bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of the incorporation of hydroxy‐terminated liquid silicones on the cure characteristics, morphology, and release of a model protein from silicone elastomer‐covered rods
Authors: McConville Christopher , Andrews Gavin P. , David Woolfson A. , Karl Malcolm R.
Published: October 2011

Silicone elastomer systems have previously been shown to offer potential for the sustained release of protein therapeutics. However, the general requirement for the incorporation of large amounts of release enhancing solid excipients to achieve therapeutically effective release rates from these otherwise hydrophobic polymer systems can detrimentally affect the viscosity of the precure silicone elastomer mixture and its curing characteristics. The increase in viscosity necessitates the use of higher operating pressures in manufacture, resulting in higher shear stresses that are often detrimental to the structural integrity of the incorporated protein. The addition of liquid silicones increases the initial tan δ value and the tan δ values in the early stages of curing by increasing the liquid character (G″) of the silicone elastomer system and reducing its elastic character (G′), thereby reducing the shear stress placed on the formulation during manufacture and minimizing the potential for protein degradation. However, SEM analysis has demonstrated that if the liquid character of the silicone elastomer is too high, the formulation will be unable to fill the mold during manufacture. This study demonstrates that incorporation of liquid hydroxy‐terminated polydimethylsiloxanes into addition‐cure silicone elastomer‐covered rod formulations can both effectively lower the viscosity of the precured silicone elastomer and enhance the release rate of the model therapeutic protein bovine serum albumin. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Mesoscopic simulation of the surface inducing effects on the compatibility of PS‐b‐PMMA copolymers
Authors: Mu Dan , Li Jian‐Quan , Wang Song
Published: October 2011

The phase morphologies of designed polystyrene‐block‐poly(methyl methacrylate) (PS‐b‐PMMA) copolymers were studied at 383, 413, and 443 K by mesoscopic simulations. Eighteen patterned surfaces of four series were designed and designated as “ci,” “co,” “gra,” and “rg” to study their influence on changing the microscopic phase morphology of copolymers. The topography of the “ci” series surfaces was shaped by semicircular balls. Different radii were applied to simulate different degrees of surface roughness. The “co” series were composed of cubic columns as the mask, and the cubic columns were separated by equal spaces. Various sizes and heights of columns were used to simulate different degrees of surface roughness. The “gra” series were composed of surfaces with different areas of section and the same height to simulate different degrees of surface roughness. The “rg” series were composed of concentric cuboids with continuous increasing heights and sizes. The degree of phase separation depended on the structures of copolymers, the topography of surfaces and the simulation temperatures. When the triblock copolymer with surfaces induced was composed of the same component at both ends and had larger PS segment percentage, it would present higher values of order parameter, that was, “ABA” showed the highest, “AB” the second high and “BAB” the last, the values of order parameter of the long chains were higher than those of the short ones, except the situation with co‐4432 and co‐8832 surfaces induced. However, the co‐4432 and co‐8832 surfaces performed the most intensive extent of inducing effect. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Development and characterization of thermosensitive hydrogels based on poly(N‐isopropylacrylamide) and calcium alginate
Authors: Petrusic Stojanka , Lewandowski Maryline , Giraud Stéphane , Jovancic Petar , Bugarski Branko , Ostojic Sanja , Koncar Vladan
Published: October 2011

This work refers to the synthesis and characterization of thermosensitive hydrogels based on interpenetrating polymer networks (IPNs) of poly(N‐isopropylacrylamide) (PNIPAAm) and calcium alginate in the form of films. The influence of the crosslinking degree of PNIPAAm and alginate content on thermal, swelling, mechanical, and morphological properties of hydrogels is investigated in detail. Characterization of pure PNIPAAm hydrogels and IPN hydrogels was performed by FTIR, DSC, DMA, and SEM. In addition, the studies of equilibrium swelling behavior as well as swelling, deswelling, and reswelling kinetics are performed. The results obtained imply the benefits of synthesizing IPNs based on PNIPAAm and calcium alginate over pure PNIPAAm hydrogels. The presence of calcium alginate contributes to the improvement of mechanical properties, the deswelling rate of hydrogels, and the network porosity, without altering the thermosensitivity of PNIPAAm significantly. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Myositis‐specific anti‐155/140 autoantibodies target transcription intermediary factor 1 family proteins
Authors: Fujimoto Manabu , Hamaguchi Yasuhito , Kaji Kenzo , Matsushita Takashi , Ichimura Yuki , Kodera Masanari , Ishiguro Naoko , Ueda‐Hayakawa Ikuko , Asano Yoshihide , Ogawa Fumihide , Fujikawa Keita , Miyagi Takuya , Mabuchi Eriko , Hirose Kenji , Akimoto Narihiro , Hatta Naohito , Tsutsui Kiyohiro , Higashi Akira , Igarashi Atsuyuki , Seishima Mariko , Hasegawa Minoru , Takehara Kazuhiko
Published: October 2011

Objective

To identify the 140‐kd autoantigen recognized by anti‐155/140 autoantibodies that are associated with adult cancer‐associated dermatomyositis (DM) and juvenile DM and to determine the clinical relevance of anti‐155/140 antibodies in a large cohort.

Methods

Sera from 456 DM patients were assessed for the presence of anti‐155/140 antibodies by immunoprecipitation using K562 cell extracts as substrate. Using immunoprecipitation and Western blotting, we then examined whether anti‐155/140–positive sera recognized transcription intermediary factor 1α (TIF‐1α), TIF‐1β, and TIF‐1γ. The clinical associations of antigen reactivity were also evaluated.

Results

Anti‐155/140–positive sera reacted with 140‐kd TIF‐1α in addition to 155‐kd TIF‐1γ. Among sera from 456 DM patients, 52 were reactive with both TIF‐1α and TIF‐1γ, while another 25 were reactive with TIF‐1γ alone. Additionally, 7 were reactive with TIF‐1β. Malignancy was more frequently found in adult patients with both anti–TIF‐1α and anti–TIF‐1γ antibodies than in those with anti–TIF‐1γ antibodies alone (73% versus 50%; P < 0.05). In addition to juvenile DM patients and middle‐aged and older DM patients with high percentages of malignancy, 8 “young adult” DM patients without malignancy had these autoantibodies.

Conclusion

Anti‐155/140 antibodies target TIF‐1 family proteins, TIF‐1α and TIF‐1β, in addition to TIF‐1γ. Since TIF‐1 proteins have significant roles in oncogenesis, these antibodies may be produced during misdirected antitumor immunity.
Training Employment Acquisition Skills for Adolescents with a Substance Abuse History
Authors: Taylor Sarah Ann , Mudford Oliver C. , Phillips Katrina J.
Published: October 2011

Obtaining paid employment is beneficial for youth during and following treatment for substance abuse. A training program for acquiring employment was implemented at a residential drug and alcohol rehabilitation facility for nine residents who were near to completing the program. Data are presented from three residents with the most complete data sets. Skills training was provided for completing biographic information on job application forms, job searching by telephone and in person, and job interviews. The training process included behavioral procedures of providing instructions, modeling, role‐play, and feedback. Improvements were demonstrated across all behaviors and participants after the training and generalized to real community materials and settings. All participants who remained in treatment also gained real work experience opportunities or regular paid employment. Copyright © 2011 John Wiley & Sons, Ltd.
Der altruistische Golden Gate‐Egel und das ITIS‐Projekt
Authors: Kutschera Ulrich
Published: October 2011

Vor 25 Jahren wurde im Stow Lake des Stadtparks von San Francisco, Kalifornien (USA), eine Egelart entdeckt und beschrieben. Dieser Brutpflege betreibende “Golden Gate‐Leech” konnte inzwischen auch auf Grundlage von DNA‐Sequenz‐Analysen als neue Art identifiziert werden. In den Vereinigten Staaten gibt es ein offizielles Integrated Taxonomic Information System (ITIS), in dem diese endemische Egelart gelistet wird. Ein derartiges zentrales Biodiversitäts‐Register fehlt in Deutschland.
How Important Is Backbonding in Metal Complexes Containing N‐Heterocyclic Carbenes? Structural and NBO Analysis
Authors: Comas‐Vives Aleix , Harvey Jeremy N.
Published: October 2011

DFT calculations have been used to analyze the degree of metal‐to‐ligand backbonding in a range of model transition metal complexes of N‐heterocyclic carbenes. Two new methods of analysis have been introduced for this purpose. The first is structural and involves comparing the variation of the C–N bond length and N–C–N angle in complexes in which σ‐donation is dominant (e.g. complexes with BF3) and others in which backbonding might be expected. The second uses the perturbative natural bonding orbital (NBO) method. Both methods lead to the firm conclusion that backbonding is significant in these compounds – as large or even larger than in the corresponding phosphane complexes. This is partly due to the very strong σ‐donor nature of the ligand, which makes typical metal acceptor centers very electron‐rich and hence very apt to undergo backbonding.
Synthesis, Structures, and Transfer Hydrogenation Catalysis of Bifunctional Iridium Complexes Bearing a C–N Chelate Oxime Ligand
Authors: Watanabe Megumi , Kashiwame Yohei , Kuwata Shigeki , Ikariya Takao
Published: October 2011

We have synthesized a series of organometallic oxime complexes as novel metal–ligand cooperating bifunctional catalysts. The reaction of [{Cp*IrCl(μ2‐Cl)}2] with ketoximes in the presence of sodium acetate afforded the half‐sandwich chlorido iridium complexes 6 bearing a C–N chelate oxime ligand with a protic OH group in the β‐position to the metal. Complex 6a, derived from acetophenone oxime, reacted with silver triflate to give the triflate complex 7 and cationic nitrile complex 8 depending upon the reaction solvent. Complexes 6 also reacted with a base in dichloromethane to afford the oximato‐bridged dinuclear complexes 9, which were converted back to the chlorido complexes 6 upon treatment with an amine hydrochloride. In contrast, dehydrochlorination of 6 in 2‐propanol as well as the reaction of 9 with 2‐propanol yielded the hydrido‐bridged dinuclear oxime–oximato complexes 10. Crossover experiments revealed that 10 dissociates into the mononuclear hydrido–oxime complex 11 and unsaturated oximato complex 12, which are interconvertible by reactions with hydrogen donors and acceptors. Owing to the metal–ligand cooperation, 10 effectively catalyzed transfer hydrogenation of ketones with 2‐propanol.
Absorption difference between diacylglycerol oil and butter blend containing diacylglycerol oil
Authors: Kristensen Janni Brogaard , Jørgensen Henry , Mu Huiling
Published: October 2011

This study aims at investigating whether the intake of butter blends containing diacylglycerol (DAG) oil may result in reduced fat accumulation, in similarity to DAG oil, and the potential metabolic differences between butter blends and DAG oil. Four experimental diets containing either 10 wt% DAG butter blend (BDAG), triacylglycerol (TAG) butter blend (BTAG), DAG oil (ODAG) or TAG oil (OTAG) were prepared, and each was fed to a group of 8 male Wistar rats. The design of the experiment was a combined balance and feeding experiment. The rats fed the BTAG and ODAG‐diets had a significantly higher protein content than rats fed the BDAG and OTAG‐diets, and the fat content was significantly lower in rats fed the ODAG‐diet as compared to rats fed the OTAG and BDAG‐diets. A significantly higher content of ash was observed in rats fed the two TAG diets. The ratio of abdominal fat weight/body weight was significantly higher for rats fed the BDAG‐diet than for rats fed the BTAG and ODAG‐diets. To conclude, the beneficial effects of DAG oil in reducing body fat accumulation cannot be observed in DAG oil containing butter blends, and the effect of DAG on bone health requires further investigation.
Lewis Acid‐Catalyzed Selective Synthesis of Diversely Substituted Indolo‐ and Pyrrolo[1,2‐a]quinoxalines and Quinoxalinones by Modified Pictet–Spengler Reaction
Authors: Verma Akhilesh K. , Jha Rajeev R. , Sankar V. Kasi , Aggarwal Trapti , Singh Rajendra P. , Chandra Ramesh
Published: October 2011

An efficient tandem process for the selective synthesis of 1,2‐annulated α‐fused quinoxalines using benzotriazole methodology by a modified Pictet–Spengler reaction is described. The approach involves the reaction of arylamines 4 with aromatic aldehydes 5 to furnish 6‐endo‐dig‐cyclized products. Dihydroquinoxalines 6 were selectively obtained by using AlCl3 in tetrahydrofuran (THF) at room temperature for two hours. However, after ten hours, quinoxalines 7 were obtained exclusively in excellent yields. A series of biologically important fluoro‐ and piperazenyl‐substituted quinoxalines were also synthesized. This developed methodology also provides access to a novel tandem synthesis of quinoxalinones 9.
Ritter Reaction: Recent Catalytic Developments
Authors: Guérinot Amandine , Reymond Sébastien , Cossy Janine
Published: October 2011

The Ritter reaction is a method of choice for the production of amides, which are versatile intermediates in organic synthesis and compounds of interest in natural product synthesis. Recent efforts have been directed towards the development of catalytic versions for the development of more eco‐friendly synthetic routes to amides. This review summarizes the recent progress in this area and covers new applications in the field of Ritter‐type and multicomponent reactions.
Application of Proline‐Functionalised 1,2‐Diphenylethane‐1,2‐diamine (DPEN) in Asymmetric Transfer Hydrogenation of Ketones
Authors: Manville Charles V. , Docherty Gordon , Padda Ranbir , Wills Martin
Published: October 2011

A series of enantiomerically pure ligands containing a combination of proline and DPEN groups have been prepared and employed in the asymmetric transfer hydrogenation of ketones. In the case of cyclic ketones, alcohols with ee values of up to 98 % were obtained.
Selective Synthesis of Fused 1,4‐ and 1,2‐Dihydropyridines by Domino Reactions of Arylamines, Acetylenedicarboxylate, Aldehydes, and Cyclic 1,3‐Diketones
Authors: Sun Jing , Sun Yan , Gao Hong , Yan Chao‐Guo
Published: October 2011

A practical procedure for the preparation of fused 1,4‐dihydropyridines was developed through the domino four‐component reactions of arylamines, acetylenedicarboxylate, aromatic aldehydes, and cyclic 1,3‐diketones in acetic acid. Unusual fused 1,2‐dihydropyridines can also be efficiently prepared by controlling the reaction conditions.
Insulin biosynthesis in neuronal progenitors derived from adult hippocampus and the olfactory bulb
Authors: Kuwabara Tomoko , Kagalwala Mohamedi N. , Onuma Yasuko , Ito Yuzuru , Warashina Masaki , Terashima Kazuyuki , Sanosaka Tsukasa , Nakashima Kinichi , Gage Fred H. , Asashima Makoto
Published: October 2011

In the present study, we demonstrated that insulin is produced not only in the mammalian pancreas but also in adult neuronal cells derived from the hippocampus and olfactory bulb (OB). Paracrine Wnt3 plays an essential role in promoting the active expression of insulin in both hippocampal and OB‐derived neural stem cells. Our analysis indicated that the balance between Wnt3, which triggers the expression of insulin via NeuroD1, and IGFBP‐4, which inhibits the original Wnt3 action, is regulated depending on diabetic (DB) status. We also show that adult neural progenitors derived from DB animals retain the ability to give rise to insulin‐producing cells and that grafting neuronal progenitors into the pancreas of DB animals reduces glucose levels. This study provides an example of a simple and direct use of adult stem cells from one organ to another, without introducing additional inductive genes.

See accompanying article http://dx.doi.org/10.1002/emmm.201100178
Equivalent mechanical models of sloshing fluid in arbitrary‐section aqueducts
Authors: Li Yuchun , Di Qingshuang , Gong Yongqing
Published: October 2011

This paper reports on a semi‐analytical/numerical method to model sloshing water in an arbitrarily shaped aqueduct. The water motion is assumed to be inviscid, compressible, and linear (small displacement). The transverse sloshing fluid in an aqueduct is equivalently simplified as a fixed rigid mass M0 and a mass–spring system (M1, K1). According to a rule that the actual fluid (computed with finite element model) and its equivalent mechanical model have the same first sloshing frequency and acting effects on the aqueduct, the analytical solutions of the fixed (impulsive) mass M0, sloshing (convective) massM1, spring stiffness K1, and their locations in the aqueduct body are acquired by the least squares (curve fitting) algorithm. Applying this equivalent principle, the equivalent mechanical models are respectively obtained for the sloshing water in rectangular, semicircular, U‐shaped, and trapezoid aqueducts. The equivalent principle and fluid models are validated through comparison investigations involving rectangular and U‐shaped aqueducts. The dynamic properties and seismic responses of the original and equivalent systems are simulated, compared, and discussed for a U‐shaped aqueduct bridge. The main purpose of this paper is to provide a simplified model of sloshing fluid for the seismic/wind‐resistant computation of the support structures of the aqueduct bridge. Copyright © 2011 John Wiley & Sons, Ltd.
Coupling of finite volume method and thermal lattice Boltzmann method and its application to natural convection
Authors: Luan H.B. , Xu H. , Chen L. , Feng Y.L. , He Y.L. , Tao W.Q.
Published: October 2011

On the basis of the existing density distribution function reconstruction operator, the temperature distribution operator was derived to calculate heat transfer by coupling the lattice Boltzmann method (LBM) with the finite volume method. The present coupling model was validated by two‐dimensional natural convection flows with and without an isolated internal vertical plate. The results from the coupling model agree well with those from the pure‐finite volume method, pure‐LBM and references, and all the physical quantities cross the coupled interface smoothly. On the basis of residual history curves, it is likely that the convergence property and the numerical stability of the present model are better than those of the pure‐LBM at fine grid numbers and high Rayleigh numbers. Copyright © 2011 John Wiley & Sons, Ltd.
Altered store operated calcium entry increases cyclic 3′,5′-adenosine monophosphate production and extracellular signal-regulated kinases 1 and 2 phosphorylation in polycystin-2-defective cholangiocytes
Authors: Spirli Carlo , Locatelli Luigi , Fiorotto Romina , Morell Carola M. , Fabris Luca , Pozzan Tullio , Strazzabosco Mario
Published: October 2011

Mutations in polycystins (PC1 or PC2/TRPP2) cause progressive polycystic liver disease (PLD). In PC2-defective mice, cyclic 3′,5′-adenosine monophosphate/ protein kinase A (cAMP/PKA)-dependent activation of extracellular signal-regulated kinase/ mammalian target of rapamycin (ERK-mTOR) signaling stimulates cyst growth. We investigated the mechanisms connecting PC2 dysfunction to altered Ca2+ and cAMP production and inappropriate ERK signaling in PC2-defective cholangiocytes. Cystic cholangiocytes were isolated from PC2 conditional-KO (knockout) mice (

Pkd2flox/−:pCxCreER

™; hence, called Pkd2KO) and compared to cholangiocytes from wild-type mice (WT). Our results showed that, compared to WT cells, in PC2-defective cholangiocytes (Pkd2KO), cytoplasmic and ER-Ca2+ (measured with Fura-2 and Mag-Fluo4) levels are decreased and store-operated Ca2+ entry (SOCE) is inhibited, whereas the expression of Ca2+-sensor stromal interaction molecule 1 (STIM1) and store-operated Ca2+ channels (e.g., the Orai1 channel) are unchanged. In Pkd2KO cells, ER-Ca2+ depletion increases cAMP and PKA-dependent ERK1/2 activation and both are inhibited by STIM1 inhibitors or by silencing of adenylyl cyclase type 6 (AC6).

Conclusion :

These data suggest that PC2 plays a key role in SOCE activation and inhibits the STIM-dependent activation of AC6 by ER Ca2+ depletion. In PC2-defective cells, the interaction of STIM-1 with Orai channels is uncoupled, whereas coupling to AC6 is maximized. The resulting overproduction of cAMP, in turn, potently activates the PKA/ERK pathway. PLD, because of PC2 deficiency, represents the first example of human disease linked to the inappropriate activation of store-operated cAMP production.
Ethnicity and nonalcoholic fatty liver disease
Authors: Bambha Kiran , Belt Patricia , Abraham Maria , Wilson Laura A. , Pabst Mark , Ferrell Linda , Unalp-Arida Aynur , Bass Nathan
Published: October 2011

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder in the United States; however, few data are available about racial and ethnic variation. We investigated relationships between ethnicity, NAFLD severity, metabolic derangements, and sociodemographic characteristics in a well-characterized cohort of adults with biopsy-proven NAFLD. Data were analyzed from 1,026 adults (≥18 years) in the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) from 2004 to 2008, for whom liver histology data were available within 6 months of enrollment. Associations between ethnicity (i.e., Latino versus non-Latino white) and NAFLD severity (i.e., NASH versus non-NASH histology and mild versus advanced fibrosis) were explored with multiple logistic regression analysis. We also investigated effect modification of ethnicity on metabolic derangements for NAFLD severity. Within the NASH CRN, 77% (N = 785) were non-Latino white and 12% (N = 118) were Latino. Sixty-one percent (N = 628) had NASH histology and 28% (N = 291) had advanced fibrosis. Latinos with NASH were younger, performed less physical activity, and had higher carbohydrate intake, compared to non-Latino whites with NASH. Gender, diabetes, hypertension, hypertriglyceridemia, aspartate aminotransferase (AST), platelets, and the homeostasis model assessment of insulin resistance (HOMA-IR) were significantly associated with NASH. Age, gender, AST, alanine aminotransferase, alkaline phosphatase, platelets, total cholesterol, hypertension, and HOMA-IR, but not ethnicity, were significantly associated with advanced fibrosis. The effect of HOMA-IR on the risk of NASH was modified by ethnicity: HOMA-IR was not a significant risk factor for NASH among Latinos (odds ratio [OR] = 0.93; 95% confidence interval [CI]: 0.85-1.02), but was significant among non-Latino whites (OR, 1.06; 95% CI: 1.01-1.11).

Conclusion:

Metabolic risk factors and sociodemographic characteristics associated with NASH differ by ethnicity. Additional insights into NASH pathogenesis may come from further studies focused on understanding ethnic differences in this disease.
Association of Coffee and Caffeine Consumption With Fatty Liver Disease, Nonalcoholic Steatohepatitis, and Degree of Hepatic Fibrosis
Authors: Molloy Jeffrey W. , Calcagno Christopher J. , Williams Christopher D. , Jones Frances J. , Torres Dawn M. , Harrison Stephen A.
Published: October 2011

Coffee caffeine consumption (CC) is associated with reduced hepatic fibrosis in patients with chronic liver diseases, such as hepatitis C. The association of CC with nonalcoholic fatty liver disease (NAFLD) has not been established. The aim of this study was to correlate CC with the prevalence and severity of NAFLD. Patients involved in a previously published NAFLD prevalence study, as well as additional NASH patients identified in the Brooke Army Medical Center Hepatology clinic, were queried about their caffeine intake. A validated questionnaire for CC was utilized to assess for a relationship between caffeine and four groups: ultrasound negative (controls), bland steatosis/not-NASH, NASH stage 0-1, and NASH stage 2-4. A total of 306 patients responded to the CC questionnaire. Average milligrams of total caffeine/coffee CC per day in controls, bland steatosis/not-NASH, NASH stage 0-1, and NASH stage 2-4 were 307/228, 229/160, 351/255, and 252/152, respectively. When comparing patients with bland steatosis/not-NASH to those with NASH stage 0-1, there was a significant difference in CC between the two groups (

P

= 0.005). Additionally, when comparing patients with NASH stage 0-1 to those with NASH stage 2-4, there was a significant difference in coffee CC (

P

= 0.016). Spearman's rank correlation analysis further supported a negative relationship between coffee CC and hepatic fibrosis (r = −0.215;

P

= 0.035).

Conclusion:

Coffee CC is associated with a significant reduction in risk of fibrosis among NASH patients. (Hepatology 2012)
Antagonism of peripheral hepatic cannabinoid receptor-1 improves liver lipid metabolism in mice: Evidence from cultured explants
Authors: Jourdan Tony , Demizieux Laurent , Gresti Joseph , Djaouti Louiza , Gaba Lila , Vergès Bruno , Degrace Pascal
Published: October 2011

It is well established that inactivation of the central endocannabinoid system (ECS) through antagonism of cannabinoid receptor 1 (CB1R) reduces food intake and improves several pathological features associated with obesity, such as dyslipidemia and liver steatosis. Nevertheless, recent data indicate that inactivation of peripheral CB1R could also be directly involved in the control of lipid metabolism independently of central CB1R. To further investigate this notion, we tested the direct effect of the specific CB1R antagonist, SR141716, on hepatic carbohydrate and lipid metabolism using cultured liver slices. CB1R messenger RNA expression was strongly decreased by SR141716, whereas it was increased by the CB1R agonist, arachidonic acid N-hydroxyethylamide (AEA), indicating the effectiveness of treatments in modulating ECS activity in liver explants both from lean or

ob/ob

mice. The measurement of O2 consumption revealed that SR141716 increased carbohydrate or fatty acid utilization, according to the cellular hormonal environment. In line with this, SR141716 stimulated ß-oxidation activity, and the role of CB1R in regulating this pathway was particularly emphasized when ECS was hyperactivated by AEA and in

ob/ob

tissue. SR141716 also improved carbohydrate and lipid metabolism, blunting the AEA-induced increase in gene expression of proteins related to lipogenesis. In addition, we showed that SR141716 induced cholesterol

de novo

synthesis and high-density lipoprotein uptake, revealing a relationship between CB1R and cholesterol metabolism.

Conclusion:

These data suggest that blocking hepatic CB1R improves both carbohydrate and lipid metabolism and confirm that peripheral CB1R should be considered as a promising target to reduce cardiometabolic risk in obesity.
The Adjustment of Ethnic Minority and Majority Children Living in Israel: Does Parental Use of Corporal Punishment Act as a Mediator?
Authors: Regev Rotem , Gueron‐Sela Noa , Atzaba‐Poria Naama
Published: October 2011

This paper examines explanatory mechanisms of differences, in both positive and negative aspects of children's adjustment, between ethnic minority (i.e., Former Soviet Union—FSU origin) and ethnic majority (i.e., Israeli) children living in Israel. Seventy Israeli children (40 girls) and 75 FSU origin children (38 girls) and their parents constituted the study sample. Both mothers and fathers reported on the children's prosocial and externalizing behaviours and provided accounts of their use of corporal punishment. Analyses showed that FSU origin children displayed lower levels of prosocial behaviour as well as higher levels of externalizing problems and that their parents used more corporal punishment than their Israeli counterparts. In addition, a mediation model was determined in which both maternal and paternal use of corporal punishment mediated the link between ethnicity and the child's prosocial behaviour. Furthermore, according to the best fitting structural equation model, ethnicity did not have a direct effect on children's prosocial behaviour. This link was fully mediated by maternal and paternal corporal punishment. No mediation was revealed for the links between ethnicity and externalizing problems. The process of risk is discussed. Copyright © 2011 John Wiley & Sons, Ltd.
HIF-1α and HIF-2α degradation is differentially regulated in nucleus pulposus cells of the intervertebral disc
Authors: Fujita Nobuyuki , Chiba Kazuhiro , Shapiro Irving M , Risbud Makarand V
Published: October 2011

Studies of many cell types show that levels of hypoxia inducible factor (HIF)-1α and HIF-2α are primarily controlled by oxygen-dependent proteasomal degradation, catalyzed by HIF prolyl-hydroxylases (PHDs). However, in the hypoxic niche of the intervertebral disc, the mechanism of HIF-α turnover in nucleus pulposus cells is not yet known. We show that in nucleus pulposus cells HIF-1α and HIF-2α, degradation was mediated through 26S proteasome irrespective of oxygen tension. It is noteworthy that HIF-2α degradation through 26S proteasome was more pronounced in hypoxia. Surprisingly, treatment with DMOG, a PHD inhibitor, shows the accumulation of only HIF-1α and induction in activity of its target genes, but not of HIF-2α. Loss and gain of function analyses using lentiviral knockdown of PHDs and overexpression of individual PHDs show that in nucleus pulposus cells only PHD2 played a limited role in HIF-1α degradation; again HIF-2α degradation was unaffected. We also show that the treatment with inhibitors of lysosomal proteolysis results in a strong accumulation of HIF-1α and to a much smaller extent of HIF-2α levels. It is thus evident that in addition to PHD2 catalyzed degradation, the HIF-1α turnover in nucleus pulposus cells is primarily regulated by oxygen-independent pathways. Importantly, our data clearly suggests that proteasomal degradation of HIF-2α is not mediated by a classical oxygen-dependent PHD pathway. These results for the first time provide a rationale for the normoxic stabilization as well as the maintenance of steady-state levels of HIF-1α and HIF-2α in nucleus pulposus cells. © 2012 American Society for Bone and Mineral Research
The antioxidant tempol ameliorates arterial medial calcification in uremic rats: Important role of oxidative stress in the pathogenesis of vascular calcification in chronic kidney disease
Authors: Yamada Shunsuke , Taniguchi Masatomo , Tokumoto Masanori , Toyonaga Jiro , Fujisaki Kiichiro , Suehiro Takaichi , Noguchi Hideko , Iida Mitsuo , Tsuruya Kazuhiko , Kitazono Takanari
Published: October 2011

Vascular calcification is closely related to cardiovascular morbidity and mortality. Accumulating data indicate that oxidative stress is associated with dysfunction of various organs, including cardiovascular diseases in chronic kidney disease (CKD). However, it remains undetermined if oxidative stress induced by uremia promotes arterial medial calcification. The present study investigated the role of oxidative stress in the pathogenesis of arterial medial calcification in uremic rats. Rats with uremia induced by adenine-rich diet progressively developed arterial medial calcification, which was accompanied by time-dependent increases in both aortic and systemic oxidative stress. Immunohistochemical and biochemical analyses showed that the arterial medial calcification progressed in a time-dependent manner that is parallel to the osteogenic transdifferentiation of vascular smooth muscle cells. Accumulation of oxidative stress was also identified in the calcified regions. Time-course studies indicated that both oxidative stress and hyperphosphatemia correlated with arterial medial calcification. Tempol, an antioxidant, ameliorated osteogenic transdifferentiation of vascular smooth muscle cells and arterial medial calcification in uremic rats, together with reduction in aortic and systemic oxidative stress levels, without affecting serum biochemical parameters. Our data suggest that oxidative stress induced by uremia can play a role in the pathogenesis of vascular calcification in CKD, and that antioxidants such as tempol are potentially useful in preventing the progression of vascular calcification in CKD. © 2012 American Society for Bone and Mineral Research
Adverse effects of hyperlipidemia on bone regeneration and strength
Authors: Pirih Flavia , Lu Jinxiu , Ye Fei , Bezouglaia Olga , Atti Elisa , Ascenzi Maria-Grazia , Tetradis Sotirios , Demer Linda , Aghaloo Tara , Tintut Yin
Published: October 2011

Hyperlipidemia increases the risk for generation of lipid oxidation products, which accumulate in the subendothelial spaces of vasculature and bone. Atherogenic high-fat diets increase serum levels of oxidized lipids, which are known to attenuate osteogenesis in culture and to promote bone loss in mice. In this study, we investigated whether oxidized lipids affect bone regeneration and mechanical strength. Wild-type (WT) and hyperlipidemic (Ldlr−/−) mice were placed on a high-fat (HF) diet for 13 weeks. Bilateral cranial defects were introduced on each side of the sagittal suture, and 5 weeks postsurgery on the respective diets, the repair/regeneration of cranial bones and mechanical properties of femoral bones were assessed. MicroCT and histological analyses demonstrated that bone regeneration was significantly impaired by the HF diet in WT and Ldlr−/− mice. In femoral bone, cortical bone volume fraction (bone volume [BV]/tissue volume [TV]) was significantly reduced, whereas cortical porosity was increased by the HF diet in Ldlr−/− but not in WT mice. Femoral bone strength and stiffness, measured by three-point bending analysis, were significantly reduced by the HF diet in Ldlr−/−, but not in WT mice. Serum analysis showed that the HF diet significantly increased levels of parathyroid hormone, tumor necrosis factor (TNF)-α, calcium, and phosphorus, whereas it reduced procollagen type I N-terminal propeptide, a serum marker of bone formation, in Ldlr−/−, but not in WT mice. The serum level of carboxyl-terminal collagen crosslinks, a marker for bone resorption, was also 1.7-fold greater in Ldlr−/− mice. These findings suggest that hyperlipidemia induces secondary hyperparathyroidism and impairs bone regeneration and mechanical strength. © 2012 American Society for Bone and Mineral Research
A nonsynonymous TNFRSF11A variation increases NFκB activity and the severity of Paget's disease
Authors: Gianfrancesco Fernando , Rendina Domenico , Di Stefano Marco , Mingione Alessandra , Esposito Teresa , Merlotti Daniela , Gallone Salvatore , Magliocca Sara , Goode Alice , Formicola Daniela , Morello Giovanna , Layfield Robert , Frattini Annalisa , De Filippo Gianpaolo , Nuti Ranuccio , Searle Mark , Strazzullo Pasquale , Isaia Giancarlo , Mossetti Giuseppe , Gennari Luigi
Published: October 2011

Mutations in the SQSTM1 gene were identified as a common cause of Paget's disease of bone (PDB) but experimental evidence demonstrated that SQSTM1 mutation is not sufficient to induce PDB in vivo. Here, we identified two nonsynonymous single nucleotide polymorphisms (SNPs) (C421T, H141Y and T575C, V192A) in the TNFRSF11A gene, associated with PDB and with the severity of phenotype in a large population of 654 unrelated patients that were previously screened for SQSTM1 gene mutations. The largest effect was found for the T575C variant, yielding an odds ratio of 1.29 (p = 0.003), with the C allele as the risk allele. Moreover, an even more significant p-value (p = 0.0002) was observed in the subgroup of patients with SQSTM1 mutation, with an odds ratio of 1.71. Interestingly, patients with the C allele also showed an increased prevalence of polyostotic disease (68%, 53%, and 51% in patients with CC, CT, and TT genotypes, respectively; p = 0.01), as well as an increased number of affected skeletal sites (2.9, 2.5, and 2.0 in patients with CC, CT, and TT genotypes, respectively, p = 0.008). These differences increased when analyses were restricted to cases with SQSTM1 mutation. In human cell lines, cotrasfection with mutated SQSTM1 and TNFRSF11AA192 produced a level of activation of NFκB signaling greater than cotrasfection with wild-type SQSTM1 and TNFRSF11AV192, confirming genetics and clinical evidences. These results provide the first evidence that genetic variation within the OPG/RANK/RANKL system influences the severity of PBD in synergistic action with SQSTM1 gene mutations. © 2012 American Society for Bone and Mineral Research
Molecular imprinting in monolayer surfaces
Authors: Balamurugan Subramanian , Spivak David A.
Published: October 2011

A comprehensive report on molecularly imprinted monolayers (MIMs) is presented, but does not include bulk‐polymer thin film coatings on surfaces, inorganic surface imprinting, polymer grafting and layer‐by‐layer methods. Due to difficulties in imprinting large molecules and obtaining fast binding responses with traditional network polymer materials, MIMs have been developed with the aim of enhancing mass‐transfer of analytes in imprinted materials. Three approaches to MIM fabrication have been developed with respect to the formation of the pre‐organized template‐matrix complex. In the first approach, the molecular binding sites are formed in a monolayer on a glass or gold surface. The second approach uses a template‐macromolecule complex to form binding sites in the solution phase that are immobilized onto a surface; and the third approach transfers an imprinted Langmuir film onto a gold surface. Mass transfer in these MIMs in most cases is on the order of minutes, and both small and large molecules (proteins) have been imprinted. Copyright © 2011 John Wiley & Sons, Ltd.
DCE‐MRI model selection for investigating disruption of microvascular function in livers with metastatic disease
Authors: Banerji Anita , Naish Josephine H. , Watson Yvonne , Jayson Gordon C. , Buonaccorsi Giovanni A. , Parker Geoffrey J.M.
Published: October 2011

Purpose:

To evaluate the Akaike information criterion (AIC) model selection technique as a method for detecting differences in microvascular characteristics between tumorous and non‐tumor liver tissue.

Materials and Methods:

The AIC was applied to six patient datasets with liver metastases to determine, on a per voxel basis, which of two physiologically plausible candidate models gave a more appropriate description of the data. The dual‐input single‐compartment Materne model, extended to incorporate a novel portal input function estimation method, was chosen to represent liver tissue and the single‐input dual‐compartment extended Kety model was used for tumor.

Results:

Median AIC probabilities when comparing tumor versus liver and tumor versus tumor‐margins were significantly different (P ≤ 0.01) in five of the six patient datasets. Comparisons between tumor margins and liver regions were significantly different in four datasets. Median AIC probabilities selected for the extended Kety model in all tumor regions, with the Materne model being progressively more probable through tumor margins into liver.

Conclusion:

We present a viable method for assessing the spatially varying microvascular characteristics of tumor‐bearing livers, with possible applications in lesion detection, assessment of tumor invasion, and measurement of drug efficacy. J. Magn. Reson. Imaging 2012;35:196‐203. © 2011 Wiley Periodicals, Inc.
Storage induced changes to high protein powders: influence on surface properties and solubility
Authors: Fyfe Kim N , Kravchuk Olena , Le Thao , Deeth Hilton C , Nguyen Anh V , Bhandari Bhesh
Published: October 2011

BACKGROUND: MPC 80 is a high‐protein (80%) milk powder commonly used in the food industry as a functional ingredient and valued for its nutritional quality. However, its rehydration properties decline during storage, causing more time to be required for rehydration of the powder by the end user. It is thought that changes at the surface of the powder particles contribute to this reduced solubility during storage.

RESULTS: Surface composition and structural changes in milk protein concentrate (MPC) were observed during 90 days of storage at temperatures of 25 and 40 °C and relative humidities of 44, 66 and 84%. No significant changes to the surface composition (fat, protein and lactose) of the MPC powder samples occurred during storage; however, some changes in the microstructure of the powders were observed. Scanning electron microscopy analysis of the powder particles during dissolution showed the formation of a crust, consisting of a thin layer of fused casein micelles, on the surface of the stored powders. An increase in the hydrophobicity at the surface of the particles was evident by X‐ray photoelectron spectroscopy analysis of the bonding state of the elements at or near the surface and by atomic force microscopy measurements of the adherence of particles to the surface of a material.

CONCLUSION: The development of this ‘crust’ is thought to contribute to the decrease in the solubility of the powder particles during storage. The increase in the hydrophobicity at the surface and the casein micelle interactions resulting in the surface crust formation appear to contribute to the decrease in the solubility of MPC during storage. Copyright © 2011 Society of Chemical Industry
Prevention of lymphocele in female pelvic lymphadenectomy by a collagen patch coated with the human coagulation factors: A pilot study
Authors: Tinelli Andrea , Giorda Giorgio , Manca Corrado , Pellegrino Marcello , Prudenzano Raffaele , Guido Marcello , Dell'edera Domenico , Malvasi Antonio
Published: October 2011

Background and Objectives

The prevention of lymphoceles was tested using collagen patch coated with the human coagulation factors (TachoSil) on 58 consecutive patients with endometrial cancer who had undergone hysterectomy and pelvic lymphadenectomy (PL).

Methods

Patients were randomized in two groups: standard technique plus TachoSil (30 patients, group 1) and standard technique only (28, group 2). All surgical parameters were collected and patients underwent ultrasound examination on postoperative days 7, 14, and 28. The main outcome measures were: the development of symptomatic or asymptomatic lymphoceles, the need for further surgical intervention, as adverse effect of surgery and the drainage volume and duration.

Results

Same number of lymph nodes in both groups was removed; group 1 showed a lower drainage volume. Lymphoceles developed in 7 patients in group 1 and 16 in group 2, but only 3 were symptomatic in group 1 and 9 symptomatic in group 2, with statistical difference. Percutaneous drainage proved necessary in five cases: only one was in group 1 and four in group 2.

Conclusions

Intraoperative application of TachoSil reduced rate of postoperative lymphocysts after PL, and it seems to provide a useful additional treatment option for reducing drainage volume and preventing lymphocele development after PL. J. Surg. Oncol. 2012; 105:835–840. © 2011 Wiley Periodicals, Inc.
Impact of venous systemic oxygen persufflation supplemented with nitric oxide gas on cold-stored, warm ischemia–damaged experimental liver grafts
Authors: Srinivasan Pramod Kadaba , Yagi Shintaro , Doorschodt Benedict , Nagai Kazuyuki , Afify Mamdouh , Uemoto Shinji , Tolba Rene
Published: October 2011

The increasing shortage of donor organs has led to the increasing use of organs from non–heart-beating donors. We aimed to assess the impact of venous systemic oxygen persufflation (VSOP) supplemented with nitric oxide (NO) gas during the cold storage (CS) of warm ischemia (WI)–damaged experimental liver grafts. Rat livers (n = 5 per group) were retrieved after 30 minutes of WI induced by cardiac arrest (the WI group) and were thereafter preserved for 24 hours by CS in histidine tryptophan ketoglutarate solution. During CS, gaseous oxygen was insufflated via the caval vein with 40 ppm NO (the VSOP-NO group) or without NO (the VSOP group). Cold-stored livers without WI served as controls. Liver viability was assessed after the preservation period by normothermic isolated reperfusion for 45 minutes with oxygenated Krebs-Henseleit buffer. After 45 minutes of reperfusion, the VSOP-NO–treated livers showed significantly lower alanine aminotransferase values than the WI-damaged livers (10.2 ± 0.2 versus 78.2 ± 14.6 IU/L), whereas the control livers showed no differences from the VSOP-NO–treated livers. The mitochondrial enzyme release was lower in the VSOP-NO group (4.0 ± 0.7 IU/L) versus the WI group (18.2 ± 4.9 IU/L). An increased portal vein pressure was observed throughout reperfusion (45 minutes) in the WI group (21.7 ± 0.2 mm Hg) versus the VSOP-NO group (12.2 ± 0.8 mm Hg) and the control group (19.9 ± 0.4 mm Hg). Furthermore, the NO concentration in the perfusate after 5 minutes of reperfusion was highest in the VSOP-NO group. The release of malondialdehyde into the perfusate was significantly reduced in the VSOP-NO group (0.9 ± 0.1 nmol/mL) versus the WI group (31.3 ± 5.3 nmol/mL). In conclusion, the resuscitation of livers after 30 minutes of WI to a level comparable to that of nonischemically damaged livers is possible with VSOP supplemented with NO gas. Moreover, the application of VSOP with NO minimizes the extent of injuries caused by oxygen free radicals during preservation. Liver Transpl 18:219–225, 2012. © 2011 AASLD.
Improving the function of liver grafts exposed to warm ischemia by the leuven drug protocol: Exploring the molecular basis by microarray
Authors: Vekemans Katrien , Monbaliu Diethard , Balligand Erika , Heedfeld Veerle , Jochmans Ina , Pirenne Jacques , van Pelt Jos
Published: October 2011

Livers exposed to warm ischemia (WI) before transplantation are at risk for primary nonfunction (PNF), graft dysfunction, and ischemic biliary strictures, all associated with ischemia/reperfusion injury (IRI). Our multifactorial approach, Leuven drug protocol (LDP), has been shown to reduce these effects and increase recipient survival in WI/IRI-damaged porcine liver transplantation. The aim was the identification of the molecular mechanisms responsible for the hepatoprotective effects of the LDP. Porcine livers were exposed to 45 minutes of WI, cold-stored for 4 hours, transplanted, and either modulated (LDP group; n = 3) or not modulated (control group; n = 4). In the LDP group, the donor livers were flushed with streptokinase and epoprostenol before cold perfusion; the recipients received intravenous glycine, a-1-acid-glycoprotein, FR167653 (a mitogen-activated protein kinase inhibitor), a-tocopherol, glutathione, and apotransferrin. Liver samples were taken before WI and 1 hour after reperfusion. Gene expression was determined with microarrays and molecular pathways and key regulatory genes were identified. The number of genes changed between baseline and 1 hour after reperfusion was 686 in the LDP group and 325 in the control group. The extra genes in the LDP group belonged predominantly to pathways related to cytokine activity, apoptosis, and cell proliferation. We identified 7 genes that were suppressed in the LDP group. These genes could be linked in part to the administered drugs. New potential drug targets were identified on the basis of genes induced in the control group but unaffected in the LDP group and interactions predicted by the literature. In conclusion, the LDP primarily resulted in the suppression of inflammation-regulating genes in IRI. Furthermore, the microarray technique helped us to identify additional gene targets. Liver Transpl 18:206–218, 2012. © 2011 AASLD.