrographs (SEM), moisture content and area / volume relationships of the composites are shown and analyzed.
A study on diffusion bonding of steel and copper alloy
Authors: Lee H.‐S. , Yoon J.‐H. , Yoo J.‐T. , Yi Y.‐M.
Published: November 2011

In combustion chamber of liquid propellant launch vehicle, the inner shell of the chamber is copper alloy with cooling channels for regenerative cooling and outer shell is steel to maintain high pressure inside the chamber. The purpose of this study is to find the optimum condition for diffusion bonding of copper and steel and the experimental conditions were 3 different pressures at temperatures from 800°C to 950°C. In order to characterize the flow strength of materials at high temperatures, several tensile tests were performed at several temperatures from 800°C to 950°C. This information is used to estimate the test condition for diffusion bonding and superplastic forming. Mechanical properties of bonded specimen were evaluated with single lap joint tests and shear tests. Microstructure of bonded layer has been also observed with SEM with EDX. It is shown that the optimum condition of diffusion bonding is 7 MPa at 890°C, for one hour. Pressurization test of bonded specimen with cooling channels was performed with hydraulic pressure of 87 MPa without failure.